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

Abstract

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 1 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.