INSULIN IMPROVES CARDIAC CONTRACTILE FUNCTION AND OXYGEN UTILIZATION EFFICIENCY DURING MODERATE ISCHEMIA WITHOUT COMPROMISING MYOCARDIAL ENERGETICS

Insulin improves myocardial contractile function during moderate ische mia, but the mechanism is unknown. To determine effects of insulin on myocardial oxygen utilization efficiency (O2UE) and energetics, region al left coronary perfusion pressure (CPP) was lowered sequentially fro m 100 to 60, 50, and 40 mmHg in 24 anesthetized, open-chest dogs. Regi onal power index (PI), myocardial oxygen consumption (MVO2), and O2UE index (PI/MVO2) were determined in untreated and insulin treated (4 U/ min, i.v.) hearts. Biopsies were obtained from six untreated and six i nsulin-treated hearts at CPP = 40 mmHg for determining high energy pho sphates and the cytosolic phosphorylation potential. Measurements were compared with data from normal, untreated myocardium (n = 11). MVO2 f ell (P < 0.05) in all hearts as CPP was lowered to 40 mmHg, and was un affected by insulin treatment. PI decreased 32 and 75% in untreated he arts at CPP = 50 and 40 mmHg, respectively (P < 0.05). In insulin trea ted hearts, PI was not significantly depressed at CPP > 40 mmHg, and f ell only 26% at CPP = 40 mmHg. O2UE increased (P < 0.05) in all hearts at CPP = 60 mmHg. In insulin treated hearts, O2UE was greater (P < 0. 05) at CPP = 50 and 40 mmHg than at CPP = 100 mmHg, and greater (P<0.0 5) than in untreated hearts at CPP = 40 mmHg. Reducing CPP to 40 mmHg produced similar metabolic changes in all hearts. Compared to normal m yocardium, ATP content of untreated and treated hearts was unchanged, creatine phosphate content decreased 21 and 14%, creatine content incr eased 24 and 30%, inorganic phosphate concentration increased 108 and 140%, and phosphorylation potential decreased 80 and 77%. We conclude that insulin markedly improves PI and O2UE without altering cytosolic energetics during moderate myocardial ischemia. (C) 1998 Academic Pres s.