A novel experimental approach will be used to compare direct cardiac effects of the volatile anesthetics, isoflurane, halothane, and enflurane. This approach avoids the pronounced systemic hemodynamic responses that complicated interpretation of previous results because of concurrent changes in myocardial work demand and activation of neural and hormonal reflex pathways. Using an extracorporeal perfusion system, the volatile anesthetics will be administered selectively into the left anterior descending coronary artery of the in situ heart of the open chest dog with hemodynamic conditions tightly controlled. Total coronary blood flow will be measured electromagnetically and its transmural distribution assessed with radioactive microspheres. Local myocardial oxygen consumption (Fick principle) and segmental shortening (sonomicrometry) will be evaluated. A primary objective of the proposed investigation is to characterize unambiguously the direct effects of the volatile anesthetics 1) on vascular tone and blood flow, oxygen consumption, and segmental shortening in normal myocardium, 2) on coronary pressure-flow autoregulation, and 3) on recovery -of stunned myocardium. In addition, the role of the vascular endothelium will be investigated by observing the effects of inhibiting synthesis of endothelium derived relaxing factor (EDRF) with N-G-monomethyl-L-arginine (L-NMMA) and of damaging the endothelium by occlusion followed by reperfusion on anesthetic-induced vasodilator responses. Finally, time-dependent recovery of coronary vascular tone during prolonged exposure to the volatile anesthetics, i.e. , vascular adaptation, will be assessed. The proposed study will provide new, fundamental, pharmacologic data concerning direct effects of the volatile anesthetics in the myocardium. It will also provide information on the efficacy of the volatile anesthetics in accelerating post-ischemic functional recovery of stunned myocardium. Findings from the study will provide insight into which of the volatile anesthetics is most suitable for use in patients with known or suspected coronary artery disease and in patients undergoing surgery for coronary revascularization.
