ACIDEMIA AND HYPERNATREMIA ENHANCE POSTISCHEMIC RECOVERY OF EXCITATION-CONTRACTION COUPLING

The purpose of the present study was to determine whether Na+-H+ and Na+-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3x3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+](i) simultaneously with LV pressure. 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 blood (141 mmol/L Na++30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+](i) and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or below baseline. Ventricular arrhythmia occurred during this period (>80%). This transient increase of [Ca2+](i) was attenuated by acidemic or hypernatremic perfusate. With acidemic or hypernatremic reperfusion, recovery of LV developed pressure at 20 minutes was more complete than with unmodified control reperfusion: acidemic blood (n=7), 93-/+3% (P<.01); hypernatremic blood (149 mmol/L Na+, n=7), 89+/-2% (P<.02); hypernatremic blood (157 mmol/L Na+, n=4), 91+/-2% (P<.01); and unmodified control blood (n=17), 80+/-2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82+/-3%). From these results we conclude that (1) an increase in intracellular Ca2+ occurs transiently after no-flow ischemia and may cause arrhythmia and decreased Ca2+ responsiveness of the contractile elements, (2) acidemic 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 during reperfusion.