Perioperative management of severe anorexia nervosa.

As the prevalence of anorexia nervosa (AN) increased, surgery in severe AN patients also increased in the 2000s. We experienced a surgical case of a patient with severe AN, showing an extremely low BMI of 8.6 kg m(-2). We investigated the problems associated with this case and propose criteria to manage severe AN. We endeavour to report on the perioperative management of rare and severe symptoms and surgical indications of severely malnourished patients. All published reports were identified through comprehensive searches using PubMed, BioMedLib, and the Japan Medical Abstracts Society with the following terms and keywords: 'anorexia nervosa', 'eating disorder', 'hypoglycaemia', 'leucocytopaenia', 'gelatinous bone marrow', 'surgery', and 'operation'. In cases of AN with a BMI under 13 kg m(-2), marked hypoglycaemia, leucocytopaenia <3.0×10(9) litre(-1), or both, potentially fatal complications frequently occur. Accordingly, patients need strict nutritional support to avoid re-feeding syndrome until surgery. During the course of anaesthesia, careless loading of glucose or catecholamine may lead to disturbance of electrolytes or fatal arrhythmia. Intensive care and early feeding as soon as possible after surgery are important to prevent surgical site infection. Although not many perioperative cases of AN have been reported, clinicians must be aware of the danger and the causes of mortality in critical cases. Thus, the decision to undertake surgery must be taken carefully and close perioperative coordination among physicians, surgeons, psychiatrists, anaesthesiologists, and intensivists is essential.


Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to general anesthesia.

Intraoperative blood loss during spinal surgery was decreased in patients who received remifentanil as an opioid adjuvant, possibly because of lower intraoperative BP. A larger-scale prospective randomized controlled trial is warranted to confirm our results and to test whether remifentanil can decrease intraoperative blood loss during other surgical procedures.

The remifentanil group exhibited significantly lower intraoperative arterial BP than the fentanyl group. Intraoperative blood loss was also significantly lower in the remifentanil group (125 ± 67 mL vs. 165 ± 82 mL, P = 0.035).


Cardioprotective effects of hyperkalemia during smulated ischemia/reperfusion in neonatal rat cardiomyocytes - Preservation of Na+/K+-ATPase activity -

Hyperkalemia has multimodal effects on myocardial protection during ischemia/reperfusion. The preservation of Na(+)/K(+)-ATPase activity induced by hyperkalemia may have critical impact on myocardial protection. To elucidate the roles of hyperkalemia (16 mM) and Na(+)/K(+)-ATPase inhibition (100 µM ouabain) in myocardial protection during simulated ischemia (5 mM NaCN and 5.5 mM 2-deoxyglucose)/reperfusion, we measured loss of membrane integrity and bleb formation using a vital dye calcein AM in cultured neonatal rat cardiomyocytes. The control perfusate was switched to treatment solution for 15 min, followed by reperfusion for 30 min. In a second set of experiments, myocardial excitability and diastolic intracellular calcium ion concentration ([Ca(2+)]i) were measured during a 45-min treatment using a calcium-sensitive fluorescent dye fluo-4 AM. Simulated ischemia/reperfusion under ouabain treatment induced loss of membrane integrity, which was suppressed by hyperkalemia. Simulated ischemia/reperfusion induced bleb formation, which was accelerated by ouabain. Hyperkalemia delayed and inhibited the increase in diastolic [Ca(2+)]i induced by simulated ischemia. Furthermore, hyperkalemia almost completely inhibited the effects of ouabain on the diastolic [Ca(2+)]i during ischemia. These results suggest that hyperkalemia during ischemia is cardioprotective against ischemia/reperfusion insults and that hyperkalemia inhibits the effects of ouabain during ischemia.

The Journal of Medical Investigation : JMI


Recent less-invasive circulatory monitoring during renal transplantation.

For anesthetic management during renal transplantation, it is necessary to maintain the blood flow and function of the transplanted kidney by performing massive fluid management and stabilizing blood pressure. We report anesthetic management for renal transplantation with a less-invasive circulatory monitoring system (Edwards Life Sciences Co., Ltd., Irvine, California, U.S.A.). In November 2010, renal transplantation was started in our hospital, and performed in 6 patients. In the first patient, fluid/circulatory management was conducted by connecting a standard arterial line and a standard central venous (CV) line. In the second patient, a FloTrac(TM) system and a standard CV line were used. In the third patient, a standard arterial line and a PreSep(TM) CV Oximetry Catheter were used. In the fourth and fifth patients, a FloTrac(TM) and a PreSep(TM) were used. In the latest patient, FloTrac(TM) and PreSep(TM) were connected to an EV1000(TM) Clinical Platform for fluid/circulatory management. The establishment of high-visibility monitors was useful for evaluating the condition and confirming the effects. As there are marked changes in hemodynamics, the CV pressure, which has been used as a parameter of fluid management, is not reliable in renal failure patients with a high incidence of cardiovascular complications. Advances in noninvasive circulatory monitoring with dynamic indices may improve the safety of anesthetic management during renal transplantation.


Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation.

The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration.


声帯筋電図電極付き気管チューブを長時間留置し術後抜管困難をきたした1例

声帯筋電図電極付き気管チューブを長時間留置し術後抜管困難をきたした1例


Anesthetic Management with Muscle Relaxant in a Patient with Amyotrophic Lateral Sclerosis

筋萎縮性側索硬化症患者の麻酔経験

A 31-year-old woman with amyotrophic lateral sclerosis (ALS) with respiratory muscle paralysis was scheduled for tracheotomy. After applying standard neuromuscular monitoring devices, general anesthesia was induced and maintained with propofol, remifentanil, rocuronium, and sevoflurane. Sugammadex is a potent agent for reversal of neuromuscular blockade by rocuronium. The patient emerged from general anesthesia smoothly using sugammadex; however, assisted respiration was continued for possible prolongation of the effect of muscle relaxant. The postoperative course was uneventful, and she was discharged without any discomfort.


Anesthesia for Laser Surgery of a Tracheal Tumor Involving the Carina : Preservation of Spontaneous Breathing Using Remifentanil

気管分岐部腫瘍に対するレーザー焼灼術の麻酔管理 : レミフェンタニルを用いた自発呼吸温存

We describe anesthetic management of a patient with airway stenosis due to a tracheal tumor involving the carina. A 68-year-old man developed dyspnea and was scheduled for YAG laser surgery under general anesthesia. Awake fiberoptic intubation was selected for anesthesia induction, and percutaneous cardiopulmonary support (PCPS) was ready to be established prior to induction of anesthesia. Anesthesia was maintained with remifentanil (0.05 microg x kg(-1) x min(-1)) and propofol (2 mg x kg(-1) x hr(-1)), and spontaneous breathing was preserved throughout the surgical procedure. The operation was completed successfully without any adverse events, and PCPS was not used. In this patient, preservation of spontaneous breathing using remifentanil was found to be useful for airway management.


Role of the O-linked -N-acetylglucosamine in the cardioprotection induced by isoflurane.

Cardiac protection by volatile anesthetic-induced preconditioning and ischemic preconditioning have similar signaling pathways. Recently, it was reported that augmentation of protein modified with O-linked -N-acetylglucosamine (O-GlcNAc) contributes to cardiac protection. This study investigated the role of O-GlcNAc in cardiac protection induced by anesthetic-induced preconditioning. O-GlcNAc-modified proteins were visualized by immunoblotting. Tolerance against ischemia or reperfusion was tested in vivo (n = 8) and in vitro (n = 6). The opening of the mitochondrial permeability transition pore (mPTP) upon oxidative stress was examined in myocytes treated with calcein AM (n = 5). Coimmunoprecipitation and enzymatic labeling were performed to detect the mitochondrial protein responsible for the mPTP opening. Isoflurane treatment and the consequent augmentation of O-GlcNAc concentrations reduced the infarct size (26 ± 5% [mean ± SD], P < 0.001) compared with the control. The protective effect of O-GlcNAc was eliminated in the group pretreated with the O-GlcNAc transferase inhibitor alloxan (39 ± 5%, P < 0.001). Myocyte survival also showed the same result in vitro. Formation of the mPTP was abrogated in the isoflurane-treated cells (86 ± 4%, P < 0.001) compared with the control and alloxan-plus-isoflurane-treated cells (57 ± 7%, P < 0.001). Coimmunoprecipitation and enzymatic labeling studies revealed that the O-GlcNAc-modified, voltage-dependent anion channel restained the mPTP opening. Isoflurane induced O-GlcNAc modification of mitochondrial voltage-dependent anion channel. This modification inhibited the opening of the mPTP and conferred resistance to ischemia-reperfusion stress.


Molecular mechanisms of the inhibitory effects of clonidine on vascular adenosine triphosphate-sensitive potassium channels.

We investigated the effects of the imidazoline-derived α2-adrenoceptor agonist clonidine on vascular adenosine triphosphate-sensitive potassium (K(ATP)) channel activity in rat vascular smooth muscle cells and recombinant vascular K(ATP) channels transiently expressed in COS-7 cells. Using the patch-clamp method, we investigated the effects of clonidine on the following: (1) native vascular K(ATP) channels; (2) recombinant K(ATP) channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits; (3) SUR-deficient channels derived from a truncated isoform of the Kir6.2 subunit (Kir6.2ΔC36 channels); and (4) mutant Kir6.2ΔC36 channels with diminished sensitivity to ATP (Kir6.2ΔC36-K185Q channels). Clonidine (≥3 × 10(-8) M) inhibited native K(ATP) channel activity in cell-attached configurations with a half-maximal inhibitory concentration value of 1.21 × 10(-6) M and in inside-out configurations with a half-maximal inhibitory concentration value of 0.89 × 10(-6) M. With similar potency, clonidine (10(-6) or 10(-3) M) also inhibited the activities of various recombinant SUR/Kir6.0 K(ATP) channels, the Kir6.2ΔC36 channel, and the Kir6.2ΔC36-K185Q channel. Clinically relevant concentrations of clonidine inhibit K(ATP) channel activity in vascular smooth muscle cells. This inhibition seems to be the result of its effect on the Kir6.0 subunit and not on the SUR subunit.


