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Protective Effect of Na(+)/Ca (2+) Exchange Blocker KB-R7943 on Myocardial Ischemia-Reperfusion Injury in Hypercholesterolemic Rats.
MedLine Citation:
PMID:  23212178     Owner:  NLM     Status:  Publisher    
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 < 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 (ATP) (+) channels.
Yan Lv; Yongkui Ren; Lufan Sun; Shaojun Wang; Minjie Wei; Dalin Jia
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-2
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  -     ISSN:  1559-0283     ISO Abbreviation:  Cell Biochem. Biophys.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China.
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