Insulin improves cardiac contractile function without further decline in energetics during moderate ischemia

Abstract

We determined if insulin induced increases in cardiac contractile function occur at the expense of myocardial high energy phosphates and cytosolic energetics during moderate coronary hypoperfusion. Regional segment shortening (SS) was measured as perfusion pressure (CPP) was lowered from 100 mmHg (control) to 60, 50, and 40 mmHg for 30 min intervals in the left anterior descending coronary artery of 12 anesthetized, open chest dogs. Regional myocardial biopsies were obtained at CPP = 40 mmHg in untreated (n=6) and in intravenous insulin (4 U/min, n=6) treated hearts for determination of high energy phosphates (μmol/g dry), intracellular inorganic phosphate (Pi) concentration (mM), and the phosphorylation state (PP) of creatine phosphate (CrP), i.e. [CrP]/[creatine][Pi](M-1). Energy metabolites were also measured in untreated myocardium at CPP = 100 mmHg (n=11). Without insulin, SS fell 72% (7<0.05) at CPP = 40 mmHg, but was not reduced (P>0.05) in insulin treated hearts. Reducing CPP to 40 mmHg produced similar energetic changes in both untreated and insulin treated myocardium (mean±SE; *= P0.05): CPP (mmHg) ATP Crp Pi PP 100: Untreated 21.3±2 52.9±2 5.6±1 271±53 40: Untreated 22.9±2 41.8±4* 11.7±1* 55±7* 40: Insulin Treated 23.1±1 45.7±1* 13.4±1* 61±9* Conclusion: During moderate ischemia, insulin improves cardiac contractile function without provoking a further decline in myocardial energy state.

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