Anesthesia for a patient with severe tracheal stenosis due to thoracic aortic aneurysm

胸部大動脈瘤により高度気管狭窄を呈した症例の麻酔経験

Tracheobronchial compression is a well-recognized complication of thoracic aortic aneurysm. We describe the anesthetic management of a patient with severe tracheal stenosis due to thoracic aortic aneurysm. An 81-year-old woman was scheduled for endovascular aortic stent graft placement. Computed tomographic (CT) scans showed that the narrowest diameter of the trachea was 3 x 18 mm. Awake fiberoptic intubation was selected for anesthesia induction, and percutaneous cardiopulmonary support (PCPS) was ready to be established prior to induction of anesthesia. We successfully inserted ID 6.0 mm spiral tube beyond the tracheal compression using bronchoscope and induced hypotension. The operation was completed successfully without any adverse events. We conclude that, in patients with thoracic aortic aneurysm, careful attention should be paid not only to circulation but to respiration.


General anesthesia for electroconvulsive therapy with Brugada electrocardiograph pattern.

Brugada syndrome is characterized by an electrocardiograph pattern of right bundle-branch block and has an increased risk for cardiac arrest due to malignant arrhythmia. We describe the successful anesthetic management for electroconvulsive therapy in a patient with Brugada electrocardiograph pattern. Patients with Brugada ECG pattern are not recommended to use neostigmine which augments ST elevation. Sugammadex was administered as a neuromuscular reversal agent in this case. Sugammadex provides rapid reversal of profound rocuronium-induced neuromuscular blockade under propofol anesthesia.

The Journal of Medical Investigation : JMI


Neurokinin-1 receptor antagonism, aprepitant, effectively diminishes post-operative nausea and vomiting while increasing analgesic tolerance in laparoscopic gynecological procedures.

Post-operative nausea and vomiting (PONV) remains the most frequently reported patient complaint after anesthesia. Aprepitant is the first neurokinin-1(NK1) receptor antagonism available for use as an antiemetic. We investigated whether aprepitant can effectively decrease PONV in patients undergoing laparoscopic gynecological surgery. Sixty four patients receiving general anesthesia for laparoscopic gynecological surgery were randomly assigned to either receive a preoperative dose of 80 mg aprepitant or no drug. Efficacy was assessed in 2 and 24 hours after surgery. Primary and secondary endpoints were analyzed for the time intervals 0-2 hours (acute phase) and 2-24 hours (delayed phase). Vomiting, nausea, use of rescue anti-emetic, and visual analog scale (VAS) were assessed. Nausea was assessed on a 4-point scale, from 0 to 3. Sixty patients participated in the study. At acute phase, PONV was present in both control and NK1 group and were 63% and 43% respectively. The severity of nausea was much less in the NK1 group. PONV prevalence at delayed phase was present in control but absent in NK1 group 27% vs. 0%, respectively. The amount of pain medication used by patients in the NK1 group was significantly less for diclofenac and pentazocine suggesting increase pain tolerance. Neurokinin-1 receptor antagonism effectively lowered PONV increased pain tolerance, and expedited recovery in patients undergoing laparoscopic gynecological surgery.

The Journal of Medical Investigation : JMI


Anesthetic management of a patient with Becker muscular dystrophy

ベッカー型筋ジストロフィ症患者の麻酔経験

We experienced anesthetic management of a patient with Becker muscular dystrophy. He had advanced dilated cardiomyopathy and high serum CK in the preoperative examinations. Anesthesia was planned to avoid triggering malignant hyperthermia or rhabdomyolysis and hemodynamic changes. Propofol, remifentanil and a minimum dose of rocuronium bromide were used for anesthetic induction and maintainance. Arterial pressure, cardiac output and stroke volume variation were monitored by Flotrac sensor. There were no adverse events observed during the anesthetic management. In conclusion, total intravenous anesthesia with the administration of rocuronium and circulatory monitoring by Flotrac sensor could be safe and efficient for anesthetic management of patients with Becker muscular dystrophy.


Anaesthesia for a patient with paraneoplastic limbic encephalitis with ovarian teratoma: relationship to anti-N-methyl-D-aspartate receptor antibodies.

Paraneoplastic limbic encephalitis associated with ovarian teratoma has recently been related to the development of antibodies to specific heteromers of the N-methyl-d-aspartate receptor and exhibits various manifestations including psychiatric symptoms, hypoventilation, seizures and derangement of autonomic nervous system function. Although recovery can sometimes occur spontaneously, early tumour resection with immunotherapy facilitates earlier recovery. Herein, we describe anaesthetic management of a 20-year-old woman who developed general convulsions and decreased level of consciousness, whom we suspected of having paraneoplastic limbic encephalitis and was scheduled for left ovarian tumour resection. Anaesthetic management was successful with no complications but the case acts as focus of discussion for the potential interaction of N-methyl-D-aspartate receptors and anaesthetic sensitivity.


Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway.

Compound K (C-K; 20-O-D-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginsenoside metabolite formed by intestinal bacteria and does not occur naturally in ginseng. In this study, we investigated whether administration of C-K has protective effects on myocardial ischemia-reperfusion injury and its potential mechanisms.


Differential effects of propofol and isoflurane on glucose utilization and insulin secretion.

Volatile anesthetics, such as isoflurane, reverse glucose-induced inhibition of pancreatic adenosine triphosphate-sensitive potassium (K(ATP)) channel activity, resulting in reduced insulin secretion and impaired glucose tolerance. No previous studies have investigated the effects of intravenous anesthetics, such as propofol, on pancreatic K(ATP) channels. We investigated the cellular mechanisms underlying the effects of isoflurane and propofol on pancreatic K(ATP) channels and insulin secretion.


Effects of aging on isoflurane-induced and protein kinase A-mediated activation of ATP-sensitive potassium channels in cultured rat aortic vascular smooth muscle cells.

Isoflurane activates protein kinase A (PKA) in vascular smooth muscle cells (VSMCs), which in turn activates ATP-sensitive potassium (K(ATP)) channels and causes vasodilation. The present study was undertaken to examine whether advanced age influences the effect of isoflurane on K(ATP) channel activity in cultured VSMCs. We used VSMCs obtained from 12- to 15-week-old (adult) and 24- to 25-month-old (aged) male Wistar rats. Electrophysiological experiments were performed using cell-attached and inside-out patch-clamp techniques to monitor the K(ATP) channel activity. Application of isoflurane or forskolin to the bath solution in cell-attached recordings induced a significant increase in K(ATP) channel activity in the VSMCs from the adult group. However, K(ATP) channel opening induced by isoflurane, but not forskolin, was significantly suppressed by aging. On the other hand, cell-free recordings showed similar pharmacologic sensitivity to the K(ATP) channel opener pinacidil, inward rectification, and unitary conductance (40 45 pS) between groups. In addition, direct K(ATP) channel activation by c-PKA in the inside-out patches was similar in both groups. Furthermore, increasing PKA activation in cell-attached patches by CPT-cAMP restored isoflurane's effects in the aged group. These results suggest that aging decreases isoflurane-induced PKA activation, resulting in attenuation of K(ATP) channel opening.


小児感染性心内膜炎の周術期管理における心エコーの役割

小児感染性心内膜炎の周術期管理における心エコーの役割

The Japanese Journal of Pediatric Dentistry


Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle.

Nicorandil opens adenosine triphosphate-sensitive potassium (K(ATP)) channels in the cardiovascular system and is being increasingly used for the treatment of angina pectoris. In the present study, we tested whether intravenous anesthetic agent ketamine affected nicorandil-induced native vascular K(ATP) channel activation.


[Assessment of disposable crystal laryngoscope blade].

クリスタル咽頭鏡ブレードの使用経験

We evaluated Disposable Crystal Laryngoscope Blades in terms of preventing infection. Most anesthesiologists were satisfied with the view offered by the Disposable Crystal Laryngoscope Blade; however more force is necessary to lift the epiglottis during intubation. It may be more difficult to use by residents, inexperienced anesthesiologist, or emergency medical technicians, although the Disposable Crystal Laryngoscope blade is useful for preventing infection.


[Anesthetic management of a child with Angelman's syndrome].

Angelman症候群の麻酔経験

Angelman syndrome is a hereditary disease described by Angelman. The clinical features of Angelman syndrome are characterized by mental retardation, puppet-like ataxia, easily excitable personality, seizures, paroxysmal laughter, strabismus and macroglossia. A 4-year-old girl with Angelman syndrome underwent strabismus repair under general anesthesia. Anesthesia was slowly induced with sevoflurane in oxygen and maintained with air, oxygen, propofol and remifentanil. Tracheal intubation was performed after administration of rocuronium. During and after anesthesia, no adverse events regarding circulatory and respiratory systems occurred. However, this case demonstrates that it is necessary to pay attention to airway troubles including the difficulty of tracheal intubation, management of body temperature and chronotropic action or respiratory depression by anesthetic agents.


Autologous Peripheral Blood Mononuclear Cell Implantation for Therapeutic Angiogenesis in a Patient with Buerger's Disease

バージャー病に対する自己末梢血単核球細胞移植による血管新生治療

The Journal of Japan Society for Clinical Anesthesia


L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive ozygen species in rat aorta

To clarify the underlying mechanisms of L-DOPA induced vasoconstriction in rat aorta. Methods: The effect of L-DOPA on phenylephrine-induced contractile force of blood vessels was examined in vitro using rat aortic ring preparations by isometric tension experiment. Involvement of nitric oxide (NO) in the effect of L-DOPA on vascular smooth muscle was studied by using N(omega)-Nitro-L-arginine (L-NNA), Sodium nitroprusside (SNP) in endothelium-intact and endothelium-denuded aortic rings. L-DOPA potentiated alpha-adrenergic receptor- and depolarization-induced vascular contraction and inhibited acetylcholine-induced vasorelaxation. This effect was diminished by pretreatment of the aortic rings with L-NNA, an inhibitor of NO synthesis, or by removing the endothelium from the ring preparations. In endothelium-denuded rings, L-DOPA inhibited exogenous NO-dependent but not cGMP-mediated vasorelaxation. Increases in cGMP levels in response to an NO donor were attenuated by L-DOPA in cultured rat aortic smooth muscle cells. L-DOPA could not contract rings (without endothelium) pretreated with 3-(5'-hydroxymethyl- 2'-furyl)-1-benzyl indazole (YC-1), an activator of guanylyl cyclase, but SOD (150 U/ml) pretreatment of rings with endothelium inhibited contraction by L-DOPA. These results suggest that L-DOPA inhibits nitric-dependent vasorelaxation on vascular smooth muscle cells via production of reactive oxygen species.

