Trends and Factors Affecting the Number of Abstracts at the Annual Meeting of the Japanese Society of Anesthesiologists

日本麻酔科学会年次学術集会における一般演題数の推移と要因


Ketamine as an Alternative Anesthetic for Augmenting Seizure Durations During Electroconvulsive Therapy: A Retrospective Observational Study

Electroconvulsive therapy (ECT) is highly effective for severe psychiatric disorders; however, short seizure durations may lead to ineffective therapy. This retrospective study aimed to examine the risks and benefits of switching to ketamine anesthesia to augment seizure durations during an acute course of ECT. We included 33 patients who underwent ketamine anesthesia due to suboptimal seizures during an acute course of ECT. We assessed seizure duration, stimulus dose, hemodynamic variability, and postseizure complications before and after switching to ketamine. Age was significantly associated with suboptimal seizures during ECT (P = 0.040). After switching to ketamine, 32 patients (97%) experienced prolonged seizure duration. Ketamine significantly prolonged both electroencephalogram and motor seizure durations with a mean difference of 34.6 seconds (95% confidence interval [CI], 26.4-42.7 seconds; P < 0.001) and 26.6 seconds (95% CI, 19.6-33.6 seconds; P < 0.001), respectively. It also significantly reduced stimulus dose (mean difference, -209.5 mC [95% CI, -244.9 to -174.1 mC]; P < 0.001). In addition, maximum changes in systolic blood pressure and heart rate during ECT sessions significantly increased with ketamine (mean difference, 27.2 mm Hg [95% CI, 12.0-42.4 mm Hg; P = 0.001]; 25.7 beats per minute [95% CI, 14.5-36.8 beats per minute; P < 0.001], respectively). Patients reported more headaches with ketamine (P = 0.041). Our results provide evidence that ketamine as an alternative anesthetic can augment seizure durations in specific patients experiencing suboptimal seizures during an acute course of ECT. However, its use requires greater attention to circulatory management and postseizure complications.


The Safety and Strategies for Reinitiating Electroconvulsive Therapy After ECT-Induced Takotsubo Cardiomyopathy: A Case Report and Systematic Review.

Electroconvulsive therapy-induced TCM is more likely to cause cardiogenic shock than nonperioperative cases; nevertheless, it has good prognosis. Cautious reinitiation of ECT after TCM recovery is possible. Further studies are required to determine preventive measures for ECT-induced TCM.


Hemodynamic impact of ephedrine on hypotension during general anesthesia: a prospective cohort study on middle-aged and older patients

Ephedrine is a mixed α- and β-agonist vasopressor that is frequently used for the correction of hypotension during general anesthesia. β-responsiveness has been shown to decrease with age; therefore, this study aimed to determine whether aging would reduce the pressor effect of ephedrine on hypotension during general anesthesia. Seventy-five patients aged ≥ 45 years were included in this study, with 25 patients allocated to each of the three age groups: 45-64 years, 65-74 years, and ≥ 75 years. All patients received propofol, remifentanil, and rocuronium for the induction of general anesthesia, followed by desflurane and remifentanil. Cardiac output (CO) was estimated using esCCO technology. Ephedrine (0.1 mg/kg) was administered for the correction of hypotension. The primary and secondary outcome measures were changes in the mean arterial pressure (MAP) and CO, respectively, at 5 min after the administration of ephedrine. RESULTS: The administration of ephedrine significantly increased MAP (p < 0.001, mean difference: 8.34 [95% confidence interval (CI), 5.95-10.75] mmHg) and CO (p < 0.001, mean difference: 7.43 [95% CI, 5.20-9.65] %) across all groups. However, analysis of variance revealed that the degree of elevation of MAP (F [2, 72] = 0.546, p = 0.581, η = 0.015 [95% CI, 0.000-0.089]) and CO (F [2, 72] = 2.023, p = 0.140, η = 0.053 [95% CI, 0.000-0.162]) did not differ significantly among the groups. Similarly, Spearman's rank correlation and multiple regression analysis revealed no significant relation between age and the changes in MAP or CO after the administration of ephedrine. The administration of ephedrine significantly increased MAP and CO; however, no significant correlation with age was observed in patients aged > 45 years. These findings suggest that ephedrine is effective for the correction of hypotension during general anesthesia, even in elderly patients. UMIN-CTR (UMIN000045038; 02/08/2021).


Relative publication output and international collaboration in anaesthesiology and pain medicine: a bibliometric analysis from 1996 to 2021


Authorship by gender in anesthesiology journals: a retrospective cross-sectional study for Japan

Although it is important to recognize gender disparities in publishing to achieve gender diversity, women's authorship in Japan remains unclear. Therefore, this study aimed to investigate the percentage and analyze the trends of articles authored and published in anesthesiology journals by Japanese female authors. The genders of the first and last authors affiliated with Japanese institutions were surveyed in the Journal of Anesthesia (JA) (1990, 1995, and 2000-2022) and 11 international anesthesiology journals (2010-2022). We included 845 and 819 original research articles from JA in the analyses of the first and last authors, respectively. The proportion of female first authors significantly increased from 41 (11.7%) out of 351 before 2009 to 119 (24.1%) out of 494 after 2010 (p < 0.001). The proportion of female last authors was 11 (3.3%) out of 335 before 2009 and 22 (4.5%) out of 484 after 2010, respectively, with no significant difference (p = 0.470). We included 624 and 572 original research articles from international anesthesiology journals in the analyses of first and last authors, respectively. Among these, there were 134 (21.5%) and 23 (4.0%) female first and last authors, respectively. These proportions in international anesthesiology journals did not significantly differ from those in JA (p = 0.334, p = 0.789, respectively). The percentage of female first authors has increased, commensurate with the percentage of female anesthesiologists. However, the percentage of female last authors has not increased and remains low in Japan.


