This proposal will test the hypothesis that temporary extracorporeal circulatory assistance (TECA) can accelerate recovery of left ventricular function, reduce infarct size, and thereby improve survival by reducing circumferential and regional myocardial wall stresses after acute myocardial infarction (AMI) with or without reperfusion of the obstructed coronary artery. Centrifugal pump perfusion systems will be modified for use in AMI by developing techniques for peripheral, percutaneous cannulation, cannulation of the left atrium without thoracotomy, pulsatile perfusion, and perfusion with low dose or no heparin. Seven perfusion system combinations, suitable for use in AMI, will then be evaluated for their ability to reduce left ventricular wall stress in poorly contractile, pentobarbital-suppressed sheep hearts. Left atrial-to-femoral artery and veno-arterial bypass systems with both continuous and timed pulsatile flow with and without intra-aortic balloon counterpulsation will be studied. One system, which maximally reduces left ventricular wall stress and which is most practical for use in AMI, will be chosen for AMI studies. The ability of TECA to accelerate recovery of well-perfused, poorly contractile ventricular segments and to reduce infarct size will be evaluated in sheep with occlusion of the circumflex coronary artery. Myocardial regional wall shortening, wall thickness and short and long axis diameters will be measured by sonomicrometry in addition to aortic flow and cardiac chamber pressures. Awake sheep will be perfused for 96 hours using the chosen TECA system and compared to unperfused control animals. Calculated estimates of regional wall stresses will be made, and after euthanasia, size of the infarcted area will be determined. The effects of reperfusion of reversibly and irreversibly ischemic myocardium on regional wall motion, calculated estimates of regional wall stress, and overall ventricular function with and without TECA will be determined in the sheep model of circumflex coronary artery occlusion. The data obtained will define the role, if any, of TECA in AMI and will quantitate changes in regional wall motion, calculated estimates of regional wall stress, and overall ventricular performance after no, early, and late reperfusion of an obstructed coronary artery. This information may influence current management of patients with large acute myocardial infarctions.
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