The Journal of Medical Investigation : JMI


Anesthetic management for repair of ebstein's anomaly with WPW syndrome

WPW症候群を合併したエプスタイン奇形の麻酔管理

Ebstein's anomaly is a rare congenital malformation of the tricuspid valve, often associated with Wolff-Parkinson-White (WPW) syndrome. We report the perioperative management of 3 patients (a 34-year-old man, a 5-month-old boy and a 5-year-old girl) with Ebstein's anomaly associated with WPW syndrome. Anesthetic managements for valvuloplasty of the tricuspid valve and ablation of accessory pathway in 3 patients were successfully accomplished with a combination of fentanyl, sevoflurane, and midazolam. The management of Ebstein's anomaly is based on its severity. The major concerns with anesthesia for children with Ebstein's anomaly include decreased cardiac output, right-to-left atrial level shunting with cyanosis, and the propensity for atrial tachyarrhythmias. We conclude that perioperative management of arrhythmia and evaluation of residual tricuspid regurgitation using transesophageal echocardiography are essential.


② 意外に難しいスライディング・スケール法による血糖管理 --- 人工膵臓を用いた外科手術周術期血糖管理法


小児先天性心疾患の最終診断のための経食道心エコー

小児先天性心疾患の最終診断のための経食道心エコー


Low-dose sevoflurane inhalation enhances late cardioprotection from the anti-ulcer drug geranylgeranylacetone.

We investigated in rabbits whether sevoflurane enhances late cardioprotection induced by geranylgeranylacetone (GGA), a gastric antiulcer drug. S(+)-ketamine and xylazine-anesthetized rabbits were assigned to one of seven experimental groups: a control (vehicle only) group, a GGA group, a sevoflurane group, a GGA+sevoflurane group, a sodium 5-hydroxydecanoate (5HD) group, a GGA + 5HD group, and a heat stress group. All rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were pretreated with IV vehicle, GGA (10 mg/kg), or heat stress (42 degrees C for 15 min) 24 h before coronary occlusion. Sevoflurane (0.5 minimum alveolar concentration) or 5HD (5 mg/kg) were administered before myocardial ischemia. Myocardial infarct size and the area at risk for ischemia were measured, and heat shock protein (Hsp) 70 levels in each experimental group were determined. Compared with vehicle only, GGA significantly reduced the size of myocardial infarction in relation to the area at risk (39 +/- 10% vs 59 +/- 9%, P < 0.02). Sevoflurane enhanced the GGA-induced cardioprotection (23 +/- 17%, P < 0.05 vs GGA). The cardioprotective effect of GGA was abolished by administration of 5HD (56 +/- 15%, P < 0.01). GGA enhanced Hsp 70 expression compared with that in the control group (0.69 +/- 0.15 vs 0.36 +/- 0.05, P < 0.02). Administration of GGA with sevoflurane resulted in the same level of Hsp 70 expression as GGA (0.69 +/- 0.16, P > 0.98). GGA appears to reduce myocardial infarct size in association with increased Hsp 70 expression. Sevoflurane enhances the GGA-induced cardioprotective effect.


Hyperglycemia impairs isoflurane-induced adenosine triphosphate-sensitive potassium channel activation in vascular smooth muscle cells

Isoflurane activates vascular adenosine triphosphate sensitive potassium (K(ATP)) channels, and may induce vasodilation. In the present study, we investigated whether hyperglycemia modifies isoflurane activation of vascular K(ATP) channel. We used a cell-attached patch-clamp configuration to test the effects of isoflurane on K(ATP) channel activity in vascular smooth muscle cells (VSMCs) after incubation for 24 h in medium containing normal glucose (NG, 5.5 mM D-glucose), L-glucose (LG, 5.5 mM D-glucose plus 17.5 mM L-glucose), or high glucose (HG, 23 mM D-glucose). Superoxide levels in aortas were measured by the lucigenin-enhanced chemiluminescence technique. Isoflurane-induced open probabilities were significantly reduced in VSMCs from arteries incubated in HG (0.06 +/- 0.01) compared with NG (0.17 +/- 0.02; P < 0.05) and LG (0.15 +/- 0.02; P < 0.05). Pretreatment of VSMCs with protein kinase C (PKC) inhibitors, calphostin C and PKC inhibitor 20-28, greatly reduced HG inhibition of isoflurane-induced K(ATP) channel activity. In addition, a PKC activator, PMA, mimicked the effects of HG. Superoxide release was significantly increased in arteries incubated in HG (18.3 +/- 11.5 relative light units (RLU) x s(-1) x mg(-1); P < 0.05 versus NG). Coincubated with polyethylene glycol-superoxide dismutase (250 U/mL), a cell-permeable superoxide scavenger, greatly reduced the HG-induced increase of superoxide, but failed to reduce HG inhibition of isoflurane-induced K(ATP) channel activity. Our results suggest that the metabolic stress of hyperglycemia can impair isoflurane-induced vascular K(ATP) channel activity mediated by excessive activation of PKC. This could impede the coronary vasodilation response to isoflurane, causing ischemia or hypoxia in patients with perioperative hyperglycemia.


Two unusual complications associated with cardiopulmonary bypass for pediatric cardiac surgery detected by transesophageal echocardiography after decannulation.

We describe two rare cases of complications associated with cannulation for cardiopulmonary bypass during pediatric cardiac surgery detected by transesophageal echocardiography (TEE). The first patient (a 20-month-old boy, 11 kg) was scheduled for complete repair of an atrial septal defect and partial anomalous pulmonary venous connection. After decannulation of the superior vena cava, a mosaic jet was observed by means of TEE. The second patient (an 11-month-old boy, 6.4 kg), with a double outlet right ventricle, was scheduled for a hemi-Fontan procedure. After decannulation of the ascending aorta, high blood flow velocity of 4 m x s(-1) was detected by TEE. Intraoperative TEE was useful for early detection of complications associated with cardiopulmonary bypass cannulation during pediatric cardiac surgery.


Intraoperative transesophageal ventricular pacing in pediatric patients.

Journal of Cardiothoracic and Vascular Anesthesia


Effects of dopamine on ATP-sensitive potassium channels in porcine coronary artery smooth-muscle cells

Dopamine is reported to be a coronary vasodilator; however, the exact mechanism of dopamine action in the coronary circulation remains unclear. In this study, we hypothesized that dopamine-induced activation of coronary ATP-sensitive potassium (KATP) channels may be associated with coronary vasodilation. We therefore investigated the direct effects of dopamine on coronary KATP-channel activity. We used patch-clamp configurations to investigate the effects of dopamine on coronary KATP-channel activity. Application of dopamine (10 to 10 M) to the bath solution during cell-attached recordings induced a concentration-dependent increase in KATP-channel activity. In contrast, dopamine failed to activate KATP channels in inside-out patches. Dopamine-induced coronary KATP-channel currents in cell-attached patches were inhibited by pretreatment with the selective D1-like antagonist, Sch-23390, but they were not influenced by the selective D2-like antagonist, domperidone, or the beta-adrenergic receptor antagonist, propranolol. The selective D1-like agonist, SKF-38393, and the adenylyl cyclase activator, forskolin, mimicked the dopamine effects on coronary KATP channels. Furthermore, pretreatment with an inhibitor of protein kinase A, Rp-cAMPS, abolished the dopamine-induced KATP-channel activation. This study demonstrates that dopamine activates coronary KATP channels via signal transduction involving the D1-like dopaminergic receptor-protein kinase A-signaling pathway.


Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3-kinase in cultured vascular smooth muscle cells

The effects of insulin on the vasculature are significant because insulin resistance is associated with hypertension. To increase the understanding of the effects of insulin on the vasculature, we analyzed changes in potassium ion transport in cultured vascular smooth muscle cells (VSMCs). Using the potential-sensitive fluorescence dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)], we found that insulin induced membrane hyperpolarization after 2 min in A10 cells. Insulin-induced hyperpolarization was suppressed by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker. Using a cell-attached patch clamp experiment, the K(ATP) channel was activated by insulin in both A10 cells and isolated VSMCs from rat aortas, indicating that insulin causes membrane hyperpolarization via K(ATP) channel activation. These effects were not dependent on intracellular ATP concentration, but wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, significantly suppressed insulin-induced K(ATP) channel activation. In addition, insulin enhanced phosphorylation of insulin receptor, insulin receptor substrate (IRS)-1 and protein kinase B (Akt) after 2 min. These data suggest that K(ATP) channel activation by insulin is mediated by PI3-K. Furthermore, using a nitric oxide synthase (NOS) inhibitor, we found that NOS might play an important role downstream of PI3-K in insulin-induced K(ATP) channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated hypertension.


Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited. METHODS: The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments.Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells. RESULTS: PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 microM). CONCLUSIONS: The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.


