The opioid agonist ethylketocyclazocine accentuates epinephrine-induced cardiac arrhythmias in the rat through an action in the brain.
The purpose of this study was to determine whether the opioid receptor agonist ethylketocyclazocine (EKC) modulates the development of cardiac arrhythmias by an action within the central nervous system. Catecholamine-induced ventricular arrhythmias were produced in the rat by continuous infusion of epinephrine, at incremental doses, until the development of fatal arrhythmias that were usually ventricular fibrillation. EKC, 1 mg/kg, intravenously (IV) significantly (p < 0.05) accentuated the manifestations of or reduced the threshold for epinephrine-induced arrhythmias. The effect of EKC was prevented by the kappa opioid antagonist MR 2266 in a dose-dependent manner. To determine whether the central nervous system is a site of this action of EKC, rats received injection of either EKC or the diluent (control) into the lateral cerebral ventricle (ICV). EKC, 100 and 200 micrograms/kg ICV, significantly (p < 0.05) altered the dose-effect relationship between epinephrine and arrhythmias so that EKC accentuated the development of cardiac arrhythmias. These data indicate that EKC, through an action in the brain, modulates cardiac arrhythmias and suggests a role for opioid receptor agonists, such as EKC, in cardiac arrhythmias and perhaps sudden cardiac death in man.
Rabkin
S W
SW
Research Center University Hospital (Shaughnessy), University of British Columbia, Vancouver, Canada.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001575:Benzomorphans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D016314:Ethylketocyclazocine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001575:Benzomorphans; D009292:Narcotic Antagonists; C027247:MR 2266; D016314:Ethylketocyclazocine; D004837:Epinephrine