The Protective Effect of Na+/Ca2+ Exchange Blocker KB-R7943 on Myocardial Ischemia-Reperfusion Injury in Hypercholesterolemic Rat

摘要

KB-R7943 reduces lethal reperfusion injury under normal conditions, but its effectiveness under certain pathological states is in dispute. In the present study, we sought to determine the effect of KB-R7943 in hyperlipidemic animals and assess if the K-ATP(+) are involved in the protective mechanisms. In group 1 (G1), isolated rat hearts underwent 25 min global ischemia (GI) and 120 min reperfusion (R). In group 2 (G2), G1 was repeated but the animals were subjected to a 1.5 % cholesterol-enriched diet during 6 weeks (hypercholesterolemic animals). In group 3 (G3), G2 was repeated but 1 mu M KB-R7943 was added to the perfusate for 10 min from the start of reperfusion. In group 4 (G4), G3 was repeated, and glibenclamide (K-ATP(+), blocker, 0.3 mu M) was administered. The infarct size was measured by triphenyltetrazolium. The infarct size was 35 +/- 5.0 % in G1 and 46 +/- 8.7 % in G2 (P < 0.05); KB-R7943 reduced the infarct size (28.6 +/- 3.3 % in G3 vs. G2, P < 0.05). In addition, KB-R7943 attenuated apoptotic cell (G3 vs. G2, P < 0.05), but glibenclamide abolished the effect reached by KB-R7943. Thus, diet-induced hyper-cholesterolemia enhances myocardial injury; KB-R7943 reduces infarct size and apoptosis in hyperlipidemic animals through the activation of K-ATP(+) channels.