Comparison of hemodynamics during induction of general anesthesia with remimazolam and target-controlled propofol in middle-aged and elderly patients: a single-center, randomized, controlled trial.

MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (- 41.1 [16.4] mmHg and - 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: - 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (p = 0.341).


General Anesthesia in a Patient With Neuronal Intranuclear Inclusion Disease: A Case Report.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease with diverse clinical manifestations, including dementia and muscle weakness. We summarize anesthetic considerations in reporting general anesthesia for a 58-year-old man with bladder dysfunction and cerebellar ataxia who was diagnosed with NIID. The patient developed postinduction hypotension relevant to autonomic neuropathy. The potential risks, such as prolonged reaction to neuromuscular blocking agent, postoperative delirium, and worsening of NIID-related symptoms, were also considered. The responsiveness to anesthetics may vary widely from case t case. As the number of NIID cases increases, a better understanding of NIID is needed.


Transition in eye gaze as a predictor of emergence from general anesthesia in children and adults: a prospective observational study.

In children, eye-gaze transition was observed significantly earlier than other physical-behavioral responses during emergence from general anesthesia and seemed to reflect emergence from anesthesia. In contrast, observation of eye gaze was not a useful indicator of emergence from anesthesia in adults.


Impact of surgical masks on fraction of inspired oxygen during oxygen therapy depends on the type of oxygen masks and respiratory conditions: volunteer- and simulation-based studies.

during oxygen therapy with oxygen masks. The impact of SM depended on the type of the oxygen mask, mask fitting, and respiratory condition.

was measured using a simulator that reproduced spontaneous breathing. RR was 12 or 24 bpm, and the tidal volume (Tv) was 300, 500, or 700 mL. The effect of oxygen mask fitting conditions was also examined. The primary outcome measure was FIO


Elevated tryptase in vancomycin-induced red man syndrome.


Assessment of accidental events in images during capsule endoscopy

当院における カプセル内視鏡検査の画像不良事例と対策について

Recently, there have been some reports of electromagnetic interference during capsule endoscopy(CE)in regards to other medical devices and facility environment. These accidental events have not been analyzed sufficiently although academic societies and related ministries are proposing guidelines with cautious attention. Based on this, detailed analyses and development of solution are required. In this study, we review our experience with cases of accidental events during CE and assessed the causes and preventive solutions. A total of149CE cases(male :89, female :60, mean age :56±18 8)from January 2017 until December 2019 were analyzed retrospectively. Four cases(2%)with defective images were noted. Detailed events were as follows ;1 disorder of the sensor array, 2 recorder freezes, and 1 electromagnetic interference. These mechanical and electromagnetic troubles should be assessed and shared among medical staffs and manufacturers to propose possible solutions and perform CE safely.


Assessment of postoperative nutritional status and physical function between open surgical aortic valve replacement and transcatheter aortic valve implantation in elderly patients.

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even. J. Med. Invest. 67 : 139-144, February, 2020.

The Journal of Medical Investigation : JMI


Ultrasound-guided Peripheral Nerve Block and General Anesthesia for Hepatectomy in a Patient with Chronic Inflammatory Demyelinating Polyneuropathy

慢性炎症性脱髄性多発根ニューロパチー患者に対する肝切除術の麻酔経験


Peripartum Cardiomyopathy after Cesarean Section in a Patient with Myotonic Dystrophy

帝王切開後に産褥性心筋症を発症し心不全に陥った筋緊張性ジストロフィー妊婦の麻酔経験


Postoperative nausea and vomiting following lower limb surgery :a comparison between single-injection intraarticular anesthesia and continuous epidural anesthesia.

Study Objective : the incidence of postoperative nausea and vomiting (PONV) following single-injection intraarticular anesthesia was compared to that following continuous epidural anesthesia. Design : Prospective, double-blind, randomized study. Setting : University-affiliated teaching hospital. Patients : Forty-eight patients finally participated in this study, and each group contained twenty-four patients. Interventions : Patients scheduled to undergo lower limb surgery under general anesthesia were randomly allocated into two groups, to receive either single-injection intraarticular or continuous epidural anesthesia for postoperative analgesia. Measurements : The incidence and severity of PONV, complete response rates (i.e., no vomiting or rescue antiemetic use), and pain scores were recorded 2, 24, and 48 h postoperatively. Main results : No significant differences between groups were observed in the incidence and severity of PONV, rescue antiemetic use, or complete response rate at any of the time points, but only the use of rescue analgesics was significantly less in continuous epidural anesthesia group during the 2-24h postoperative period (P=0.04). Conclusion : While the use of single-injection intraarticular anesthesia following lower limb surgery did not prevent PONV more than continuous epidural anesthesia in this study, the intraarticular technique still provides greater simplicity, safety, and cost-effectiveness. J. Med. Invest. 66 : 303-307, August, 2019.


