The role of glucose metabolism in a pig heart model of short-term hibernation

Previously, we reported, alterations in glucose metabolism in a 4 day model of chronic coronary stenosis similar to those described in patients with hibernating hearts. The purpose of this study was 2 fold: (1) to identify whether an acute model of mild, sustained ischemia could effect similar changes, and (2) to determine the effects of pharmacological inhibition of glycolysis. In the first group, extracorporeally perfused, intact pig hearts were subjected to 85 min of a 40% reduction in left anterior descending (LAD) coronary arterial blood flow. A second group was subjected to the same protocol, except after 40 min of LAD regional ischemia, iodoacetate (IAA) was administered to block glycolysis. Ischemia reduced MVO₂ by 10% in both groups with a further 20% reduction noted following IAA treatment. Regional systolic shortening was reduced nearly 50% by ischemia and decreased an additional 40% following treatment with IAA. Glycolysis was increased by over 700% with ischemia in the first group. IAA caused a 3 fold reduction in glycolysis as compared to the preceding ischemic period and inhibited lactate production. Fatty acid metabolism was significantly reduced by ischemia in the first group, but was not reduced in the IAA group. Activity of creatine kinase associated with myofibrils was reduced and may have contributed to the contractile dysfunction. In conclusion, this acute model of short-term hibernation demonstrates several metabolic changes previously reported in chronic hibernation and may prove useful in determining mechanisms of substrate utilization in simulated conditions of chronic coronary stenosis and hibernation.