Chronic preconditioning: A novel approach for cardiac protection

Yigang Wang, Nauman Ahmad, Boyu Wang, Muhammad Ashraf

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Ischemic preconditioning is the most powerful protective mechanism known against lethal ischemia. Unfortunately, the protection lasts for only a few hours. Here we tested the hypothesis that the heart can be kept in a preconditioned state for constant protection against ischemia. In this study we chose BMS-191095 (BMS), a highly selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels. BMS (1 mg/kg ip) was administered to rats every 24 h until 96 h. In other groups, BMS plus wortmannin (WTN, 15 μg/kg ip), an inhibitor of the phosphatidylinositol 3-kinase (PI3-K), or BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK ATP, or BMS plus Nω-nitro-L-arginine methyl ester (L-NAME) (30 μg/kg ip), an inhibitor of nitric oxide (NO) synthase, were administered to rats. Rats were then subjected to 30-min left anterior descending coronary artery occlusion and 120-min reperfusion. Cardiac function, infarct size, pathological changes, and apoptosis were assessed at the end of treatments. Saline-treated hearts displayed marked contractile dysfunction and underwent pathological changes. BMS-treated rats showed significant improvement in cardiac function, and infarct size was significantly reduced in BMS-treated hearts. However, protection by BMS was abolished by 5-HD, WTN, or L-NAME. These data demonstrate that hearts can be chronically preconditioned and retain their ability to remain resistant against lethal ischemia and that this protection is mediated by activation of mitoKATP via NO and PI3-K/Akt signaling pathways.

Original languageEnglish (US)
Pages (from-to)H2300-H2305
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007

Keywords

  • BMS-191095
  • Heart function
  • Mitochondrial ATP-sensitive K channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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