Anesthetic management of a patient with methylmalonic acidemia: a case report.

Methylmalonic acidemia (MMA) is a metabolic disorder of organic acids and is characterized by the accumulation of methylmalonic acids. The patient was a 19-year-old female diagnosed with severe MMA at 3 days of age, who was scheduled for renal replacement therapy. Preoperatively, there was no evidence of metabolic acidosis or electrolyte abnormalities. Glucose was administered preoperatively following a 6-h fast. Anesthesia was administered using thiamylal, remifentanil, rocuronium, and sevoflurane. After tracheal intubation, the patient underwent an ultrasound-guided bilateral rectus sheath block with ropivacaine. A drop in blood sugar level was treated with 5% glucose. Extubation was performed after intravenous administration of sugammadex. We report the anesthetic management of a patient with MMA using a combination of general anesthesia and rectus sheath block.


The Efficacy of Programmed Intermittent Epidural Bolus for Postoperative Analgesia after Open Gynecological Surgery: A Randomized Double-Blinded Study.

It is well known that the programmed intermittent epidural bolus (PIEB) technique effectively provides epidural anesthesia in labor. This randomized double-blind trial compared the postoperative analgesic efficacy of PIEB with that of continuous epidural infusion (CEI) in patients undergoing gynecological surgery under combined general-epidural anesthesia. Patients undergoing open gynecological surgery under combined general-epidural anesthesia were randomized at a 1 : 1 ratio to receive PIEB or CEI. In the PIEB group, the pump delivered 4L ropivacaine 0.2% plus fentanyl 2 g/mL every hour. In the CEI group, the pump delivered the same solution at a rate of 4L/h. In both groups, additional 4L boluses of ropivacaine 0.2% plus fentanyl 2 g/mL were provided, when necessary, by patient-controlled epidural analgesia after surgery. The primary outcome was the total ropivacaine dose 40 hours after surgery. The secondary outcomes were the number of PCEA boluses and postoperative pain (evaluated on an 11-point numerical rating scale) 3, 24, and 48 hours after surgery. In total, 57 patients were randomized ( = 28 and 29 in the PIEB and CEI groups, resp.). The two groups differ significantly in terms of the total ropivacaine dose 40 hours after surgery (mean (standard deviation): 155.38 (4.55) versus 159.73 (7.87)L, = 0.016). Compared to the CEI group, the PIEB group had significantly lower numerical rating scale scores 3 hours (median [lower-upper quartiles]: 0 [0-0.5] versus 3 [0-5.5], = 0.002), 24 hours (1 [0-2] versus 3 [1-4], = 0.003), and 48 hours (1 [0-2] versus 2 [2-3.5], = 0.002) after surgery. PIEB was better than CEI in terms of providing postoperative analgesia after open gynecological surgery under combined general-epidural anesthesia.


Jelly-type carbohydrate supplement in healthy subjects suppresses the catabolism of adipose tissue and muscle protein and improved their satisfactions.


Effectiveness of using non-invasive continuous arterial pressure monitoring with ClearSight in hemodynamic monitoring during living renal transplantation in a recipient:a case report.

We investigated the effectiveness of the ClearSight system for hemodynamic management during kidney transplantation for a recipient. The recipient was to receive a kidney transplant from his mother under general anesthesia. We used continuous noninvasive finger-cuff-based monitoring of blood pressure, provided by the ClearSight system, and stroke volume variation to predict fluid responsiveness. We used of a balanced anesthetic technique and stringent monitoring standards to ensure a successful outcome for the patient. This case demonstrated that ClearSight has the potential to improve patient monitoring in hemodynamically stable patients who received kidney transplantation under general anesthesia. J. Med. Invest. 65:139-141, February, 2018.


Noninvasive continuous blood pressure monitoring by the ClearSight system during robot-assisted laparoscopic radical prostatectomy.

Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.


A comparison of fosaprepitant and ondansetron for preventing postoperative nausea and vomiting in moderate to high risk patients: A retrospective database analysis.

Postoperative nausea and vomiting (PONV) occur in 30-50% of patients undergoing general anesthesia and in 70-80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, = 82) and intravenous ondansetron 4 mg (ONS group, = 89) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0-2, 0-24, and 0-48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0-48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0-48 hours after surgery.


Normothermic Cardiopulmonary Bypass in Patient with Waldenstroms Macroglobulinemia and Cryoglobulinemia: A Case Report.

Waldenström's macroglobulinemia (WM) manifests as hyperviscosity syndrome. Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in association with decreased body temperature, can occur in combination with WM. We describe the management of an 82-year-old woman with WM, hyperviscosity syndrome, and cryoglobulinemia who required open aortic valve replacement. Decreased body temperature in this patient was prevented during cardiopulmonary bypass by using a forced air warming system and normothermic cardioplegia with continuous warm blood cardioplegia perfusion.


Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers.

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.


Phosphatidylinositol 3-kinase inhibition induces vasodilator effect of sevoflurane via reduction of Rho kinase activity.

This study was aimed to examine whether a volatile anesthetic sevoflurane in clinical doses reduces vasoconstriction under the inhibition of phosphatidylinositol 3-kinase (PI3K) in the rat and human arteries and whether the intravenous administration of the PI3K inhibitor decreases blood pressure in rats under the sevoflurane inhalation. Rat arteries (n=5-6) and human omental arteries (n=5-6) were subjected to isometric force recordings and western immunoblotting for Rho kinase, mitogen-activated protein kinase, and protein kinase C. Some arteries were incubated with sevoflurane (1.5% or 3%), a selective PI3K inhibitor LY294002 (3×10mol/L) or the combination. Mean arterial pressure (MAP) and heart rate (HR) in rats (n=7) were evaluated with or without intravenous injection of LY294002 (3×10mol/L) under 2% sevoflurane inhalation. Sevoflurane with LY294002, but not sevoflurane or LY294002 solely, inhibited the phenylephrine-induced contraction (32% to 52% decrease at phenylephrine [3×10mol/L] in rat arteries and [3×10mol/L] in human arteries). Sevoflurane (3%) only with LY294002 decreased Rho kinase activity in the rat aorta into 30%. Intravenous LY294002 reduced MAP (8.1-12.4mmHg decrease), but not HR, in rats under 2% sevoflurane inhalation. Clinical sevoflurane doses with PI3K inhibition reduce the contraction of rat and human arteries ex vivo resulting from Rho kinase inhibition, and systemic blood pressure of rats in vivo. These results suggest that sevoflurane potentially causes vasodilation and hypotension in patients receiving anti-cancer therapy that inhibits PI3K.


Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.


Anesthetic management of a patient with unruptured sinus of valsalva aneurysm with right ventricular outflow tract obstruction.


General anesthesia of a Japanese infant with Barber-Say syndrome: a case report


Plasma substance P concentrations in patients undergoing general anesthesia: an objective marker associated with postoperative nausea and vomiting

This study investigated plasma concentrations of substance P (SP) in patients undergoing general anesthesia (GA) and postoperative nausea and vomiting (PONV). This prospective, observational, cohort study included 23 patients who underwent scheduled surgery under general anesthesia. Blood was collected from the radial artery at predetermined time points (15-30 mins prior anesthesia, 15-30 mins after surgery/GA, and 24 h after surgery). PONV, SP concentrations, risk factors, and analgesics used were measured. Nine of 23 patients experienced PONV. In patients without PONV, SP concentrations significantly decreased ( < 0.0001) at the end of surgery/GA, compared to baseline, and recovered at 24 h after surgery/GA (452.9 ± 146.2 vs. 666.9 ± 176.5 vs. 580.7 ± 168.6 pg/mL, respectively), whereas SP levels were unchanged during surgery/GA and increased at 24 hours after surgery ( = 0.020) in patients with PONV (726.1 ± 167.8 vs. 655.8 ± 168.0 vs. 779.7 ± 220.7 pg/mL, respectively). These finding suggest that SP levels may be utilized as an objective marker for PONV.


The synergistic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice.


Isoflurane-induced postconditioning via mitochondrial calcium-activated potassium channels.

Activation of the mitochondrial calcium-activated potassium (mKCa) channel reportedly confers resistance to myocardial ischemic stress. However, the role of the mKCa channel in postconditioning induced by volatile anesthetic remains unclear. Male Japanese white rabbits underwent coronary artery occlusion for 30 min followed by reperfusion for 3 h. Volatile anesthetic, isoflurane, was administered at 3 min prior to reperfusion for 5 min. Rabbits were injected with the mKCa channel blocker, iberiotoxin, or the mKCa channel opener, NS1619, at 8 min prior to reperfusion. Myocardial infarct size and the area at risk (AAR) were measured at the end of the experiment. Isoflurane significantly reduced infarct size (23.0 ± 9.8% of the AAR, P<0.05) compared with the control (44.0 ± 9.1%). Iberiotoxin abolished the cardioprotective impact of isoflurane (43.0 ± 11.6%), while iberiotoxin alone exerted no effect on infarct size (45.0 ± 9.5%). NS1619 and isoflurane/NS1619 both significantly reduced infarct size (21.0 ± 10.3% and 19.0 ± 8.8%, respectively, P<0.05 vs control group), but isoflurane/NS1619 showed no additional benefits compared with isoflurane alone. These results indicate that activation of the mKCa channel contribute isoflurane-induced postconditioning.

The Journal of Medical Investigation : JMI


Role of transesophageal echocardiography during biventricular pacemaker implantation in children


[Effects of a novel method of anesthesia combining propofol and volatile anesthesia on the incidence of postoperative nausea and vomiting in patients undergoing laparoscopic gynecological surgery].

