Seventy percent of the approximately one million Americans who suffer myocardial infarction (MI) each year die as a result. The chief cause of death is left ventricular failure which is directly proportional to the size of the MI. An effective means of limiting MI size is reducing the amount of work required of the infarcted LV and thus lowering myocardial oxygen demand to the point where it might be met by the existing collateral circulation. Left heart bypass, especially left atrium-femoral artery (LA/FA) bypass, provides such a means of reducing myocardial work. Using dye markers to measure the area of infarct in the LV as a percentage of the LV area at risk, we have been able to show in open-chest dogs that after ligation of the left anterior descending coronary artery, the prompt use of LA/FA bypass over a 4 hour period significantly reduces the area of infarct at the end of this period as a percentage of the LV area at risk by as much as 50 percent. We have further shown that the addition of synchronized counterpulsation to LA/FA bypass (PLA/FA) results in significantly more effective limitation of MI size than non-pulsatile LA/FA bypass. The present proposal seeks to use this open-chest PLA/FA bypass model and similar methods to extend these promising findings in order to learn: 1) the maximum post-MI period after which PLA/FA bypass is still effective in significantly reducing MI size; 2) problems associated with weaning off PLA/FA bypass and whether MI expansion resumes after weaning; and 3) whether PLA/FA bypass limitation of MI expansion can make less than immediate revascularization of the MI an effective aid in permanently limiting MI size. Dye marker delineations of areas of infarct and areas at risk will be confirmed by direct ultrastructural examination. Edema, regional blood flow changes, tension time index changes, mortality, etc. will also be measured and statistically compared. Based on this information, we will then test whether a safer, more clinically useful closed-chest dog model of PLA/FA bypass can similarly significantly reduce MI size. The data provided by all of these experiments should form the basis for clinical trials of closed-chest, percutaneous PLA/FA bypass as an effective therapy for limiting infarct expansion and LV failure after acute MI.
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