Na+/H+ exchange inhibitor cariporide attenuates cell injury predominantly during ischemia and not at onset of reperfusion in porcine hearts with low residual blood flow

Background-This study investigated whether myocardial protection by inhibition of Na+/H+ exchange (NHE) occurs during ischemia and/or during reperfusion. Methods and Results-The left anterior descending coronary artery was occluded in 32 pigs for 60 minutes and then reperfused for 24 hours. Infarct sizes (nitroblue tetrazolium [NBT] stain, histology) were determined at the end of the experiments. An extracorporeal bypass was used to achieve a constant residual blood flow of 3 mL/min in the myocardium at risk during ischemia. The NHE-1 inhibitor cariporide or distilled water was infused into the extracorporeal bypass system. In group 1, active treatment was administered from the onset of ischemia until 10 minutes of reperfusion (n = 8). In group 2, active treatment was infused during the first 30 minutes of ischemia only (n = 8). The group 3 animals (n = 8) received intracoronary cariporide after 45 minutes of ischemia until 10 minutes of reperfusion. The control animals (group 4, n = 7) were treated similarly to group I animals, with the cariporide solution being replaced by distilled water. Infarct sizes of group 1 (NBT stain, 41.5+/-20%; histology, 44.6+/-12%) and group 2 (NBT stain, 33.5+/-14%; histology 34.9+/-15%) differed significantly (at least P = 0.012) from infarct sizes of group 3 (NBT stain, 71.6+/-15%; histology, 69.2+/-12%) and the control group (NBT stain, 76+/-9%; histology 72.4+/-12%). Cariporide treatment in group 1 and group 2 significantly improved functional recovery after 24 hours of reperfusion. Conclusions-Myocardial protection by cariporide is predominantly achieved by NHE inhibition during ischemia and not during early reperfusion.