We investigated the effects of a novel method of anesthesia combining propofol and volatile anesthesia on the incidence of postoperative nausea and vomiting in patients undergoing laparoscopic gynecological surgery. Patients were randomly divided into three groups: those maintained with sevoflurane (Group S; n = 42), propofol (Group P; n = 42), or combined propofol and sevoflurane (Group PS; n = 42). We assessed complete response (no postoperative nausea and vomiting and no rescue antiemetic use), incidence of nausea and vomiting, nausea severity score, vomiting frequency, rescue antiemetic use, and postoperative pain at 2 and 24h after surgery. The number of patients who exhibited a complete response was greater in Groups P and PS than in Group S at 0-2h (74%; 76% and 43%; respectively, p = 0.001) and 0-24h (71%; 76%, and 38%; respectively, p < 0.0005). The incidence of nausea at 0-2h (Group S = 57%; Group P = 26% and Group PS = 21%; p = 0.001) and 0-24h (Group S = 62%; Group P = 29% and Group PS = 21%; p < 0.0005) was also significantly different among groups. However, there were no significant differences among groups in the incidence or frequency of vomiting or rescue antiemetic use at 0-24h. Combined propofol and volatile anesthesia during laparoscopic gynecological surgery effectively decreases the incidence of postoperative nausea.


Fosaprepitant versus ondansetron for the prevention of postoperative nausea and vomiting in patients who undergo gynecologic abdominal surgery with patient-controlled epidural analgesia: a prospective, randomized, double-blind study.

Compared to ondansetron, fosaprepitant more effectively decreased the incidence of vomiting in patients who underwent gynecologic abdominal surgery with patient-controlled epidural analgesia.

No (0 %) patient in the NKI group experienced vomiting after surgery; however, 4-6 (20-30 %) of 20 patients in the ONS group experienced vomiting. This difference was significant at 0-24, 0-48, and 0-72 h. During the study period, no significant differences existed between the NK1 and ONS groups in the incidence of PONV, complete response rate, rescue antiemetic use, nausea score, and VAS score for pain.


Geranylgeranylacetone and volatile anesthetic-induced cardiac protection synergism is dependent on caveolae and caveolin-3.

Pharmacological preconditioning, including that with geranylgeranylacetone (GGA) and volatile anesthetics, has been shown to confer cardiac protection from ischemia/reperfusion injury although the mechanisms for this protection are poorly understood. Caveolins, integral membrane proteins that act as scaffolding proteins in caveolar membranes, localize molecules involved in cardiac protection. We have tested the hypothesis that caveolin-3 (Cav-3), the predominant isoform in cardiac myocytes, is essential for the synergistic effect observed between GGA and volatile anesthetics. Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts. Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0 % of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4 %; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1 % (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane. Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.


ラリンゴブロック喉頭鏡のその後

ラリンゴブロック喉頭鏡のその後


主観的包括的評価(SGA)の結果よりみる周術期栄養状態の実態

主観的包括的評価(SGA)の結果よりみる周術期栄養状態の実態


Perineural but not systemic low-dose dexamethasone prolongs the duration of interscalene block with ropivacaine: a prospective randomized trial.

To determine the effects of intravenous and perineural dexamethasone on the duration of interscalene brachial plexus block (ISB) with ropivacaine in patients undergoing arthroscopic shoulder surgery. In this prospective, randomized, placebo-controlled trial, patients presenting for arthroscopic shoulder surgery with an ISB were randomized to receive ropivacaine 0.75% (group C), ropivacaine 0.75% plus perineural dexamethasone 4 mg (group Dperi), or ropivacaine 0.75% plus intravenous dexamethasone 4 mg (group Div). The primary outcome was the duration of analgesia, defined as the time between performance of the block and the first request for analgesic. Thirty-nine patients were randomized. The median times of sensory block in groups C, Dperi, and Div were 11.2 hours (interquartile range [IQR] 8.0-15.0 hours), 18.0 hours (IQR 14.5-19.0 hours), and 14.0 hours (IQR 12.7-15.1 hours), respectively. Significant differences were observed between groups Dperi and C (P=0.001). Kaplan-Meier analysis for the first analgesic request showed significant differences between groups Dperi and C (P=0.005) and between groups Dperi and Div (P=0.008), but not between groups C and Div. Perineural but not intravenous administration of 4 mg of dexamethasone significantly prolongs the duration of effective postoperative analgesia resulting from a single-shot ISB with ropivacaine 0.75%.


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.


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.


Overfeeding induces protein catabolism and nutritional stress in critical ill patients.

