Opioid antagonists have been shown to prevent the occurrence of lethal arrhythmias following coronary reperfusion. In this study, we have examined the effect of a new, long-lasting, potent opioid antagonist, nalmefene, and congeners in the prevention of reperfusion arrhythmias in dogs. Nalmefene given at a dose of 1 mg/kg i.v. reduced the incidence of reperfusion arrhythmias significantly when compared to the saline control. Neither N-methyl nalmefene, a quaternary analog that does not cross the blood brain barrier, nor (+) nalmefene, an isomer with no anti-opioid actions, provided any protection against reperfusion arrhythmias. Regional myocardial blood flow profiles, during and after coronary occlusion, were not different between the nalmefene- and saline-treated groups. We conclude that nalmefene prevents the occurrence of reperfusion-induced arrhythmias by blocking opioid receptors in the brain.
Animals Arrhythmias, Cardiac