Selective mitochondrial K(ATP) channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits.
We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (K(ATP)) openers (nicorandil and aprikalim), and a specific mitochondrial K(ATP) 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 microg/kg bolus+10 microg/kg/min) or aprikalim (10 microg/kg bolus+0.1 microg/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 K(ATP) 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.
Das
Biswadeep
B
Department of Pharmacology, Kasturba Medical College, Manipal, Karnataka, 576119, India. mcoms@mos.com.np
Sarkar
Chayna
C
Karanth
K Sudhakar
KS
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels; D011817:Rabbits; D012720:Severity of Illness Index
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; C052853:5-hydroxydecanoic acid