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

  • Translational Biomedical Research
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Abstract

Reverse-mode activation of the Na+/Ca2+ exchanger (NCX) during reperfusion following ischemia contributes to Ca2+ 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.

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North of Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, China

    Yan Lv, Yongkui Ren, Lufan Sun, Shaojun Wang & Dalin Jia

  2. Pharmaceutical College of China Medical University, Shenyang, China

    Minjie Wei

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  1. Yan Lv
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  2. Yongkui Ren
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  3. Lufan Sun
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  4. Shaojun Wang
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  5. Minjie Wei
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  6. Dalin Jia
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Correspondence to Dalin Jia.

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Lv, Y., Ren, Y., Sun, L. et al. Protective Effect of Na+/Ca2+ Exchange Blocker KB-R7943 on Myocardial Ischemia–Reperfusion Injury in Hypercholesterolemic Rats. Cell Biochem Biophys 66, 357–363 (2013). https://doi.org/10.1007/s12013-012-9474-7

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