The effects of extracellular pH on vasopressin inhibition of ATP-sensitive K+ channels in vascular smooth muscle cells

Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (K(ATP)) channels and may help to restore vascular tone in patients with vasodilatory shock. In the present study, we investigated whether extracellular acidification modifies the inhibition of vascular K(ATP) channels by AVP. We used a cell-attached patch-clamp configuration to investigate the effects of extracellular pH (pH(o)) on AVP-K(ATP) channel interaction in rat aortic smooth muscle cells. Bath application of AVP significantly inhibited extracellular acidification (pH(o) = 6.5)-induced K(ATP) channel activity in a concentration-dependent manner, with an half-maximal inhibitory concentration (IC50) value of 16.8 pM. Furthermore, bath application of AVP significantly inhibited pinacidil-induced K(ATP) channel activity at mild (pH(o) = 7.0) and severe (pH(o) = 6.5) extracellular acidification, with IC50 values of 266.7 and 21.4 pM, respectively, but failed to significantly inhibit at normal pH (pH(o) = 7.4) or under alkalosis (pH(o) = 9.0). Augmentation of AVP inhibition of vascular K(ATP) channels during extracellular acidification was eliminated by pretreatment with OPC-21268, a specific blocker of the V1 receptor, but not by a V2 blocker, OPC-31260. AVP-induced inhibition was also suppressed by pretreatment with a protein kinase C inhibitor, calphostin C. Our results suggest that AVP inhibits extracellular acidification-induced vascular K(ATP) channel activity, and that the inhibitory effects of AVP on vascular K(ATP) channels are enhanced by extracellular acidification via the V1 receptor-protein kinase C cell-signaling pathway. The potent inhibition of vascular K(ATP) channels by AVP under acidic conditions may make it suitable for management of vasodilatory shock.


Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP-sensitive potassium channels by propofol

Propofol inhibits adenosine triphosphate-sensitive potassium (K(ATP)) channels, which may result in the blocking of ischemic preconditioning in the heart. During cardiac ischemia, sarcolemmal K(ATP) channel activity is regulated by the increased levels of cytosolic metabolites, such as adenosine diphosphate (ADP) and protons. However, it remains unclear whether these cytosolic metabolites modulate the inhibitory action of propofol. The aim of this study was to investigate the effects of intracellular MgADP and acidification on K(ATP) channel inhibition by propofol. We used inside-out patch-clamp configurations to investigate the effects of propofol on the activities of recombinant cardiac sarcolemmal K(ATP) channels, which are reassociated by expressed subunits, sulfonylurea receptor (SUR) 2A, and inwardly rectifying potassium channels (Kir6.2). In the absence of MgADP, propofol inhibited the SUR2A/Kir6.2 channel currents in a concentration-dependent manner, and an IC(50) of 78 microM. Increasing the intracellular MgADP concentrations to 0.1 and 0.3 mM markedly attenuated the inhibitory potency of propofol, and shifted the IC(50) to 183 and 265 microM, respectively. Moreover, decreasing the intracellular pH from 7.4 to 6.5 attenuated the inhibitory potency of propofol, and shifted the IC(50) to 277 microM. In addition, propofol-induced inhibition of truncated Kir6.2DeltaC36 currents, which form a functional channel without SUR2A, was not affected by an increase in intracellular MgADP. However, intracellular acidification (pH 6.5) significantly reduced the propofol sensitivity of Kir6.2DeltaC36 channels. Our results demonstrated that the existence of intracellular MgADP and protons attenuated the direct inhibitory potency of propofol on recombinant cardiac sarcolemmal K(ATP) channels, via SUR2A and Kir6.2 subunits, respectively.


Non-cardiac surgery applications of extracorporeal circulation

Although the efficacy of extracorporeal circulation (ECC) is well established for open-heart surgery, application of ECC in other surgical areas has not been given much attention. Advances in the related surgical technique and anesthetic management combined with refinements in the ECC procedure itself have encouraged several institutions to use ECC for complex non-cardiac surgeries. ECC is beginning to be used for circulatory support or tissue oxygenation during surgery on the lung, brain, liver, and kidney as well as in emergency situations. With ECC, difficult and complex surgeries can be performed more safely, and the success rate of certain surgeries has been positively affected. It is important that the surgeon, anesthesiologist, and perfusionist are trained in non-cardiac surgery applications of ECC. Thus, we review here non-cardiac uses that have emerged and summarize the related procedures.

The Journal of Medical Investigation : JMI


Differential Effects of Etomidate and Midazolam on Vascular Adenosine Triphosphate-sensitive Potassium Channels: Isometric Tension and Patch Clamp Studies.

The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity. In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2DeltaC36 channels), and (4) mutant Kir6.2DeltaC36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2DeltaC36-K185Q channels). Etomidate (> or = 10 m), but not midazolam (up to 10 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10 m; maximum inhibitory concentration: 1.22 x 10 m). Etomidate (> or = 3 x 10 m), but not midazolam (up to 10 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10 m and 1.52 x 10 m, respectively. Etomidate (10 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2DeltaC36 channels, and Kir6.2DeltaC36-K185Q channels with equivalent potency. Clinical concentrations of etomidate, but not midazolam, inhibit the KATP channel activity in vascular smooth muscle cells. The inhibition is presumably through its effects on the Kir6.0 subunit, but not on the SUR subunit, with the binding site different from adenosine triphosphate at the amino acid level.


Isoflurane activates sarcolemmal adenosine Triphosphate-sensitive potassium channels in vascular smooth muscle cells: A role of protein kinase A

Recent evidence indicates that vascular adenosine triphosphate-sensitive potassium (K(ATP)) channels in vascular smooth muscle cells are critical in the regulation of vascular tonus under both physiologic and pathophysiologic conditions. Studies of the interaction of volatile anesthetics with vascular K(ATP) channels have been limited. In the current study, the authors investigated the molecular mechanism of isoflurane's action on vascular K(ATP) channels. Electrophysiologic experiments were performed using cell-attached and inside-out patch clamp techniques to monitor native vascular K(ATP) channels, and recombinant K(ATP) channels comprised of inwardly rectifying potassium channel subunits (Kir6.1) and the sulfonylurea receptor (SUR2B). Isometric tension experiments were performed in rat thoracic aortic rings without endothelium. Application of isoflurane (0.5 mM) to the bath solution during cell-attached recordings induced a significant increase in K(ATP) channel activity, which was greatly reduced by pretreatment with a selective inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). In inside-out patches, isoflurane did not activate K(ATP) channels. Isoflurane significantly activated wild-type recombinant SUR2B/Kir6.1 in cell-attached patches. Isoflurane-induced activation of wild-type channels was diminished in the PKA-insensitive mutant SUR2B-T633A/Kir6.1, SUR2B-S1465A/Kir6.1, and SUR2B/Kir6.1-S385A. In addition, the authors demonstrated that isoflurane-induced PKA activation was associated with isoflurane-induced decreases in isometric tension in the rat aorta. These results indicate that isoflurane activates K(ATP) channels via PKA activation. PKA-dependent vasodilation induced by isoflurane also was observed in isometric tension experiments. Analysis of expressed vascular-type K(ATP) channels suggested that PKA-mediated phosphorylation of both Kir6.1 and SUR2B subunits plays a pivotal role in isoflurane-induced vascular K(ATP) channel activation.


Usefulness of intraoperative transesophageal echocardiography in stent graft implantation for thoracic descending aorta

胸部下行大動脈ステントグラフト留置術における術中経食道心エコーの有用性

Stent graft implantation for thoracic descending aorta is a promising alternative to open repair. Transesophageal echocardiography (TEE) is a sensitive imaging modality for aortic disease. We reviewed our experience with TEE in stent graft implantation for thoracic descending aorta. Five patients underwent stent graft implantation for thoracic descending aorta under general anesthesia. Intraoperative angiography and TEE were used to identify the extent of the aneurysm and the placement of the stent. TEE showed stent graft configuration and presence of leakage in all cases. In three cases, additional stent graft placement or bypass was performed. Useful information was obtained by TEE in enhancing the accuracy of stent graft positioning potentially improving outcomes. TEE may facilitate repair by confirming aortic pathology, identifying endograft placement, and assessing the adequacy of aneurysm sack isolation, presence of leakage, as well as dynamic intraoperative cardiac performance.


Bronchospasm during anesthesia in a patient with Pena-Shokeir syndrome

気管支痙攣を繰り返したPena-Shokeir症候群の麻酔管理

A 3-month-old boy with Pena-Shokeir syndrome underwent tracheotomy under general anesthesia. Patients with this syndrome may present anesthetic problems involving difficulties in tracheal intubation, possibilities of malignant hyperthermia, as well as perioperative respiratory complications related to hypoplasia of the lung. General anesthesia was induced and maintained with sevoflurane (2-3%) and nitrous oxide (0-50%) in oxygen (50-100%). The patient developed bronchospasm during tracheotomy. Atropine and epinephrine were administered intravenously and 5% sevoflurane was inhaled. The bronchospasm was improved gradually and surgery was successfully finished. Pena-Shokeir syndrome is an uncommon disease first reported by Pena & Shokeir in 1974 and characterized by congenital multiple arthrogryposis, characteristic facies, camptodactyly and pulmonary hypoplasia. In the perioperative management for a patient with Pena-Shokeir syndrome, special attention should be paid to abnormalities in the upper and lower respiratory systems, especially bronchospasm.


Minute distance obtained from pulmonary venous flow velocity using transesophageal pulsed Doppler echocardiography is related to cardiac output during cardiovascular surgery

We studied the relationship between minute distance calculated from pulmonary venous flow (PVF) velocity tracing and cardiac output (CO) measured with thermodilution method in patients undergoing cardiovascular surgery. In 32 patients undergoing cardiovascular surgery, simultaneous measurements of hemodynamics including CO and transesophageal pulsed Doppler signals of PVF velocity were performed before and after surgical repair. Minute distance was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF. The minute distance after surgical intervention increased from 1121 +/- 347 cm x sec(-1) to 1764 +/- 538 cm x sec(-1) (p < 0.001; mean +/- SD), while CO increased after surgical intervention from 3.5 +/- 0.9 L x min(-1) to 5.3 +/- 1.1 L x min(-1). Simple linear regression analysis showed that minute distance was related with CO before and after surgical intervention (r = 0.81 and r = 0.76, respectively). The changes in minute distance were also related with those in CO (r = 0.80). The present study demonstrated that minute distance obtained from the pulsed Doppler tracings of PVF velocity was related with CO during cardiovascular surgery in adults. These results suggest that the changes in CO could be estimated from minute distance in pulmonary vein.


