Metabolic substrates can alter postischemic recovery in preconditioned ischemic heart

T. A. Fralix, C. Steenbergen, R. E. London and E. Murphy Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park 27709. The mechanisms that contribute to myocardial cell injury are not well understood. Furthermore, the ability of reperfusion conditions to modify ischemic injury is unclear. Recent studies have indicated that glucose utilization may improve ionic homeostasis. Because considerable derangement of ion concentrations occurs during ischemia, glucose utilization may be beneficial when stimulated during the reperfusion period. The effects of glycolytic vs. mitochondrial substrates on postischemic contractile function, high-energy phosphates and ion balance (intracellular Ca2+ and pH) were determined. Reperfusion conditions were compared in the "preconditioned ischemic" heart where baseline contractile recovery during reperfusion with glucose as the sole exogenous substrate was 74 +/- 5% (n = 10). Contractile recovery was determined for reperfusion with pyruvate (14 +/- 2%, n = 10), pyruvate+glucose (23 +/- 4%, n = 10), deoxyglucose+acetate (25 +/- 4%, n = 10), and lactate+glucose (60 +/- 11%, n = 10). Contractile dysfunction could not be attributed to differences in high-energy phosphate contents. Elevated levels of intracellular Ca2+ during reperfusion were, however, correlated with poor contractile function. After 20 min of reperfusion, the mean time-averaged intracellular Ca2+ values, measured with 19F-nuclear magnetic resonance of 5-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded hearts, were 994 +/- 110 nM (glucose, n = 5), 2,270 +/- 494 nM (pyruvate, n = 5), 2,671 +/- 419 nM (pyruvate+glucose, n = 5), 2,382 +/- 480 nM (deoxyglucose+acetate, n = 5), and 1,019 +/- 33 nM (lactate+glucose, n = 5). These results are consistent with a beneficial role for glucose utilization during reperfusion, where enhanced recovery of contractile function and ionic homeostasis were observed.