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This study tests the hypothesis that irreversible muscle damage does not occur after as long as 6 hours of ischemia before reperfusion, immediate functional recovery is possible by controlling the conditions of reperfusion during total vented bypass and the composition of the reperfusate with substrate-enriched blood cardioplegic solution, and such control can be accomplished without thoracotomy. Of 43 dogs undergoing 2 to 6 hours of left anterior descending coronary occlusion, seven were studied by ultrastructural and mitochondrial analyses after 6 hours of regional coronary occlusion without reperfusion. Sixteen other dogs were reperfused with normal blood, with the heart in the beating state after 2 to 4 hours of ischemia, and 20 dogs received regional substrate-enriched blood cardioplegic reperfusion after 2 to 6 hours of ischemia for 20 minutes during total vented bypass accomplished through the femoral artery, femoral vein, and transaortic left ventricular venting. Six hours of ischemia without reperfusion caused minimal changes in mitochondrial structure and retained mitochondrial adenosine triphosphate production capacity at 64% of control values despite complete depletion of tissue adenosine triphosphate. Reperfusion with normal blood in the beating, working hearts caused extensive structural damage, reduced reflow, and failed to restore contractility in any instance (-27% systolic shortening, p less than 0.05). In contrast, regional cardioplegic reperfusion during total vented bypass at 2, 4, and 6 hours caused 52 +/- 3%, 41 +/- 7%, and 21 +/- 6% immediate recovery of regional contractile function. The seven hearts reperfused at 6 hours of ischemia had more segmental shortening (21% versus -27%, p less than 0.05), less edema (81% versus 83% water content, p less than 0.05), and more postischemic flow (57 versus 18 ml/100 gm/min in subendocardial muscle, p less than 0.05) than did 2-hour controls, and postischemic ultrastructure was not altered by reperfusion. Six hours of ischemia does not produce irreversible damage, and immediate recovery of contractile function is possible if the conditions of reperfusion are controlled with total vented bypass and a regional substrate-enriched blood cardioplegic solution is administered. Such control can be obtained by the peripheral cannulation technique.

This study applies the low protein-denaturation embedding technique for mitochondrial preparation to analyze control cardiac tissue, heart muscle subjected to 6 hours of regional ischemia without reperfusion, and myocardial tissue subjected to 4 to 6 hours of ischemia followed by reperfusion either with normal blood, with the heart in the beating, working state, or with substrate-enriched blood cardioplegia during total vented bypass. Parallel specimens of cardiac tissue were analyzed for ultrastructure by the conventional osmium tetroxide fixation method. Results following conventional tissue preparation with osmium tetroxide showed extensive ultrastructural damage in all hearts subjected to ischemia, with no correlation between ultrastructural findings and methods of reperfusion or functional recovery. In contrast, results following tissue preparation by the low protein-denaturation method showed reperfusion with normal blood in working hearts to cause severe mitochondrial damage, cardiac mitochondria that were intact structurally after 6 hours of ischemia and after controlled reperfusion, a logical sequence of mitochondrial structural changes that may lead to irreversibility, and a new method of quantification of such changes.