Involvement of adenosine triphosphate-sensitive potassium channels in the response of membrane potential to hyperosmolality in cultured human aorta endothelial cells.

The membrane potential of endothelial cells is an important determinant of endothelial functions, including regulation of vascular tone. We investigated whether adenosine triphosphate-sensitive potassium (K(ATP)) channels were involved in the response of membrane potential to hyperosmolality in cultured human aorta endothelial cells. The voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. To investigate the effect of mannitol-, sucrose-, and NaCl-induced hyperosmolality on membrane potential, cells were continuously perfused with Earle's balanced salt solution (285 mOsm/kg H(2)O) containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed to 315 and 345 mOsm/kg H(2)O hyperosmotic medium sequentially in the presence and absence of 1 muM glibenclamide, a well-known K(ATP) channel blocker. Hyperosmotic mannitol significantly induced hyperpolarization of the endothelial cells, which was prevented by 1 microM glibenclamide (n = 6). Estimated changes of membrane potential at 315 and 345 mOsm/kg H(2)O were 13 +/- 8 and 21 +/- 8 mV, respectively. Hypertonic sucrose induced similar changes. However, although hypertonic saline also significantly induced hyperpolarization of the endothelial cells (n = 6), the hyperpolarization was not prevented by 1 muM glibenclamide. In conclusion, K(ATP) channels may participate in hyperosmotic mannitol- and sucrose-induced hyperpolarization, but not in hypertonic saline-induced hyperpolarization in cultured human aorta endothelial cells.


Molecular mechanisms underlying ketamine-mediated inhibition of sarcolemmal adenosine triphosphate-sensitive potassium channels.

Ketamine inhibits adenosine triphosphate-sensitive potassium (KATP) channels, which results in the blocking of ischemic preconditioning in the heart and inhibition of vasorelaxation induced by KATP channel openers. In the current study, the authors investigated the molecular mechanisms of ketamine's actions on sarcolemmal KATP channels that are reassociated by expressed subunits, inwardly rectifying potassium channels (Kir6.1 or Kir6.2) and sulfonylurea receptors (SUR1, SUR2A, or SUR2B). The authors used inside-out patch clamp configurations to investigate the effects of ketamine on the activities of reassociated Kir6.0/SUR channels containing wild-type, mutant, or chimeric SURs expressed in COS-7 cells. Ketamine racemate inhibited the activities of the reassociated KATP channels in a SUR subtype-dependent manner: SUR2A/Kir6.2 (IC50 = 83 microM), SUR2B/Kir6.1 (IC50 = 77 microM), SUR2B/Kir6.2 (IC50 = 89 microM), and SUR1/Kir6.2 (IC50 = 1487 microM). S-(+)-ketamine was significantly less potent than ketamine racemate in blocking all types of reassociated KATP channels. The ketamine racemate and S-(+)-ketamine both inhibited channel currents of the truncated isoform of Kir6.2 (Kir6.2DeltaC36) with very low affinity. Application of 100 mum magnesium adenosine diphosphate significantly enhanced the inhibitory potency of ketamine racemate. The last transmembrane domain of SUR2 was essential for the full inhibitory effect of ketamine racemate. These results suggest that ketamine-induced inhibition of sarcolemmal KATP channels is mediated by the SUR subunit. These inhibitory effects of ketamine exhibit specificity for cardiovascular KATP channels, at least some degree of stereoselectivity, and interaction with intracellular magnesium adenosine diphosphate.


Anesthetic management of a patient undergoing cardioverter defibrillator implantation: usefulness of transesophageal echocardiography and near infrared spectroscopy.


Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate-sensitive Potassium Channels in the Cardiovascular System.

Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.


Risk factors for perioperative myocardial ischemia in carotid artery endarterectomy.

To identify variables associated with perioperative myocardial ischemia in patients undergoing carotid artery endarterectomy (CEA). Prospective, observational study. University-affiliated hospital operating room and intensive care unit. One hundred twenty-eight consecutive patients who underwent CEA during a 7-year period. Patients had general anesthesia with sevoflurane or isoflurane. CEA was performed by standard methods with shunting if clinically indicated. Holter electrocardiogram (ECG) monitoring was performed during surgery and 24 hours after surgery. The incidence of perioperative myocardial ischemia was examined, and perioperative risk factors were analyzed. Nineteen patients (15%) showed significant perioperative ECG abnormalities indicative of myocardial ischemia (10 patients during surgery, 12 patients after surgery, and 3 patients both during and after surgery). Multivariate analysis showed perioperative myocardial ischemia to be significantly associated with a history of angina (odds ratio, 11.68; 95% confidence interval, 2.64-51.70) and a history of hypertension (odds ratio, 14.08; 95% confidence interval, 1.51-131.04). The data indicate that perioperative myocardial ischemia defined as an ECG abnormality does not often occur in patients undergoing CEA. However, angina and hypertension may be important risk factors warranting further investigation.

Journal of Cardiothoracic and Vascular Anesthesia


Effect of propofol on hypotonic swelling-induced membrane depolarization in human coronary artery smooth muscle cells.

Stretch (mechanical stress)-induced membrane depolarization of smooth muscle may contribute to basal vascular tone and myogenic control. Propofol induces vasodilation and inhibits myogenic control. Hypotonic swelling was used as a model of mechanical stress. The authors investigated the effects of propofol and 5-nitro-2-(3-phenylpropylamino)benzoic acid, a chloride channel and nonselective cation channel blocker, on hypotonicity-induced membrane depolarization in cultured human coronary artery smooth muscle cells. A voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. The cells were continuously perfused with Earle's balanced salt solution containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed sequentially to isotonic and hypotonic medium. In a second series of experiments, the cells were exposed to hypotonic media in the presence and absence of 5-nitro-2-(3-phenylpropylamino)benzoic acid or propofol. The relative fluorescence values at 10, 20, and 30% hypotonicity were 147 +/- 29, 214 +/- 74, and 335 +/- 102% of baseline, respectively. The changes were all significantly different from the isotonic time control group. In the presence of 200 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or 0.1, 1, 10, or 100 microg/ml propofol, the relative fluorescence values at 30% hypotonicity were 87 +/- 17, 194 +/- 27, 160 +/- 18, 130 +/- 18, and 84 +/- 15%, respectively. These changes were significantly less than the 30% for the hypotonic control (246 +/- 23%). These results suggest that volume-sensitive chloride channels and nonselective cation channels may participate in hypotonicity-induced membrane depolarization and that propofol inhibits hypotonicity-induced membrane depolarization in coronary artery smooth muscle.


Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels.

Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal. These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.


Phenylephrine increases pulmonary blood flow in children with tetralogy of Fallot.

Although it has been reported that the increase in blood pressure improves arterial oxygen saturation (SaO(2)) in children with tetralogy of Fallot, no prospective study has demonstrated that an increase in blood pressure induces an increase in pulmonary blood flow in these patients. The purpose of this study was to see whether a phenylephrine-induced increase in systemic blood pressure increased pulmonary blood flow, resulting in improved arterial oxygenation in tetralogy of Fallot. In 14 consecutive children with tetralogy of Fallot (2-32 months old), transesophageal pulsed Doppler signals of left upper pulmonary venous flow (PVF) velocity were recorded before and four minutes after 10 micro g x kg(-1) of phenylephrine i.v. Simultaneously, arterial blood gas analysis and hemodynamic measurements were performed. The minute distance (MD) was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF. Phenylephrine iv increased mean arterial blood pressure from 54 +/- 8 mmHg to 73 +/- 10 mmHg. This phenylephrine-induced hypertension significantly increased SaO(2) and MD (92.0 +/- 7.5 vs 95.0 +/- 5.0% and 1318 +/- 344 vs 1533 +/- 425 cm x min(-1), respectively). There was a significant correlation (r = 0.72) between the change in MD and the change in SaO(2). Our results suggest that the phenylephrine-induced increase in systemic blood pressure produces an increase in pulmonary blood flow in tetralogy of Fallot. Our results further suggest that this increase in pulmonary blood flow is involved in the mechanism of phenylephrine-induced improvement of arterial oxygenation in tetralogy of Fallot.


Intraoperative transoesophageal echocardiography in a low birth weight neonate with atrioventricular septal defect.

An 18-day-old male neonate (45 cm, 1.8 kg) with a history of cyanosis and congestive heart failure from an atrioventricular septal defect (AVSD) with a large left-to-right shunt was scheduled for surgical repair of the AVSD. After routine induction of anaesthesia with fentanyl and vecuronium, a 4.5-mm diameter transoesophageal echocardiography (TOE) probe was inserted into the oesophagus, and systematic echocardiographic evaluation was performed during surgery. After cardiopulmonary bypass was stopped, intraoperative TOE revealed mild residual mitral valve regurgitation. Because good left ventricular wall motion was confirmed and haemodynamic parameters were stable, cardiopulmonary bypass was not reinitiated. The patient's cardiac output was low in the postoperative intensive care unit. TOE was performed the next day to detect the source of this problem, revealed severe regurgitation compared with that observed intraoperatively. TOE was useful for evaluation of the residual mitral valve regurgitation, and we reconfirmed the importance of continuous monitoring even in a low birthweight neonate undergoing repair of a complete AVSD.


Propofol inhibits volume-sensitive chloride channels in human coronary artery smooth muscle cells.

