The Effects of Insulin on Myocardial Glucose Metabolism and Contractile Function During Moderate Coronary Hypoperfusion

Tune, Jonathan David, The Effects on Insulin on Myocardial Glucose Metabolism and Contractile Function during Moderate Coronary Hypoperfusion Doctor of Philosophy (Biomedical Sciences), August, 1997, 98 pp, 3 tables, 11 figures, references, 117 titles. This study was designed to determine the effects of insulin on myocardial metabolism and contractile function during moderate coronary hypoperfusion. Coronary perfusion pressure (CPP) was lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery of anesthetized, open chest dogs. Regional glucose uptake, lactate uptake, oxygen consumption (MVO2), and percent segment shortening were determined without (n=12) or with either intravenous insulin (4 U/min, n=12) or intracoronary insulin (4 U/min, n=6). Glucose metabolites, high energy phosphates, and the phosphorylation state of creatine phosphate were determine in freeze clamped biopsies of control (n=6), and of intravenous insulin (n=6) treated hearts at the completion of the protocol (CPP = 40 mmHg). Glucose uptake increased with both intravenous and intracoronary insulin treatments (P0.05). Thus, insulin treatment improved contractile function while myocardial oxygen demand was unchanged, i.e. oxygen utilization efficiency increased. Myocardial glycogen, alanine, lactate, and pyruvate contents were not significantly different in untreated and intravenous insulin treated hearts. Reducing CPP to 40 mmHg produced similar changes in both untreated and insulin treated hearts: ATP content was unchanged, creatine phosphate content decreased 17%, creatine content and inorganic phosphate concentration increased 27% and 124%, respectively, and the phosphorylation potential decreased 80%. We conclude that 1) when the potentially detrimental effects on insulin stimulated glucose metabolism are avoided during moderate ischemia, insulin treatment increases contractile function without significantly elevating myocardial oxygen demand; 2) during moderate ischemia, insulin stimulated glucose metabolism increases oxygen utilization efficiency and prevents a further decline in the energy state of the myocardium.