Protective Effect of Na^sup +^/Ca^sup 2+^ Exchange Blocker KB-R7943 on Myocardial Ischemia-Reperfusion Injury in Hypercholesterolemic Rats

• Published in: Cell biochemistry and biophysics 2013-06, Vol.66 (2), p.357
• Main Authors: Lv, Yan, Ren, Yongkui, Sun, Lufan, Wang, Shaojun, Wei, Minjie, Jia, Dalin
• Format: Article
• Language: English
• Subjects: Animal models; ATP; Cholesterol
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-012-9474-7

Reverse-mode activation of the Na^sup +^/Ca^sup 2+^ exchanger (NCX) during reperfusion following ischemia contributes to Ca^sup 2+^ overload and cardiomyocyte injury. KB-R7943, a selective reverse-mode NCX inhibitor, reduces lethal reperfusion injury under non-ischemic conditions. However, the effectiveness of this compound under ischemic conditions is unclear. In the present study, we studied the effects of KB-R7943 in an animal model of hyperlipidemia. We further assessed whether the K^sub ATP^^sup +^ channels are involved in potential protective mechanisms of KB-R7943. Twelve rats were fed normal chow, while 48 animals were fed a high cholesterol diet. The hearts from the control and hypercholesterolemic rats were subjected to 25 min of global ischemia followed by a 120-min reperfusion. Before this, hearts from hypercholesterolemic rats either received no intervention (cholesterol control group) or were pre-treated with 1 [mu]M KB-R7943 and 0.3 [mu]M of K^sub ATP^^sup +^ blocker glibenclamide or glibenclamide alone. The infarction sizes (triphenyltetrazolium assay) were 35 ± 5.0 % in the control group, 46 ± 8.7 % in the cholesterol control group (p < 0.05 vs. control group), 28.6 ± 3.3 % in the KB-R7943 group (p < 0.05 vs. cholesterol control group), 44 ± 5 % in the KB-R7943 and glibenclamide group, and 47 ± 8.5 % in the glibenclamide group (p < 0.05 vs. control group). Further, KB-R7943 attenuated the magnitude of cell apoptosis (p < 0.05 vs. cholesterol control group). These beneficial effects were abolished by glibenclamide. In conclusion, diet-induced hypercholesterolemia enhances myocardial injury. Selective reverse-mode NCX inhibitor KB-R7943 reduces the infarction size and apoptosis in hyperlipidemic animals through the activation of K^sub ATP^^sup +^ channels.[PUBLICATION ABSTRACT]