Influence of hyperkalaemia and ischaemia on non-receptor-mediated cardiac electrophysiological effects of naloxone

• Published in: Cardiovascular research 1993-02, Vol.27 (2), p.296-303
• Main Authors: Oldroyd, Keith G, Hicks, Martin N, Cobbe, Stuart M
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Biological and medical sciences; Culture Techniques; Dose-Response Relationship, Drug; Electrocardiography. Vectocardiography; Electrodiagnosis. Electric activity recording; Electrophysiology; Heart Conduction System - drug effects; hyperkalaemia; Hyperkalemia - physiopathology; Investigative techniques, diagnostic techniques (general aspects); ischaemia; Medical sciences; Morphine - pharmacology; Myocardial Ischemia - physiopathology; naloxone; Naloxone - pharmacology; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; opioids; Rabbits; Refractory Period, Electrophysiological - drug effects
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/27.2.296

Objective: The aim was to investigate the cardiac electrophysiological effects of the opioid receptor antagonist naloxone and examine whether hyperkalaemia and ischaemia influence these effects. Methods: The cardiac electrophysiological effects of racemic naloxone, nalmafene, and morphine were examined in superfused rabbit papillary muscles under normal conditions and in the case of naloxone under conditions of hyperkalaemia. The electrophysiological effects of racemic naloxone and d-naloxone were examined in arterially perfused rabbit interventricular septa before and during 30 min global zero flow ischaemia; the rate of rise of extracellular K+ concentration was also measured. Results: Naloxone, nalmafene and morphine all prolonged action potential duration and effective refractory period in superfused papillary muscles (class III effects), suggesting that these effects are not receptor mediated. During hyperkalaemia, naloxone increased the depressant effect on the maximum upstroke velocity of the action potential and enhanced post-repolarisation refractoriness, further suggesting a class I effect. Both racemic naloxone (active at opioid receptors) and d-naloxone (inactive) prolonged action potential duration and effective refractory period in septa, again suggesting non-receptor-mediated effects. During myocardial ischaemia the class III effects of both compounds were gradully lost in such a way that post-repolarisation refractoriness developed. Both compounds reduced the rate of rise of extracellular K+ concentration and preserved resting membrane potential, but the fall in maximum upstroke velocity was enhanced, again suggesting that naloxone has an additional class I effect in partially depolarised ventricular myocardium. Conclusions: The antiarrhythmic activity of naloxone in models of myocardial ischaemia/reperfusion can be explained by non-opioid receptor mediated effects on the duration and maximum upstroke velocity of the action potential and on extracellular potassium accumulation during ischaemia. Cardiovascular Research 1993;27:296-303