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.
Acetylcholine ; Anesthesia ; Animals ; Coronary Vessels ; Dogs* ; Endothelium* ; Free Radicals ; Halothane ; Ischemia ; Lipid Peroxidation ; Malondialdehyde ; Midazolam ; Myocardial Ischemia ; Myocardial Stunning* ; Myocardium ; Nitroprusside ; Propofol* ; Reperfusion ; Stroke ; Ventricular Pressure

Endothelin (ET), a vascular endothelium derived contracting factor, provokes a strong and long lasting contraction of blood vessels, including coronary artery. Chemical stirnuli such as Ca++ ionophore (in vitro) and myocardial ischemia (in vivo) are known to promote the production of ET. Since halothane has recently been shown to block Ca++ channel, it might blunt ET-1 release or production from ischemic myocardium. To test this hypothesis, open-chest dogs underwent eitber 15 minutes (n=7) of the left anterior descending coronary artery (LAD) occlusion or 30 minutes (n=7) and 120 minutes of reperfusion under the halothane anesthesia. Plasma concentration of ET-1 in the femoral artery (FA) and the great cardiac vein (CV) draining ischemic myocardium was measured using radioimmunoas-say. ET-1 production (pg/mL) was calculated by substrating the ET-1 levels in FA from those in CV. The results were as follows; 1) Baseline ET-1 levels in FA and CV were similar in both groups. 2) ET-1 levels in FA and CV remained unchanged during myocardial ischemia in both groups. 3) ET-1 production significantly increased from baseline at 30, 60 and 120 min into reperfusion, respectively, in the 30 min group, whereas no significant changes were observed from baseline in the 15 min group. These findings indicate that halothane may blunt, but could not block the production or release of ET-1 completely during myocardial ischemia-reperfusion, especially in the case of prolonged coronary arterial occlusion.
Anesthesia ; Animals ; Blood Vessels ; Coronary Circulation* ; Coronary Vessels ; Dogs* ; Endothelin-1* ; Endothelins ; Endothelium, Vascular ; Femoral Artery ; Halothane* ; Myocardial Ischemia ; Myocardium ; Plasma ; Reperfusion ; Veins