Time-dependent Protection by Na+/H+Exchange Inhibition in a Regionally Ischemic, Reperfused Porcine Heart Preparation with Low Residual Blood Flow

Abstract

Inhibition of Na+/H+ exchange has been shown to protect the ischemic reperfused myocardium. This study investigated the time-dependent beneficial effect of the Na+/H+ exchange inhibitor HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanedine methanesulphonite, cariporide). The left anterior descending coronary artery was ligated in 21 pigs (seven control animals) for 60 min and then reperfused for 24 h. An extracorporeal bypass system was used to achieve a constant residual blood flow of 3 ml/min within the ischemic myocardium. Cariporide (1 mg/kg) was injected intravenously in seven pigs after 15 min of ischemia (group A), and in another seven animals after 45 min of ischemia (group B). Histochemical (tetrazolium stain) and histologic infarct sizes were determined at the end of the experiments. Regional systolic shortening was determined by sonomicrometry. Mean calculated residual blood flows (ml/min/g of ischemic myocardium) amounted to 0.106 (group A), 0.093 (group B), and 0.117 (control group). Histochemical (32.9 +/- 21%) and histologic infarct sizes (36.7 +/- 17.7%) were significantly reduced in group A compared to both the control group (histochemical infarct size, 62.5 +/- 16.1%, P < 0.01; histologic infarct size. 67.8 +/- 16.3%, P = 0.013) and group B (histochemical infarct size 64.8 +/- 12.2%, P < 0.01; histologic infarct size 67.1 +/- 15.6%, P < 0.01). Infarct sizes of group B did not differ from control values. Recovery of regional systolic shortening after 24 h of reperfusion was insignificantly improved in group A compared to both other groups. In conclusion, inhibition of Na+/H+ exchange during early ischemia reduced cell death in an ischemic reperfused preparation with low residual blood flow.