THE CONTRIBUTION OF NA+ H+ EXCHANGE TO ISCHEMIA-REPERFUSION INJURY AFTER HYPOTHERMIC CARDIOPLEGIC ARREST/

Background. Na+/H+ exchange has been reported to be one of the key mec hanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood. Methods. S odium-propionate-induced cell swelling; an indicator of the function o f the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Lang endorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recov ery of cardiac function after hypothermic ischemia. This was done usin g FR168888, an inhibitor of Na+/H+ exchange. Results. In the in vitro study, rat lymphocytes were observed to swell at 17 degrees, 22 degree s, and 27 degrees C, indicating that the Na+/H+ exchanger remains func tional even under hypothermic conditions. FR168888 was found to signif icantly inhibit Na+/H+ exchange-induced cell swelling, even at 17 degr ees C. In the in vivo study, pretreatment with FR168888 was found to p revent the deterioration of ventricular function, even after 5 hours o f hypothermic cardioplegic arrest. This was associated with a decrease in the reperfusion-induced elevation in resting tension. Conclusions. These results suggest that Na+/H+ exchange in the heart still occurs, even under hypothermic conditions, and contributes to reperfusion inj ury, even after hypothermic cardioplegic arrest. (C) 1997 by The Socie ty of Thoracic Surgeons.