重症患者の栄養療法に起因する代謝性有害反応―エネルギーの過剰投与による筋タンパク異化と栄養ストレス―

Purpose: Overfeeding is known to induce metabolic problems in critical ill patients as well as malnutrition. In this study, we have determined the effect of overfeeding on protein catabolism as nutritional stress.Subjects and Methods: Analyses were evaluated for metabolic status. 30 patients in a hospital ICU and receiving mechanical ventilation were measured energy expenditure by using indirect calorimetry. Patients were divided into 3 groups: underfeeding (U), adequate feeding (A), overfeeding (O). Energy expenditure, 3-methyl-histidine, creatinine, blood urea nitrogen, noradrenalin, C-reactive protein, prealbumin levels were assessed.Results: The assessment of protein catabolism using 3-methyl-histidine/creatinine indicated that patients with overfeeding were prompt catabolism. BUN, CRP and prealbumin were not different among each group. The patients with overfeeding showed high level of urea noradrenalin significantly compared with other groups. However, length of ICU stay and ventilated duration were not changed between each group. Feeding routes; enteral nutrition, parental nutrition or both of those, did not make significant difference of protein catabolism and nutritional stress.Conclusion: Overfeeding induced protein catabolism since it might be from nutrition stress.

【目的】本研究では，エネルギーの過剰投与が筋タンパク異化および栄養ストレスに与える影響について検討した．【対象及び方法】対象は，当院ICUに入室した患者のうち呼吸管理を必要とする患者30名とした．エネルギー消費量を測定し，投与エネルギー量と比較して投与不足となっている群 (U群)，両者がほぼ一致している適正群 (A群)，過剰投与となっている群 (O群) の3群に分け比較検討した．【結果】尿中クレアチニン量による補正尿中3-メチルヒスチジン値及び尿中ノルアドレナリン値はU・A群に有意差はなかったが，O群では有意に増加していた．さらに，尿中3-メチルヒスチジン値と尿中ノルアドレナリン値の間に相関関係が認められた．【結論】エネルギーの過剰投与により筋タンパクの異化が亢進するとともに，ノルアドレナリンの分泌に伴う栄養ストレスが筋タンパク分解を促進させることが明らかとなった．


ラリンゴブロック喉頭鏡を使用した気管挿管における有用性の検討

ラリンゴブロック喉頭鏡を使用した気管挿管における有用性の検討


整形外科病棟における術前経口補水液の導入とその効果

整形外科病棟における術前経口補水液の導入とその効果

Japanese Journal of Nutritional Assessment


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


Anesthesia for deep brain stimulation in a patient with X-linked dystonia-parkinsonism/Lubag disease.

Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. This disease is characterized by dystonia dominating the first 10-15 years of the disorder, which is associated with or replaced by parkinsonian features in later years of life. A 49-year-old man with Lubag disease underwent general anesthesia for deep brain stimulation (DBS) surgery. Anesthesia was maintained mainly with propofol, remifentanil, rocuronium bromide, and sevoflurane. During magnetic resonance imaging, the patient was anesthetized with midazolam, fentanyl, and rocuronium bromide. The surgery was completed safely using these anesthetic agents. After DBS, some symptoms including involuntary movement improved within 10 days.

The Journal of Medical Investigation : JMI


Two Cases of Anaphylactoid Reaction after Administration of Sugammadex

スガマデクス投与後にアナフィラキシー様反応を呈した2症例

Anaphylaxis during anesthesia is a rare but life-threatening event. Sugammadex is a recently introduced drug that was specifically designed for the reversal of rocuroium and vecuronium-induced neuromuscular block. We describe the cases of a 74-year-old man and a 29-year-old man who developed an anaphylactoid reaction to sugammadex, presenting with cardiovascular collapse. Initial management consisted of fluid administration and intermittent i.v. ephedrine, epinephrine, and hydrocortisone. The patients made uncomplicated recovery and were discharged.


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.


Biophysical and Pharmacological Properties of Glucagon-Like Peptide-1 in Rats Under Isoflurane Anesthesia.

Glucagon-like peptide-1 (GLP-1) increases insulin secretion and has an important role in maintaining glucose homeostasis. In this study, we evaluated the biophysical and pharmacological properties of GLP-1 by performing in vivo and in vitro experiments to determine the applicability of GLP-1 in glycemic control in rats under isoflurane anesthesia. Levels of portal GLP-1, insulin, and glucose and dipeptidyl peptidase-4 activity were measured in the basal fasting state and after gastric glucose load before, during, and after exposure to 30% O(2) in air (control) or 1.4% isoflurane in a mixture of 30% O(2) and air. The direct effects of isoflurane on GLP-1 secretion were assessed in human enteroendocrine NCI-H716 cells. Insulin release from isolated pancreatic islets was measured using a radioimmunoassay. Single pancreatic β-cell membrane potentials were recorded using whole-cell current-clamp patches perforated by β-escin. In fasting rats, inhalation of isoflurane led to a decrease in the basal levels of GLP-1 but did not affect insulin and glucose levels. Levels of GLP-1, insulin, and glucose increased after gastric administration of glucose in control rats. However, isoflurane attenuated the glucose-induced increase in GLP-1 and insulin levels and increased plasma glucose levels. In contrast, isoflurane did not affect dipeptidyl peptidase-4 activity before or after gastric glucose loading. Isoflurane (0.35 mM) inhibited GLP-1 release in NCI-H716 cells; this finding was similar to that observed in in vivo studies. In perifusion experiments, isoflurane (0.35 mM) inhibited glucose-induced insulin release, whereas exogenous GLP-1 (10 nM) enhanced insulin release. Importantly, combined administration of isoflurane and GLP-1 enhanced both phases of glucose-induced insulin release to an extent similar to that achieved with GLP-1 alone. Whole-cell patches showed that exposure to GLP-1 (10 nM) led to nearly complete restoration of glucose-stimulated depolarization that had been suppressed by isoflurane (0.35 mM). GLP-1 secretion is impaired during isoflurane anesthesia. However, our study showed that the insulinotropic action of GLP-1 was not affected by isoflurane. Furthermore, exposure to GLP-1 increased the membrane activity of pancreatic β-cells, preventing isoflurane-induced impairment of glucose-induced insulin secretion. These results support the hypothesis that GLP-1-based therapy may be a useful approach for achieving intraoperative glycemic control.


