Energy metabolism, intracellular Na+ and contractile function in isolated pig and rat hearts during cardioplegic ischemia and reperfusion: 23Na- and 31P-NMR studies.

The purpose of the study was to compare the role of Na ions in the damage caused by cardioplegic ischemia in fast (rat) and slow (pig) hearts. Changes in intracellular Na+ (Na+i), high energy phosphates, and contractile function were assessed during ischemia (36 degrees C) and reperfusion in KCl-arrested perfused hearts using 31P-NMR and shift reagent (DyTTHA3-)-aided 23Na-NMR spectroscopy. In the pig hearts the rates of decrease of phosphocreatine (PCr), ATP and intracellular pH (pHi) were 3-4 times slower than the rates observed in the rat hearts. In the pig hearts PCr was observable (approximately 10%) during first 80 min of the ischemic period (90 min). Comparable decreases in ATP (32.0 +/- 6 vs. 38 +/- 15% of initial) and pHi, (to 6.14 +/- 0.06 vs. 6.10 +/- 0.15) observed after 90 and 20 min ischemia in pig and rat hearts, respectively, were associated with a smaller Na+i increase in the pig hearts (to 175 +/- 31%) than in the rat hearts (to 368 +/- 62%). This Na+ increase in the rat hearts preceded development of ischemic contracture (41 +/- 6 mmHg at 23.6 +/- 0.7 min) while no contracture was observed in pig hearts. Reperfusion of the rat hearts (at 30 min ischemia) was followed by partial recovery of PCr (44 +/- 3%) and Na+i (234 +/- 69%) and poorer recovery of the pressure-rate product (PRP, 9 +/- 4%) and end-diastolic pressure (EDP, 72 +/- 5 mmHg) compared to the pig hearts (PCr, 106 +/- 25%; Na+i, 82 +/- 17%; PRP, 24 +/- 3%; EDP, 4.6 +/- 2.5 mmHg). The loss of function in the pig hearts was reversed by increasing Ca++ in the perfusate from 1 to 2.3 mM and resulted in a rise in both PRP and oxygen consumption rate, V(O2), from 24 +/- 3.3 to 64.5 +/- 5.8% and from 55 +/- 10 to 74 +/- 10% of the control levels, respectively. The PRP/delta V(O2) ratio was halved in the post-ischemic pig hearts and returned to the pre-ischemic level following Ca++ stimulation. It is suggested that the higher stability of Na+ homeostasis to ischemic stress in the pig heart may result from: 1) a lower ratio of the rate of ATP hydrolysis to glycolytic ATP production; 2) differences in the kinetic properties of the Na+ transporters. Reduced Na+ accumulation during ischemia and reperfusion is beneficial for metabolic and functional preservation of cardiomyocytes.