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

• Published in: Cell biochemistry and biophysics 2013-06, Vol.66 (2), p.357-363
• Main Authors: Lv, Yan, Ren, Yongkui, Sun, Lufan, Wang, Shaojun, Wei, Minjie, Jia, Dalin
• Format: Article
• Language: English
• Subjects: Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Cell Biology; Life Sciences; Pharmacology/Toxicology; Translational Biomedical Research
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-012-9474-7

Reverse-mode activation of the Na + /Ca 2+ exchanger (NCX) during reperfusion following ischemia contributes to Ca 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 ATP + 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 μM KB-R7943 and 0.3 μM of K ATP + 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