ACIDEMIA AND HYPERNATREMIA ENHANCE POSTISCHEMIC RECOVERY OF EXCITATION-CONTRACTION COUPLING

The purpose of the present study was to determine whether Na+-H+ and N a+-Ca2+ exchanges modulate postischemic recovery of excitation-contrac tion coupling. Experiments were performed in 43 isolated isovolumic do g hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, p aced at 2 Hz). A 3x3-mm region at the left ventricular (LV) apex was l oaded with aequorin for monitoring [Ca2+](i) simultaneously with LV pr essure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na +, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic bl ood (141 mmol/L Na++30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediate ly followed by an increase in [Ca2+](i) and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or belo w baseline. Ventricular arrhythmia occurred during this period (>80%). This transient increase of [Ca2+](i) was attenuated by acidemic or hy pernatremic perfusate. With acidemic or hypernatremic reperfusion, rec overy of LV developed pressure at 20 minutes was more complete than wi th unmodified control reperfusion: acidemic blood (n=7), 93-/+3% (P<.0 1); hypernatremic blood (149 mmol/L Na+, n=7), 89+/-2% (P<.02); hypern atremic blood (157 mmol/L Na+, n=4), 91+/-2% (P<.01); and unmodified c ontrol blood (n=17), 80+/-2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82+/-3%). Fro m these results we conclude that (1) an increase in intracellular Ca2 occurs transiently after no-flow ischemia and may cause arrhythmia an d decreased Ca2+ responsiveness of the contractile elements, (2) acide mic and hypernatremic reperfusion ameliorates postischemic dysfunction by preventing the increase in intracellular Ca2+, suggesting that (3) Na+-H+ and Na+-Ca2+ exchange may play important modulatory roles duri ng reperfusion.