Inhibition of Na(+)/H(+) isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage.

Objectives: Cardiac ischemia-reperfusion activates Na+/H+ exchange; excess Na+ and the resulting Ca2+ overload, through reverse Na+/Ca2+ exchange, cause cellular injury and cardiac dysfunction. We postulated that inhibiting the Na+/H+ isoform-1 exchanger Would add to the protection of hearts after long-term cold storage in acidic cardioplegic solution. Methods: Guinea pig hearts were isolated and perfused at 37degreesC with Krebs-Ringer's solution (KRS) and then switched to an acidic St. Thomas solution (STS) at 25degreesC. Perfusion was stopped at 10degreesC, and hearts were stored for 6 hours in STS at 3.4degreesC. On reperfusion to 25degreesC, hearts were perfused with KRS for 60 minutes. Hearts were divided into 4 groups: sham control (SHAM); emporide (EPR, EMD96785) IV, 1 mg/kg given IV over 15 minutes before heart isolation; EPR intracoronary, 1 mumol/liter in STS given intracoronary after heart isolation: and EPR IV and intracoronary. Results: Values at 60 minutes reperfusion (the percentage of control [100%] before cold storage) are given, respectively, for EPR IV. EPR intracoronary, and EPR IV and intracoronary vs drug-free SHAM (SEM, *p < 0.05 vs SHAM): 72% +/- 3%*, 65% +/- 3%,*, and 81%, +/- 2%* vs 55% +/- 3% for left ventricular pressure; 94% +/- 3%*, 96% +/- 5%*, and 102% +/- 2%* vs 81% +/- 3% for coronary flow, 60% +/- 2%, 58% +/- 3%, and 74%,* 3% vs, 58% +/- 4% for cardiac efficiency; 106% +/- 2%*, 108% +/- 3%*, and 107% +/- 2%* vs 116% +/- 4% for percentage of O-2 extraction. Infarct size as percentage of ventricular weight was 20% +/- 3%*, 31% +/- 3%, and 6% +/- 2%* vs 35% +/- 3% (SHAM) after 60 minutes of reperfusion. Conclusions: Na+/H+ isoform-1 exchanger inhibition, particularly if given IV before storage and intracoronary during cooling and rewarming, adds to the protection of cardioplegic solutions.