The long-term objective is to evolve a new approach to acute myocardial infarction (AMI) to reduce substantially the disappointing 10-I5% CCU mortality resulting from current medical treatment. Hypothesis: The fate of ischemic myocardium is determined by the conditions under which blood supply is restored (reperfusion) rather than how quickly it is re-established. Methods: Using a dog model of acute coronary occlusion, the structural, functional, metabolic consequences of cardiac damage which can be avoided by controlling re-perfu-sate conditions (i.e., pressure, f)ow, LV venting) and composition (i.e., substrates, 02 radicals) will be characterized. These studies will: a. show all AMI patients can be helped by controlled reperfusion, even after time intervals thought previously to produce irreversible damage (> 6 hrs). b. demonstrate that controlled reperfusion (i.e., blood cardioplegia on total bypass) can be delivered in the cath lab or operating room and produce immediate recovery of contractility in jeopardized muscle. c. present a new method of instituting percutaneous total vented bypass and regional reperfusion without thoracotomy that is applicable in the catheterization lab. d. show that complications of AMI (i.e., intractable fibrillation, shock extension) are due to previously unrecognized problems in remote (non-ischemic) muscle that can be treated successfully by directing medical and surgical efforts towards remote rather than infarcting muscle. e. develop a new """"""""intravenous IV substrate infusion"""""""" to treat cariogenic shock and postoperative low output which corrects specific metabolic deficiencies that cause myocardial dysfunction, and limits inotropic drug requirements. f. apply reperfusion principles to allow: a) safe cardiac surgery in energy-depleted hearts (i.e., ischemia, hypoxia, hypertrophy) and b) storage for prolonged intervals (48-72 hours) and permit organ bank development for transplantation.
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