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.

American Journal of Physiology, Heart and Circulatory Physiology


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.


Transesophageal echocardiography for intraoperative management of the fenestrated Fontan procedure.

Journal of Cardiothoracic and Vascular Anesthesia


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

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


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

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


Autotransfusion performed on a patient with cis AB blood group.

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


Pulmonary hemodynamics --- Intraoperative assessment with transesophageal Doppler echocardiography


The feasibility of gastrothoracic ventricular pacing during transesophageal echocardiography.

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


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


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

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


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


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

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


Effects of nicardipine on ventriculo-arterial coupling in humans.

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


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


ChatGPTs performance on JSA-certified anesthesiologist exam


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