MYOCARDIAL PROTECTION BY NA-H+ EXCHANGE INHIBITION IN ISCHEMIC, REPERFUSED PORCINE HEARTS()

Background Studies in isolated myocytes and isolated heart preparation s have suggested that Na+-H+ exchange is an important mechanism for my ocardial ischemia-reperfusion injury. This study was undertaken to det ermine whether inhibition of Na+-H+ exchange limits infarct size and i mproves regional systolic shortening in regional ischemia and reperfus ion in intact pigs. Methods and Results The left anterior descending c oronary artery was occluded in 18 anesthetized and thoracotomized pigs for 45 minutes and then reperfused for 24 hours. As main end points o f this study, regional systolic shortening (sonomicrometry) and infarc t size (percentage of infarcted to ischemic myocardium) were determine d at the end of the experiments. Infarcted myocardium was assessed by histochemistry (tetrazolium stain) and by quantitative histology of on e heart slice. The Na+-H+ exchange inhibitor Hoe 694 was administered intravenously at a dose of 3 mg/kg in 6 pigs each either 10 minutes be fore ischemia (group A) or 10 minutes before the onset of reperfusion (group B). Six pigs served as controls (group C). Treatment with Hoe 6 94 before ischemia decreased histochemical infarct size from 65+/-18% (control group) to 13+/-8% (P<.01) and histological infarct size from 49+/-20% (control group) to 14+/-4% (P<.01). Histochemical (55+/-19%) and histological (42+/-15%) infarct sizes of group B were insignifican tly reduced by 15%. Myocardial protection in group A was associated wi th an attenuated contracture after 10 minutes of reperfusion and an im proved regional systolic shortening after 24 hours of reperfusion (gro up A, 25+/-12%; control group, 6+/-5%; P=.01). These parameters remain ed unaffected in group B. Conclusions This study clearly demonstrates that Na+-H+ exchange is an important mechanism for cell death in myoca rdial ischemia and reperfusion in intact pigs; thus, inhibition of thi s exchange system may prove a promising new strategy in the clinical t reatment of myocardial ischemia and reperfusion.