MYOCARDIAL-METABOLISM IN CHRONIC REPERFUSION AFTER NONTRANSMURAL INFARCTION IN PIG HEARTS

The purpose of these studies was to evaluate metabolic behavior in a 4 -day reperfusion model in pigs after induction of subendocardial infar ction. Two groups of swine [sham and intervention (Int) groups, n = 7 and 10 hearts per group, respectively] were prepared comparably with t wo surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descendi ng (LAD) circulation was partially restricted (by 60 %) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 +/- 0.2 ml . min-1 . g dry wt-1) for 60 min and infused by equilibrium labeli ng with [U-C-14]palmitate and [5-H-3]glucose to estimate fatty acid ox idation and exogenous glucose utilization. During extracorporeal perfu sion, regional myocardial shortening and oxygen consumption were compa rable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a signific ant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by (CO2)-C-14 production was 34.00 +/- 4.72 mumol . h-1 . g dry wt-1 (av eraged from 30-60 min of perfusion) in sham hearts but was decreased ( by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utiliza tion may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltran sferase. Reduction in fatty acid oxidation in Int hearts was attended by a modest rise (P < 0.013 compared with sham hearts) in exogenous gl ucose utilization but no net lactate production. These studies indicat ed that after subendocardial injury, mitochondrial respiration is depr essed in remaining viable myocardium and is accompanied by altered met abolism with decreased rates of fatty acid utilization and oxidation a nd increased rates of glucose utilization. However, despite the eviden ce for mitochondrial dysfunction, mechanical recovery was near complet e, and metabolic performance remained predominantly aerobic with near normal levels of myocardial oxygen consumption and no evidence for inc reased anaerobic glycolysis.