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.


Emergency Anesthesia in a Patient with von Hippel-Lindau Syndrome Who Underwent Pheochromocytectomy and the Resection of Cerebellar Hemangioblastoma

脳血管芽腫摘出術と褐色細胞腫摘出術を緊急で行ったvon Hippel-Lindau病の麻酔経験

The Journal of Japan Society for Clinical Anesthesia


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.


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.


A case where rocuronium was unable to achieve neuromuscular block immediately after sugammadex administration.

We present a case where immediate muscle relaxation was needed following sugammadex administration. A 72 year-old female underwent surgery for a cerebral artery aneurysm. Upon conclusion of the operation sugammadex (9.3 mg/kg) was administered and the patient was noted to have left hemiplegia. Rocuronium (1.2 mg/kg × 2 doses) was given in order to gain neuromuscular block approximately 25 minutes after sugammadex had been injected. Although TOF monitoring was not utilized in this case and assessing residual muscular block was difficult, spontaneous respirations continued and breathing had to be controlled with sevoflurane and remifentanil. Sugammadex is a potent reversal agent for rocuronium-induced neuromuscular block, however, certain situations require immediate neuromuscular blockade following sugammadex. In this case, rocuronium was unable to induce neuromuscular blockade immediately after sugammadex and that higher concentrations were necessary in addition to intravenous analgesics and inhaled anesthetics.

The Journal of Medical Investigation : JMI


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.


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.


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.


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.


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.


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.


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.

The Journal of Medical Investigation : JMI


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.


Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction in rabbits.

Preconditioning against myocardial infarction by volatile anesthetics is well known. The authors tested the hypothesis that new emulsified formulations of halogenated anesthetics administered intravenously reduce myocardial infarct size when administered either 1 or 24 h before prolonged ischemia and reperfusion. Pentobarbital-anesthetized rabbits (n = 39) were instrumented for measurement of hemodynamics and randomly assigned to receive intravenous saline (control), lipid vehicle, or infusions (3.5 ml . kg . h for 30 min) of emulsified isoflurane (6.9%), enflurane (7.1%), or sevoflurane (7.5%). Infusions were discontinued 30 min before a 30-min coronary occlusion and 3 h of reperfusion. In three additional groups, conscious rabbits (n = 21) received saline, lipid vehicle, or emulsified sevoflurane (7.5%) infusions (3.5 ml . kg . h for 30 min) 24 h before ischemia and reperfusion. Infarct size was determined using triphenyltetrazolium staining. Lipid vehicle produced transient increases in heart rate, whereas emulsified volatile anesthetics had no effect on hemodynamics before coronary occlusion. Lipid vehicle did not affect infarct size (38 +/- 2% of the area at risk; mean +/- SEM) as compared with saline control (41 +/- 4%). In contrast, emulsified isoflurane, enflurane, and sevoflurane reduced infarct size (20 +/- 3%, 20 +/- 3%, and 21 +/- 2% of the area at risk, respectively; P < 0.05). Administration of lipid vehicle or emulsified sevoflurane did not produce sedation or respiratory depression in conscious rabbits. Emulsified sevoflurane (18 +/- 2%) but not lipid vehicle (44 +/- 2%) reduced infarct size as compared with control in delayed preconditioning experiments. Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction.


Preconditioning by isoflurane is mediated by reactive oxygen species generated from mitochondrial electron transport chain complex III.

Reactive oxygen species (ROS) mediate volatile anesthetic preconditioning. We tested the hypothesis that isoflurane (ISO) generates ROS from electron transport chain complexes I and III. Rabbits (n = 55) underwent 30 min coronary artery occlusion followed by 3 h reperfusion and received 0.9% saline, the complex I inhibitor diphenyleneiodonium (DPI; 1.5 mg/kg bolus followed by 1.5 mg/kg over 1 h), or the complex III inhibitor myxothiazol (MYX; 0.1 mg/kg bolus followed by 0.3 mg/kg over 1 h) in the absence and presence of 1.0 minimum alveolar concentration ISO. ISO was administered for 30 min and discontinued 15 min before coronary occlusion. Infarct size and ROS production (n = 32) were determined using triphenyltetrazolium staining and ethidium-DNA fluorescence, respectively. Adenosine triphosphate (ATP) synthesis in mitochondria obtained from rabbit hearts (n = 24) subjected to drug interventions was measured by luciferin-luciferase luminometry. ISO significantly (P < 0.05) reduced infarct size (19% +/- 4%) as compared with control (39% +/- 4%). MYX (35% +/- 4%), but not DPI (24% +/- 2%), abolished this protection. ISO increased ethidium-DNA fluorescence (83 +/- 11 U) as compared with control (40 +/- 12 U). MYX (35 +/- 3 U), but not DPI (78 +/- 9 U), abolished ROS generation. DPI and MYX selectively reduced complex I- and complex III-mediated ATP synthesis, respectively. ROS generated from electron transport chain complex III mediate ISO-induced cardioprotection.


