NMR measurements of Na+ and cellular energy in ischemic rat heart: role of Na(+)-H+ exchange

M. M. Pike, C. S. Luo, M. D. Clark, K. A. Kirk, M. Kitakaze, M. C. Madden, E. J. Cragoe Jr and G. M. Pohost Department of Medicine, University of Alabama at Birmingham 35294. Interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectra were continuously collected on perfused rat hearts subjected to low-flow ischemia (30 min, 10% flow) or zero-flow ischemia (21 min) followed by reperfusion. During untreated low-flow and zero-flow ischemia, intracellular Na+ (Nai+) increased by 53 +/- 11 (+/- SE) and 78 +/- 8%, respectively, and remained elevated for zero-flow hearts. However, during both low- and zero-flow ischemia, Nai+ did not increase in hearts treated with the Na(+)-H+ exchange inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). The pH decreases during ischemia were unchanged. EIPA treatment reduced ATP depletion during ischemia. During reperfusion from zero-flow ischemia, EIPA-treated hearts displayed more rapid and extensive recoveries of phosphocreatine and ATP. Recovery of left ventricular developed pressure was improved for zero-flow hearts treated with EIPA during the ischemic period exclusively (104 +/- 13%) compared with untreated hearts (36 +/- 21%). These data indicate that Na(+)-H+ exchange is an important mechanism for Nai+ accumulation, but not for pH regulation, during myocardial ischemia. Additionally, Nai+ homeostasis plays an important role in the postischemic recovery of cellular energy and ventricular function.