Comparative effects of the opioids fentanyl and buprenorphine on ventricular vulnerability during acute coronary artery occlusion.
Fentanyl, a mu selective opioid agonist in wide clinical use, raises the ventricular fibrillation threshold in the normal canine myocardium. We have previously shown that this effect is amplified by haemorrhagic stress. In order to determine if mu receptor activation is antifibrillatory during acute myocardial ischaemia, we compared the effects of two mu selective agents, fentanyl and buprenorphine, in open chest chloralose anaesthetised dogs. Each drug was administered intravenously in two doses 1 h apart (fentanyl 30 micrograms.kg-1.dose; buprenorphine 0.3 mg.kg-1.dose). Ventricular fibrillation threshold was measured during right ventricular pacing using the single stimulus technique. The threshold was determined before and during a 10 min left anterior descending coronary artery occlusion. Prior to fentanyl administration, ventricular fibrillation threshold decreased from a control value of 19(SEM 2) mA to 12(1) mA during coronary artery occlusion. After the first dose of this drug an attenuation in the ischaemia induced fall in fibrillation threshold from 23(4) mA to 15(2) mA was observed. After the second dose of fentanyl the decline in fibrillation threshold was significantly blunted at 22(4) mA during control and 18(3) mA during occlusion, p less than 0.05 compared to no drug. In an additional series of experiments atropine sulphate abolished the antifibrillatory action of fentanyl, indicating that vagal efferent activation is responsible for the protective effect of the drug during acute myocardial ischaemia. This is in contrast with its mode of action during haemorrhage, when it enhances vagal afferent inhibition of sympathetic tone, and atropine pretreatment is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Saini
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Cardiovascular Laboratories, Harvard School of Public Health, Boston, Massachusetts.
Carr
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Verrier
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D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005283:Fentanyl / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D005283:Fentanyl