Effects of Intracoronary Propofol on Functional Recovery of Stunned Myocardium and Coronary Endothelium in Dogs / 대한마취과학회지

BACKGROUND: Oxygen-derived free radicals are known to contribute to tissue injury during myocardial ischemia and reperfusion. Recent in vitro studies have shown that propofol has potent antioxidant properties. The present study was aimed to investigate the effects of propofol on recovery of mechanical and coronary endothelial function in a myocardial stunning model. METHODS: Thirty-five dogs were acutely instrumented under halothane anesthesia to measure aortic and left ventricular pressure, pulmonary and left anterior descending coronary artery (LAD) flow, and subendocardial segment length. After completion of the surgery, halothane was replaced by fentanyl- midazolam. Animals were then subjected to 15 min of LAD occlusion and 3 hrs of reperfusion under either intracoronary (i.c.) propofol (5 microgram/mL, n=11; 20 microgramg/mL LAD flow, n=12) or vehicle (saline, n=12) for 1 hr beginning 30 min before LAD occlusion. Percent segment shortening (%SS) and the slope of the preload recruitable stroke work (Mw), as an index of regional myocardial contractility, and peak lengthening rate (dL/dtmax) and percent post-systolic shortening (%PSS), as an index of regional diastolic function, were evaluated. Coronary endothelial function was assessed by examining LAD flow response to i.c. acetylcholine (ACh, 1 microgram over I min) and i.c. sodium nitroprusside (SNP, 20 microgram over I min). The myocardial content of malondialdehyde (MDA) from LAD area was measured to evaluate lipid peroxidation. RESULTS: Despite equally severe ischemic dysfunction during LAD occlusion, recovery of %SS was significantly improved during reperfusion by either dose of propofol compared to controls. However, Mw recovered to the baseline within 60 min of reperfusion in all three groups. In addition, propofol-treated dogs showed better recovery of both indices of regional diastolic function (dL/dtmax and %PSS) as compared to controls. Ischemia-reperfusion similarly attenuated the increases in the LAD flow by ACh in all the groups, whereas it had no significant effect on these increases in LAD flow by SNP. The increase in MDA induced by ischemia and reperfusion was significantly suppressed by either dose of propofol. CONCLUSIONS: The results indicate that propofol attenuates mechanical but not coronary endothelial dysfunction in postischemic, reperfused myocardium in an open-chest canine model. The protective action of propofol against mechanical dysfunction is probably due to its effect to reduce lipid peroxidation.

Effects of Acute Myocardial Ischemia on Regional Function of the Remote Nonischemic Myocardium in Dogs / 대한마취과학회지

INTRODUCTION: During an acute myocardial ischemia, maintenance of overall ventricular function may depend on remote nonischemic myocardium. Whereas fentanyl has minimal hemodynamic effects, volatile anesthetics, including halothane and isoflurane cause negative inotropic and lusitropic effects in normal myocardium. This investigation examined the effects of volatile anesthetics in comparision with fentanyl on compensatory responses to brief left anterior descending coronary artery (LAD) occlusion in remote normal myocardium (left circumflex coronary artery (LCX) supply) in an open-chest canine model. METHODS: Thirty-six mongrel dogs, acutely instrumented for measurement of pressure (left ventricle (LV) and aorta), flows (pulmonary trunk and LCX) and dimensions in ischemic and non-ischemic myocardium, were subjected to a 10-min LAD occlusion during fentanyl (n=10), halothane (n=13), or isoflurane (n=13) anesthesia. Regional contractile function was assessed using percent systolic shortening (%SS) and the preload recruitable stroke work slope (Mw). Diastolic function was evaluated using a regional time constant for intramyocardial pressure decline of LV (IMPtau), peak lengthening rate (dL/dtmax) and a regional chamber stiffness constant (Kp). RESULTS: Acute LAD occlusion caused immediate deterioration of anterior wall function similarly without changes in cardiac index, mean arterial pressure and dP/dtmax in all three groups. LV end-diastolic pressure (LVEDP), LVPtau, and heart rate increased and dP/dtmin decreased to the same extent with regional myocardial ischemia in all groups. During fentanyl anesthesia, acute myocardial ischemia was associated with an increase in %SS (26%) and Mw (48%) in LCX area without changes in IMPtau and dL/dtmax. With halothane or isoflurane anesthesia, %SS, Mw and IMPtau showed similar changes as those in fentanyl in response to LAD occlusion. However, dL/dtmax was increased (47 and 45% in the halothane and isoflurane groups, respectively) and Kp was increased (34 and 33% in the halothane and isoflurane groups, respectively) less compared to fentanyl (78%). Enhanced function in LCX zone was associated with a comparable increase (21~28% from baseline) in LCX flow in all groups. CONCLUSION: Enhanced regional contractility following acute coronary occlusion in nonischemic myocardium during fentanyl anesthesia is well-preserved with volatile anesthetics in an open-chest canine model. In addition, diastolic functions are also enhanced rather than depressed during anesthesia with volatile anesthetics. Halothane and isoflurane, however, do not differ in the compensatory responses to acute regional ischemia.