Cardioprotection with cariporide, a sodium-proton exchanger inhibitor, after prolonged ischemia and reperfusion in senescent rats.

This study investigated the effects of cariporide, an inhibitor of sodium-proton exchanger (NHE), during myocardial ischemia and reperfusion in senescence. Isolated Langendorff perfused hearts from 4 (adult) and 24 (senescent) month old male Wistar rats were submitted to prolonged low-flow ischemia (LFI) at 15% of initial coronary flow (180 min) or to 45 min of LFI (15% of initial coronary flow) followed by 30 min of reperfusion, without or with cariporide (10(-6)M). In senescent hearts, but not in adults, treatment with cariporide during prolonged LFI attenuated the elevation of coronary resistances (578 +/- 84 vs 1020 +/- 129% of baseline value after 180 min, P < 0.05) and delayed the decrease in active tension (35.6 +/- 5.1 vs 22.2 +/- 3.4% of baseline value after 60 min; P < 0.05). During reperfusion following LFI, the coronary flow impairment was more pronounced in senescents than in adults (48.4 +/- 9.4 and 75.3 +/- 4.9% of baseline value, respectively; P < 0.05) but was fully prevented in senescent hearts by cariporide treatment (95.6 +/- 17.0% of baseline value; P < 0.05 vs untreated group). This beneficial effect of cariporide on coronary tone was associated with an improvement of active and resting tensions and lower LDH release. Such functional protective effects of cariporide suggest an operative NHE during LFI at both coronary and myocardial levels in senescent heart. In addition, cariporide-associated improvement of post-ischemic recovery of coronary and contractile function as well as the limitation of cellular injury suggests a major role of calcium overload via NHE activation during reperfusion of senescent ischemic heart.