Key result
Naloxone exerts non-opioid class I and III antiarrhythmic effects during ischemia.
Why the study?
Does naloxone exert non-receptor-mediated cardiac electrophysiological effects under normal, hyperkalaemic, and ischaemic conditions in rabbit myocardium?
Does naloxone exert non-receptor-mediated cardiac electrophysiological effects under normal, hyperkalaemic, and ischaemic conditions in rabbit myocardium?
The antiarrhythmic activity of naloxone in myocardial ischaemia/reperfusion models is likely due to non-opioid receptor-mediated class I and III electrophysiological effects.
Answers are grounded in this paper and cite their sources.
Non-opioid antiarrhythmic effects in ischaemic rabbit myocardium are hypothesis-generating; leaves open translation to human arrhythmia management.
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 gradually 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.
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Oldroyd et al. (1993) studied Myocardial ischaemia and hyperkalaemia. Naloxone, nalmafene, and morphine vs. Normal conditions was evaluated on Cardiac electrophysiological effects (action potential duration, effective refractory period, maximum upstroke velocity, extracellular K+ concentration). Naloxone exhibited non-opioid receptor-mediated class III and class I antiarrhythmic effects on action potential duration, maximum upstroke velocity, and extracellular potassium accumulation during ischaemia.
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