Anesthetics are general metabolic and functional depressants, and this organ depression can often be reliably and reversibly controlled. The overall objective of the proposed research is to continue to investigate the concept that deliberate anesthetic-induced metabolic depression can provide protection to various organs during regional or global ischemia. Barbiturate cerebral protection against regional ischemia is now generally accepted to occur in animals, but no clear human evidence exists. The major thrust of our work is in the area of anesthetic-induced cardiac depression as protection against global or regional myocardial ischemia. We have already shown that there are sharp qualitative differences between anesthetics in this regard, with implications as to clinical choice of anesthesia for patients with coronary artery disease. Our studies thus far have indicated that barbiturates may in fact be deleterious to ischemic myocardium, relative to volatile anesthesia, just the opposite of their cerebral effects. This has important clinical implications, because barbiturates are being administered to patients following resuscitation after cardiac arrest. Often, of course, that cardiac arrest was due to myocardial infarction. We have devised a number of distinctly different approaches to examine the possibility that anesthetics might be myocardial protectants. These include high energy phosphate depletion studies; left ventricular regional wall motion studies; studies of return of left ventricular function after global ischemia; studies of coronary blood flow effects of dysrhythmias and anesthetics; and studies in patients of protection against post-bypass hypothermia by vasodilation during rewarming. Further, we propose "intensive care" animal studies of myocardial infarct size vs. deliberate 48 hour deep general anesthesia. We are excited by the possibility that anesthetics might prove therapeutic, but even if not, we need to provide objective cardiac reasons for choosing anesthesia for patients with potentially ischemic heart disease, by providing evidence regarding specific effects of anesthetics on ischemic myocardium.