Volume-sensitive chloride channels (VSCC) play an important role in regulation of cell volume and electrical activity. Activation of vascular smooth muscle VSCC causes smooth muscle depolarization and contraction. We investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells by using the chloride-sensitive dye 6-methoxy-N-ethylquinolinium (MEQ). To activate VSCC, cells were superfused for 2 min with hypotonic gluconate solutions and then potassium thiocyanate solution. The percentage reduction in MEQ fluorescence during 60 s in the presence of potassium thiocyanate was measured and used as an index of VSCC activity. 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a well characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. The reduction in fluorescence was inversely related to osmolality, indicating that activation of VSCC is osmolality dependent. Hypotonic gluconate solution (210 mOsm/kg H(2)O) reduced fluorescence by 38.9% +/- 2.6% of the baseline value. The reduction in fluorescence was dose-dependently inhibited by NPPB. Propofol at 0.3, 1, 3, 10, 30, and 100 micro g/mL significantly inhibited the reduction in fluorescence to 23.6% +/- 4.8%, 19.7% +/- 7.4%, 18.2% +/- 3.5%, 17.6% +/- 5.0%, 15.8% +/- 3.1%, and 10.3% +/- 3.9% of the baseline value, respectively. Our results indicate that propofol inhibits VSCC in a dose-dependent manner in human coronary artery smooth muscle cells.


Dynamic QRS-complex and ST-segment monitoring by continuous vectorcardiography during carotid endarterectomy.

Many authors report a high incidence of cardiac events during carotid endarterectomy. The aim of the present study was to evaluate the usefulness of dynamic continuous on-line vectorcardiography for monitoring the occurrence of myocardial ischaemia during carotid endarterectomy. We studied 21 patients undergoing carotid endarterectomy. Patients underwent general anaesthesia with isoflurane or sevoflurane. The vectorcardiogram was monitored continuously during carotid endarterectomy. Electrodes were placed according to the previously described lead system and connected to a computerized system for on-line vectorcardiography. Two trend variables were recorded: the QRS vector difference, which reflects changes in the shape of the QRS complex; and the ST vector magnitude, which represents deflection of the ST segment from the isoelectric level. The ST segment deflection was measured 60 ms after termination of the QRS complex. Vectorcardiography was successfully recorded in all 21 patients. Three patients showed intraoperative vectorcardiogram abnormalities. In one of these three patients, both ST vector magnitude and QRS vector difference increased after induction of anaesthesia and ST vector magnitude returned to baseline after administration of nitroglycerin. In the other two patients, both ST vector magnitude and QRS vector difference gradually increased after cross-clamping of the internal carotid artery and ST vector magnitude returned to baseline after unclamping. QRS vector difference remained elevated for several hours in all three patients. Monitoring ST vector magnitude and QRS vector difference by vectorcardiography may be useful for identifying myocardial ischaemia during carotid endarterectomy.


Effects of acute normovolemic hemodilution on ventriculoarterial coupling in dogs.

Acute normovolemic hemodilution (ANH) causes a decrease in systemic vascular resistance. Similar to vasodilating drugs, ANH might modify ventriculoarterial coupling. Left ventricular elastance (Ees), effective arterial elastance (Ea), stroke work (SW), and pressure volume area (PVA) were used as indicators to examine the effects of ANH on this coupling. After institutional approval eight dogs were anesthetized with isoflurane and subjected to measurements including aortic pressure, left ventricular (LV) pressure, and LV volume. Left ventricular volume was measured with a conductance catheter. Ees was determined as the slope of the end-systolic pressure-volume relationship. Ea was determined as the ratio of LV end-systolic pressure to stroke volume. Ventriculoarterial coupling was evaluated as the ratio of Ees to Ea. Mechanical efficiency, another criterion for ventriculoarterial coupling, was calculated as the ratio of SW to PVA. Data are expressed as mean+/-SD, and P<0.05 was considered significant. Normovolemic exchange of 50 ml kg-1 of blood for 6% hydroxyethyl starch (ANH50) reduced hemoglobin concentration from 12.8+/-3.0 g dl-1 to 6.4+/-1.3 g dl-1. Acute normovolemic hemodilution 50 did not change Ees significantly although it significantly decreased Ea. Left ventricular elastance/Ea did not change after ANH (1.0+/-0.4 at baseline and 1.2+/-0.5 at ANH50). Acute normovolemic hemodilution 50 significantly increased SW and PVA, preventing SW/PVA from changing significantly after ANH (0.57+/-0.10 at baseline and 0.62+/-0.14 at ANH50). Before ANH, ventriculoarterial coupling was so matched as to maximize SW at the expense of the work efficiency. This relation was preserved at ANH50.


Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes.

Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia. The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels. In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml. Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).


The effects of acute normovolemic hemodilution on left ventricular systolic and diastolic function in the absence or presence of beta-adrenergic blockade in dogs.

Acute normovolemic hemodilution (ANH) increases cardiac output because of a reduction in blood viscosity and enhancement of left ventricular (LV) contractility. The status of LV function, especially LV diastolic function during ANH, remains controversial. We therefore examined LV systolic and diastolic function during ANH. Sixteen dogs were anesthetized with isoflurane in the absence (Group 1) and presence (Group 2) of beta-adrenergic blockade (propranolol 1 mg/kg). LV contractility was quantified by the slope (M(w)) of the stroke work and end-diastolic volume relation. Diastolic function was evaluated with the time constant of LV relaxation (T), chamber stiffness constant (K(c)), peak LV diastolic filling rate during early filling (peak E) and atrial contraction (peak A), and ratio of peak E to peak A (E/A). Normovolemic exchange of blood (50 mL/kg) for 6% hydroxyethyl starch (ANH50) significantly increased M(w) in Group 1 but not in Group 2. In both groups, ANH50 significantly decreased T. ANH50 significantly increased peak E in both groups and peak A in Group 1, and it did not change the E/A ratio or K(c) in either group. ANH causes positive inotropic effects and enhances diastolic function without beta-blockade. Even after beta-adrenergic blockade, ANH improves diastolic function through the reduction of LV ejection impedance. IMPLICATIONS: Acute normovolemic hemodilution enhances LV (left ventricular) diastolic function by alterations in the LV loading condition produced by hemodilution, which mainly contributes to a compensatory increase in cardiac output.


人工呼吸器の保守管理におけるIT化

人工呼吸器の保守管理におけるIT化


Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes.

Accumulating evidence suggests that mitochondrial rather than sarcolemmal adenosine triphosphate-sensitive K+ (K(ATP)) channels may have an important role in the protection of myocardium during ischemia. Because both lidocaine and mexiletine are frequently used antiarrhythmic drugs during myocardial ischemia, it is important to investigate whether they affect mitochondrial K(ATP) channel activities. Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. The authors measured flavoprotein fluorescence to evaluate mitochondrial redox state. Lidocaine or mexiletine was applied after administration of diazoxide (25 microM), a selective mitochondrial K(ATP) channel opener. The redox signal was normalized to the baseline flavoprotein fluorescence obtained during exposure to 2,4-dinitrophenol, a protonophore that uncouples respiration from ATP synthesis and collapses the mitochondrial potential. Diazoxide-induced oxidation of flavoproteins and the redox changes were inhibited by 5-hydroxydecanoic acid, a selective mitochondrial K(ATP) channel blocker, suggesting that flavoprotein fluorescence can be used as an index of mitochondrial oxidation mediated by mitochondrial K(ATP) channels. Lidocaine (10(-3) to 10 mM) and mexiletine (10(-3) to 10 mM) reduced oxidation of the mitochondrial matrix in a dose-dependent manner with an EC50 of 98+/-63 microM for lidocaine and 107+/-89 microM for mexiletine. Both lidocaine and mexiletine reduced flavoprotein fluorescence induced by diazoxide in rat ventricular myocytes, indicating that these antiarrhythmic drugs may produce impairment of mitochondrial oxidation mediated by mitochondrial K(ATP) channels.


Pulmonary arterial pressure can be estimated by transesophageal pulsed Doppler echocardiography.

We examined whether pulmonary arterial pressure can be estimated on the basis of pulmonary arterial flow velocity determined via intraoperative pulsed Doppler transesophageal echocardiography (TEE) in 20 patients undergoing cardiac surgery. Standard pulmonary artery measurements were taken as well. Measurements were taken before sternotomy, after pericardiotomy, after cardiopulmonary bypass, and after sternum closure. The variables obtained by TEE included preejection period (PEP), acceleration time (AT), right ventricular ejection time (RVET), and R-R interval (RR). Five ratios were calculated as indices of pulmonary arterial pressure--PEP/AT, PEP/RVET, AT/RVET, PEP/ square root of RR, and AT/ square root of RR--and were compared with pulmonary artery catheterization findings, i.e., systolic pulmonary arterial pressure (sPAP), log sPAP, mean PAP (mPAP), and log mPAP. Before sternotomy, PEP/AT, PEP/ square root of RR, and AT/ square root of RR showed significant correlation with all pulmonary artery catheterization values. AT/RVET showed correlation with all pulmonary artery values except log mPAP. PEP/AT showed the closest correlation with sPAP (r = 0.771) and log sPAP (r = 0.789). PEP/AT also showed close correlation with mPAP (r = 0.764) and log mPAP (r = 0.777). Significant agreement between sPAP and mPAP values calculated from a regression equation and values measured via pulmonary artery catheter was observed by plotting the differences against the mean values of the two measurements. We therefore conclude that noninvasive estimation of pulmonary arterial pressure is feasible via intraoperative TEE when sternotomy is not involved.


Bronchospasm induced by cardiopulmonary bypass.

Annals of Thoracic and Cardiovascular Surgery


Intraoperative evaluation of pulmonary artery flow during the Fontan procedure by transesophageal Doppler echocardiography.

