Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia

Background. Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity du ring ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection affor ded by K/Mg cardioplegia was unknown. Methods. Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minu tes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts r eceived cardioplegia 5 minutes before ischemia. Separate groups of GI and K /Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642- I), at the immediate start of reperfusion (HOE-642-R), or both before ische mia and at the immediate start of reperfusion (HOE-642-IR). Results. Left ventricular peak developed pressure was significantly increas ed in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all group s, but was significantly increased in HOE-R as compared with HOE-IR (p <les s than> 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decrea sed left ventricular peak developed pressure after 90 minutes of reperfusio n (p < 0.05 versus K/Mg), with no significant effect on infarct size. Conclusions. NHE-1 inhibition used alone provides cardioprotection with opt imal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardiop legia decreases postischemic functional recovery during late reperfusion. < (c)> 2001 by The Society of Thoracic Surgeons.