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


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


Isoflurane produces delayed preconditioning against myocardial ischemia and reperfusion injury: role of cyclooxygenase-2.

Whether volatile anesthetics produce a second window of preconditioning is unclear. The authors tested the hypothesis that isoflurane causes delayed preconditioning against infarction and, further, that cyclooxygenase (COX)-2 mediates this beneficial effect. Rabbits (n = 43) were randomly assigned to receive 0.9% intravenous saline, the selective COX-2 inhibitor celecoxib (3 mg/kg intraperitoneal) five times over 2 days before coronary artery occlusion and reperfusion, or isoflurane (1.0 minimum alveolar concentration) 24 h before acute experimentation in the absence or presence of celecoxib pretreatment. Two additional groups of rabbits received a single dose of celecoxib either 30 min before or 21.5 h after administration of isoflurane. Rabbits were then instrumented for measurement of hemodynamics and underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Myocardial infarct size was measured using triphenyltetrazolium staining. Western immunoblotting to examine COX-1 and COX-2 protein expression was performed in rabbit hearts that had or had not been exposed to isoflurane. Isoflurane significantly (P < 0.05) reduced infarct size (22 +/- 3% of the left ventricular area at risk) as compared with control (39 +/- 2%). Celecoxib alone had no effect on infarct size (36 +/- 4%) but abolished isoflurane-induced cardioprotection (36 +/- 4%). A single dose of celecoxib administered 2.5 h before coronary occlusion and reperfusion also abolished the delayed protective effects of isoflurane (36 +/- 4%), but celecoxib given 30 min before exposure to isoflurane had no effect (22 +/- 4%). Isoflurane did not alter COX-1 and COX-2 protein expression. The results indicate that the volatile anesthetic isoflurane produces a second window of preconditioning against myocardial ischemia and reperfusion injury. Furthermore, COX-2 is an important mediator of isoflurane-induced delayed preconditioning.


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.


Reactive oxygen species are critical mediators of coronary collateral development in a canine model.

Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n = 8) or presence of N-acetylcysteine (NAC) (occlusion + NAC, n = 8). A sham group (n = 8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71 +/- 7%) in occlusion dogs after 21 days but remained unchanged (13 +/- 3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28 +/- 8%). Brief coronary artery occlusion and reperfusion caused ROS production (256 +/- 33% of baseline values), which was abolished with NAC (104 +/- 12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation.

American Journal of Physiology, Heart and Circulatory Physiology


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.


Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species.

Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo. Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent. The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.


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.


Mechanism of preconditioning by isoflurane in rabbits --- A direct role for reactive oxygen species

Reactive oxygen species (ROS) contribute to myocardial protection during ischemic preconditioning, but the role of the ROS in protection against ischemic injury produced by volatile anesthetics has only recently been explored. We tested the hypothesis that ROS mediate isoflurane-induced preconditioning in vivo. Pentobarbital-anesthetized rabbits were instrumented for measurement of hemodynamics and were subjected to a 30 min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive vehicle (0.9% saline), or the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptopropionyl glycine (2-MPG; 1 mg. kg(-1).min(-1)), in the presence or absence of 1.0 minimum alveolar concentration (MAC) isoflurane. Isoflurane was administered for 30 min and then discontinued 15 min before coronary artery occlusion. A fluorescent probe for superoxide anion production (dihydroethidium, 2 mg) was administered in the absence of the volatile anesthetic or 5 min before exposure to isoflurane in 2 additional groups (n = 8). Myocardial infarct size and superoxide anion production were assessed using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively. Isoflurane (P < 0.05) decreased infarct size to 24 +/- 4% (mean +/- SEM; n = 10) of the left ventricular area at risk compared with control experiments (43 +/- 3%; n = 8). NAC (43 +/- 3%; n = 7) and 2-MPG (42 +/- 5%; n = 8) abolished this beneficial effect, but had no effect on myocardial infarct size (47 +/- 3%; n = 8 and 46 +/- 3; n = 7, respectively) when administered alone. Isoflurane increased superoxide anion production as compared with control experiments (28 +/- 12 -6 +/- 9 fluorescence units; P < 0.05). The results indicate that ROS produced following administration of isoflurane contribute to protection against myocardial infarction in vivo.


Isoflurane-induced preconditioning is attenuated by diabetes.

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K(+) channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 +/- 3% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 +/- 3%; n = 8) but blocked the protective effects of 0.32% (27 +/- 2%; n = 7) and not 0.64% isoflurane (18 +/- 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.


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.


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.