Selective mitochondrial KATP channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits

Biswadeep Das, Chayna Sarkar, K. Sudhakar Karanth

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15 Citations (Scopus)

Abstract

We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (KATP) openers (nicorandil and aprikalim), and a specific mitochondrial KATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. Arrhythmias were induced by reperfusion following a 20 min ligation of the left main coronary artery with a releaseable silk ligature. Early intervention by intravenous infusion of nicorandil (100 μg/kg bolus+10 μg/kg/min) or aprikalim (10 μg/kg bolus+0.1 μg/kg/min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and myocardial infarct size. The antiarrhythmic and cardioprotective effects of both nicorandil and aprikalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus). In conclusion, intervention by intravenous administration of nicorandil and aprikalim (through the selective activation of mitochondrial KATP channels) increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion.

Original languageEnglish
Pages (from-to)165-171
Number of pages7
JournalEuropean Journal of Pharmacology
Volume437
Issue number3
DOIs
Publication statusPublished - 22-02-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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