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 mechanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood. Methods. Sodium-propionate–induced cell swelling, an indicator of the function of the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Langendorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recovery of cardiac function after hypothermic ischemia. This was done using FR168888, an inhibitor of Na+/H+ exchange. Results. In the in vitro study, rat lymphocytes were observed to swell at 17°, 22°, and 27°C, indicating that the Na+/H+ exchanger remains functional even under hypothermic conditions. FR168888 was found to significantly inhibit Na+/H+ exchange–induced cell swelling, even at 17°C. In the in vivo study, pretreatment with FR168888 was found to prevent the deterioration of ventricular function, even after 5 hours of 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 injury, even after hypothermic cardioplegic arrest.