After the Fontan procedure, pulmonary artery (PA) flow is maintained without right ventricular pump function. We evaluated intraoperative PA flow velocity patterns using transesophageal Doppler echocardiography (TEE) immediately after cardiopulmonary bypass (CPB) in patients during Fontan or hemi-Fontan procedures. We studied 10 patients with single-ventricle physiology (age range, 5 mo to 3 yr 1 mo). Anesthesia was induced and maintained with fentanyl. After induction of anesthesia, a pediatric TEE probe was inserted into the esophagus. All patients had surgical repair involving direct anastomosis of the right atrium to the PA. Immediately after completion of CPB, adequacy of the atriopulmonary anastomosis was assessed and PA flow velocity was recorded. In all patients, the atriopulmonary anastomosis was clearly defined using a single-plane TEE probe, and PA flow recording was completed successfully. Intraoperative PA flow velocities showed two distinct patterns. Biphasic forward flows with peak velocities during systole and diastole were observed in six patients. The remaining four patients showed forward flows with flow reversals. The four patients demonstrating flow reversals showed significantly reduced fractional shortening (26.5+/-2.1% vs. 35.5+/-6.3%) and larger pressure gradient between the right atrium and left atrium (10.8+/-1.3 mm Hg vs 8.0+/-0.9 mm Hg) when compared to those without reverse flow. Two patients with reverse flow required reoperation because of hypotension. Because PA flow is influenced by pulmonary vascular resistance and left ventricular function, TEE assessed intraoperative PA flow should be further evaluated as a useful predictor of surgical outcome after a Fontan procedure.


Transesophageal echocardiography for intraoperative management of the fenestrated Fontan procedure.

Journal of Cardiothoracic and Vascular Anesthesia


Transesophageal echocardiographic assessment of pulmonary arterial and venous flow during high-frequency jet ventilation.

To evaluate high-frequency jet ventilation (HFJV) effects on pulmonary arterial and venous flow compared to those of intermittent positive-pressure ventilation (IPPV) by using pulsed Doppler transesophageal echocardiography. Prospective clinical study. University-affiliated hospital operating room.Patients: 13 ASA physical status I and II patients undergoing lower abdominal or lower extremity surgery. Patients had total IV anesthesia with propofol and fentanyl. After anesthesia induction, a transesophageal echocardiography probe was inserted into the esophagus. IPPV (TV, 8-10 mL/kg; respiratory rate, 10-12 cycles/min; I/E ratio, 1:2; FIO(2), 1.0) and HFJV (driving pressure, 0.5-0.6 kgf/cm(2); frequency,3 Hz; I/E ratio, 1:1; FIO(2), 1.0) were performed under hemodynamically stable conditions. Pulmonary-arterial-flow velocity, pulmonary-venous-flow velocity, left ventricular short-axis view, and airway-pressure curve were recorded simultaneously. Parameters measured were: hemodynamic variables, arterial blood gases, inspiratory airway pressure; [from pulmonary-arterial-flow velocity] pre-ejection period (PEP), acceleration time (AT), right ventricular ejection time (RVET), and their ratios (PEP/AT, AT/RVET); [from pulmonary-venous-flow velocity] time-velocity integral of the first systolic wave (S1), second systolic wave (S2), and diastolic wave (D), and systolic fraction (integral S1 + S2/S1+ S2 + D); [from M-mode] left-ventricular-end systolic volume, left-ventricular-end diastolic volume (LVEDV), stroke volume, cardiac output, and ejection fraction, using Teichholz's method. Peak inspiratory airway pressure during HFJV was significantly lower than that during IPPV. HFJV significantly decreased PEP/AT, correlating positively with pulmonary arterial pressure, and significantly increased AT and AT/RVET, correlating negatively with pulmonary arterial pressure. Systolic fraction, correlating negatively with left atrial pressure, increased significantly during HFJV, as did LVEDV, stroke volume, cardiac output, and ejection fraction. Our results suggest that, in comparison to IPPV, HFJV significantly decreases pulmonary arterial pressure and left atrial pressure, resulting in significant increases in cardiac output and ejection fraction in healthy anesthetized adults.


Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes.

The adenosine triphosphate (ATP)-sensitive potassium (KATP) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATP channels in isolated rat ventricular myocytes during simulated ischemia. Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of thiamylal (50 mg/1). In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KATP channels. Open probability of KATP channels was reduced by thiamylal in a concentration-dependent manner. KATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited KATP channel activity without changing the single-channel conductance. The results obtained in this study indicate that thiamylal inhibits KATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.


Nitric oxide does not play a major role in the regulation of systemic hemodynamic responses to acute normovolemic hemodilution.

The mechanisms of cardiovascular changes following acute normovolemic hemodilution (ANH) have not been fully elucidated. We tested the hypothesis that inhibition of nitric oxide synthesis attenuates ANH-induced cardiovascular responses. We observed the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) pretreatment on ANH-induced cardiovascular responses and compared these effects with those elicited by phenylephrine (PHE). Twenty dogs anesthetized with isoflurane were divided into two groups: one group was pretreated with L-NAME and the other with PHE. Both groups were normovolemically hemodiluted using 6% hydroxyethyl starch to reduce the hemoglobin concentration to approximately 50% of the pretreatment value. Pretreatment with either L-NAME or PHE caused a significant increase in mean aortic blood pressure (MAP) and systemic vascular resistance (SVR) with a significant decrease in cardiac output (CO) and stroke volume (SV). However, no remarkable differences in these variables were seen between groups. In both groups ANH produced increases in heart rate, CO, SV, and maximal left ventricular dP/dt with a significant decrease in SVR. No significant differences in these variables were apparent after ANH except that MAP was decreased in the PHE group but not in the L-NAME group. Our results suggest that nitric oxide does not play a major role in mediation or modulation of the systemic vascular responses to ANH.


Effect of endothelin-1 (1-31) on intracellular free calcium in cultured human mesangial cells.


Recurrent laryngeal nerve palsy after cardiovascular surgery --- Relationship to the placement of a transesophageal echocardiographic probe

To examine the relationship between the incidence of recurrent laryngeal nerve palsy after cardiovascular surgery and the placement of a transesophageal echocardiographic probe. A prospective clinical study. A single-institutional study in a university hospital. One hundred sixteen patients undergoing cardiovascular surgery. All patients were assigned into one of two groups: 64 patients in whom transesophageal echocardiography (TEE) was performed and 52 patients in whom TEE was not performed during surgery. The incidence of recurrent laryngeal nerve palsy was examined and compared between the two groups. Five of 64 patients (7.8%) in whom TEE was monitored and 3 of 52 patients (5.8%) in whom TEE was not monitored were diagnosed with recurrent laryngeal nerve palsy postoperatively. There was no statistically significant difference between the incidence of recurrent laryngeal nerve palsy in patients with intraoperative TEE monitoring, and patients without it. The durations of surgery, anesthesia, and cardiopulmonary bypass were significantly longer in patients with nerve palsy than those without it. These results suggest that placement of the transesophageal echocardiographic probe is not responsible for postoperative recurrent laryngeal nerve palsy. It seems likely that surgical manipulation itself and the durations of surgery, cardiopulmonary bypass, and tracheal intubation are related to the incidence of laryngeal nerve palsy.


Autotransfusion performed on a patient with cis AB blood group.

Cis AB blood group is a rare variant of the AB blood group resulting from inheritance of both A and B genes on one chromosome. It may lead to misclassification in ABO grouping and clinical misdiagnosis as a result of its divergence from the laws of Landsteiner and Mendel. We encountered a case of cis AB blood group, and we found that autotransfusion was useful during surgery in this patient with a rare blood group.


Pulmonary hemodynamics --- Intraoperative assessment with transesophageal Doppler echocardiography


The feasibility of gastrothoracic ventricular pacing during transesophageal echocardiography.

We evaluated whether ventricular pacing is possible using pacing electrodes attached to a transesophageal echocardiography (TEE) probe in 20 patients undergoing elective cardiovascular surgery. A bipolar pacing lead was fixed with silicone adhesive anteriorly to the TEE probe with the distal electrode 25 mm from the TEE probe tip. The TEE probe was positioned to obtain a transgastric short-axis view of the left ventricle. The distal or proximal electrode on the TEE probe was the cathode; the chest electrode placed at the V5 lead position was the anode. Gastrothoracic ventricular pacing (GVP) was performed at 100 bpm at 30- or 50-ms pulse duration. Transgastric ventricular pacing (TVP) was also attempted using both TEE probe electrodes alternately as cathode/anode. Maximal generator output was 32 mA. GVP with the distal electrode as cathode was successful in 75% and 80% of patients at 30- and 50-ms pulse durations and 23.3+/-5.8 mA and 22.6+/-5.8 mA threshold currents, respectively. However, success rates (20% and 25%, respectively) were significantly lower with the proximal electrode as cathode using the same pulse durations and 14.4+/-5.3 mA and 16.7+/-6.8 mA threshold currents. The TVP success rate was significantly lower than that for GVP. With optimization, this system could become an available technique for intraoperative emergency ventricular pacing. Using an endocardial pacing lead attached to a transesophageal echocardiography probe, gastrothoracic ventricular pacing can be performed successfully without complications in 75%-80% of patients undergoing cardiovascular surgery.


Intraoperative management of a pediatric patient undergoing cardiac tumor resection with the aid of transesophageal and epicardial echocardiography.


effects of sevoflurane on regional myocardial blood flow distribution --- Quantification with myocardial contrast echocardiography

Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs. In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level corrected for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration). In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery. These results suggest that dipyridamole, a potent coronary vasodilator, produces maldistribution of coronary blood flow in our dog models, whereas sevoflurane does not do this in animal or human studies.


Simultaneous transesophageal echocardiography and atrial pacing for intraoperative management of mitral regurgitation.


Anaesthetic management of a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.

A case of a patient associated with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis is presented. Williams syndrome is a rare disease associated with a characteristic facies, supravalvular aortic stenosis, and mental retardation. A 15-yr-old girl with Williams syndrome underwent aortoplasty for supravalvular aortic stenosis. Anaesthesia was induced with fentanyl and thiamylal, and maintained with nitrous oxide, oxygen, sevoflurane, and continuous intravenous infusion of fentanyl. Supravalvular aortic stenosis was evaluated using a multiplane transesophageal echocardiography (TEE) probe before and after repair. Multiplane TEE was found to be very useful for anaesthetic management in a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.


Effects of nicardipine on ventriculo-arterial coupling in humans.

The ratio of effective arterial elastance (Ea) to left ventricular elastance (Ees) is an indicator of the coupling between ventricular properties and arterial load properties. Another criterion for the coupling between an energy source and its load is the principle of economical fuel consumption, or mechanical efficiency, which is defined as the ratio of stroke work (SW) to myocardial oxygen consumption per beat (MVO2). It has been revealed that SW of ventricular contraction is maximized when Ea/Ees = 1, while mechanical efficiency is maximized when Ea/Ees = 0.5. The purpose of the present study was to investigate the ventriculo-arterial coupling during hypertension, and the effects of nicardipine on this relationship in surgical patients using Ea/Ees and SW/MVO2 as indicators. Anaesthesia was maintained with isoflurane, nitrous oxide, and fentanyl. Radial artery pressure was displayed on a polygraph, and left ventricular end-systolic and end-diastolic volumes were determined by use of transoesophageal echocardiography. Ees was calculated as MAP/(ESVI-4), where MAP is mean arterial pressure and ESVI is end-systolic volume index. Ea was calculated as the ratio of MAP to stroke volume index (SVI). Stroke work index (SWI) was calculated as the product of MAP and SVI. MVO2 was assessed by estimating the ventricular pressure-volume area index (PVAI), which is expressed as the sum of SWI and the end-systolic potential energy index. Before (baseline), and 3, 10, 20, and 30 min after i.v. nicardipine (30 micrograms kg-1), Ea/Ees and SWI/PVAI were determined in 14 surgical patients with intraoperative hypertension. Before nicardipine (during hypertension), Ea was almost equal to Ees, whereas Ea/Ees was significantly reduced to about 0.5-0.6 at 3, 10, and 20 min after nicardipine. SWI/PVAI was maximized and significantly greater than the baseline value at 3 min after nicardipine. These results suggest that, during hypertension, ventricular and arterial properties were so matched as to maximize SW at the expense of the work efficiency, whereas mechanical efficiency of ventricular contraction was maximized after nicardipine.


Role of left atrial appendage in left atrial reservoir function as evaluated by left atrial appendage clamping during cardiac surgery.


Transdiscal lumbar sympathetic block: a new technique for a chemical sympathectomy

Genitofemoral neuritis, which occurs when the neurolytic solution spreads into the psoas muscle, is the most common complication after neurolytic lumbar sympathetic block. We developed a transdiscal approach for neurolytic lumbar sympathetic block to reduce the danger of genitofemoral neuritis by making a sympathectomy without penetration of the psoas muscle, through which the genitofemoral nerve passes. We attempted transdiscal lumbar sympathetic block in 14 patients for whom the last previous lumbar sympathetic block performed by using the conventional paravertebral method was unsuccessful. Under fluoroscopic guidance, the needle was inserted transdiscally at L2-3 and/or L3-4 and was advanced until its tip pierced the anterior longitudinal ligament. Radiography and computed tomography revealed that the injected contrast media spread along the anterolateral surface of the vertebral column without any flow into the psoas muscle. Alcohol was injected successfully in all patients. During the 1-mo follow-up period, no patients had any symptom of genitofemoral neuritis. Thirteen patients who had been suffering from lower extremity pain achieved partial or complete pain relief. One patient with plantar hyperhidrosis achieved persistent anhidrosis. These results suggest that the transdiscal approach can be a technical option for neurolytic lumbar sympathetic block. Neurolytic lumbar sympathetic block was performed with the needle advanced through the intervertebral disc. With this technique, the risk of genitofemoral neuritis, the most common complication after neurolytic lumbar sympathetic block, was reduced because the needle does not penetrate the psoas muscle, through which the genitofemoral nerve passes.


Comparative effects of acetate and bicarbonate dialysates on the hemodynamic and respirstory states during continuous hemodiafiltration in critically ill patients

The bulletin of the Yamaguchi Medical School


The determination of nitrite and nitrate in human blood olasma by capillary zone electrophoresis


Astudy of desensitization of rat muscle nicotinic acetylcholine receptor ezpressed in Xenops oocytes as affected by vecuronium and lidocaine


Hypertension control during anesthesia. Fuzzy logic regulation of nicardipine infusion

IEEE Engineering in Medicine and Biology Magazine


Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria


Enflurane increases the adrenaline threshold for the development of slow responses in isolated canine trabeculae

To determine if enflurane has different effects on myocardial sensitivity to adrenaline than those previously reported for halothane, we have studied the enflurane-adrenaline interaction in isolated canine trabeculae using doses of adrenaline necessary to produce slow responses (adrenaline threshold for the development of slow responses, ATSR) as an indicator. The preparations were depolarized in Tyrode's solution containing potassium chloride 26 mmol litre-1, then adrenaline concentrations in the solution were increased stepwise. Enflurane 1% had no significant effect, but 2% and 4% significantly increased the ATSR two-fold and seven-fold, respectively. To investigate the influence of enflurane on the adrenaline-adrenoceptor interaction, we studied the effects on the ATSR of 2% enflurane alone or in combination with either prazosin 8 ng ml-1 or metoprolol 17 ng ml-1. Compared with the ATSR obtained with 2% enflurane alone, alpha 1-block with prazosin did not alter, but beta 1-block with metoprolol significantly increased the ATSR (three-fold). These effects on enflurane are qualitatively as well as quantitatively similar to those reported previously for halothane. Thus, assuming that the MAC value for enflurane is about 2-2.5 times greater than that for halothane, the effects of enflurane on slow channel conductance (antiarrhythmic effects of enflurane) might be about two to three times greater than those of halothane at equivalent depth of anaesthesia. Such differences may explain in part the clinical observation that ventricular arrhythmias are less likely with enflurane than with halothane.


Central nervous system complications after cardiac surgery: a comparison between coronary artery bypass grafting and valve surgery


Cerebral blood flow and cerebral oxygen consumption in patients with COPD on mechanical ventilation


Halothane increases epinephrine threshold for the development of slow responses in isolated canine trabeculae


Pretreatment with d-tubocurarine, vecuronium, and pancuronium attenuates succinylcholine-induced increases in plasma norepinephrine concentrations in humans


The antinociceptive effects of intrathecally administered SCH32615, an enkephalinase inhibitor in the rat


Cerebrovascular reactivity to CO2 in patients with hepatic or septic encephalopathy

The authors studied the effects of hypocapnic-hyperventilation on cerebral blood flow (CBF) (study 1) and on cerebral oxygenation (study 2) during mechanical ventilation in 8 patients, 4 with hepatic (HE) and 4 with septic encephalopathy (SE). In study 1, a positive linear relationship between CBF(y) and PaCO2 (x) was observed (y = 2.44x - 55.5, r = 0.6276, P less than 0.01, n = 18). In the study 2, hypocapnic-hyperventilation produced a reduction in CBF below the level required to meet the demand in 4 of 8 patients. A good linear relationship was observed between CBF/CMRO2 (CMRO2 = cerebral oxygen consumption, y) and jugular venous PO2 (PjVO2, x) (y = 0.99x - 15.53, r = 0.8962, P less than 0.01, n = 18). It is concluded that cerebrovascular reactivity to CO2 was preserved in these patients, therefore, intentional or inadvertant hyperventilation may produce cerebral ischemia. Moreover, JPVO2 may be useful in monitoring cerebral oxygenation in such patients.


Synergetic effects of dopamine and high-dose bumetanide in patients with oliguria


Epidural bupivacaine suppresses local glucose utilization in the spinal cord and brain of rats


Prolonged neuromuscular and cardiovascular effects of succinylcholine in a patient homozygous for the silent gene

The bulletin of the Yamaguchi Medical School


Correlation between arterial blood pressure and oxygenation in Tetralogy of Fallot

Journal of Cardiothoracic and Vascular Anesthesia


Alcuronium pretreatment attenuates succinylcholine-induced increases in plasma catecholamine concentrations in humans


Lidocaine modifies the effect of succinylcholine on muscle oxygen consumption in dogs


A method for measurement of internal longitudinal resistance in papillary muscle

American Journal of Physiology, Heart and Circulatory Physiology


Prolonged neuromuscular blockade following succinylcholine in a patient homozygous for the silent gene


Effects of prenylamine on transmembrane action potentials as related to the change in external potassium concentrations in guinea pig papillary muscle

We studied the effects of 4.8 muM prenylamine on transmembrane potentials in isolated guinea pig papillary muscles using a conventional microelectrode technique and compared them with those of 36.9 microM lidocaine. Prenylamine reduced Vmax at 1 Hz increasingly as the external potassium, [K]o, was increased from 2.7 to 10 mM. The reduction was also increased as the driving rate was increased from 0.25 to 5 Hz. The rate-dependent depression was less in 2.7 and 8.1 mM with 7.2 mM [Ca]o and more in 5.4 and 8.1 mM [K]o with 1.8 mM [Ca]o. Prenylamine produced a marked delay in the recovery of Vmax in premature responses inserted between constant driving stimuli at 0.25 Hz. The delay was also less in the former two, and more in the latter two media. Thus the effects of prenylamine on Vmax were more rate dependent and less [K]o-dependent than those of 36.9 microM lidocaine. At the diastolic interval of 100 ms, prenylamine depressed the overshoot, action potential duration at 0 mV level (APDo) and Vmax in premature responses more markedly than did 36.9 microM lidocaine, the differences of the effects being more significant for the first two. The results are interpreted as representing the calcium-antagonistic property of prenylamine of which lidocaine appears to be devoid.


Effects of tocainide and lidocaine on the transmembrane action potentials as related to external potassium and calcium concentrations in guinea-pig papillary muscles


Effects of mexiletine on transmembrane action potentials as affected by external potassium concentration and by rate of stimulation in guinea-pig papillary muscles

Clinical and Experimental Pharmacology & Physiology


Cerebral circulatory and metabolic stimulation with nitrous oxide in the dog


Modification of the relationship between cerebral metabolism, blood flow, and electroencephalogram by stimulation during anesthesia in the dog


Role of the O-linked -N-acetylglucosamine in the Cardioprotection Induced by Isoflurane


Roles of left atrial appendage for left atrial hemodynamics by left atrial appendage clamping during cardiac surgery.