Failure to reproduce the in vitro cardiac electrophysiological effects of naloxone in humans.

Abstract

1 Opioid receptor antagonists such as naloxone have shown antiarrhythmic activity in animal models of coronary artery occlusion. Studies have indicated that these effects are stereospecific but both isomers of naloxone prolong action potential duration and refractoriness in guinea-pig and rabbit isolated ventricular myocardium (Class III effect). 2 This study was performed to identify whether this Class III effect of naloxone could be reproduced in human myocardium in vivo. Twenty patients with coronary artery disease received intravenous racemic naloxone (1-40 ,ug kg-' min-'). Surface electrocardiographic parameters were measured and refractory periods were determined during fixed rate pacing by programmed stimulation. 3 The corrected QT interval during sinus rhythm (SR-QTc) was prolonged by 5(3)% (P = 0.06) at a dose of 20 ,ug kg-' min-' and by 9(10)% at 40 ,ug kg-' min-' (P = 0.03).These small changes were lost at higher paced heart rates. No significant effects on atrial, atrioventricular nodal or ventricular refractoriness were seen. 4 Plasma naloxone concentrations well into the micromolar range were achieved with both of the higher doses of naloxone administered. Plasma ,3-endorphin concentrations invariably increased following naloxone infusion. There was no statistical relationship between peak plasma naloxone concentrations and the absolute or percent prolongation of SR-QTc. 5 It seems unlikely that racemic naloxone would have any clinical utility as an antiarrhythmic agent. Racemic naloxone may enhance cardiac adrenergic nerve activity and this receptor mediated effect may have prevented the demonstration of any nonreceptor mediated prolongation of cardiac refractoriness. Studies with the individual stereoisomers of naloxone would be of interest.

Ventricular Tachycardia After Naloxone Administration: a Drug Related Complication? Case Report and Literature Review

“…This combined with a sudden loss of the opioid induced protection against arrhythmias due to naloxone administration may have triggered sympathetic overdrive in these patients. In addition, minor corrected QT interval prolongation due to relatively high dose naloxone infusion (40 ug/kg/min), and therefore possible susceptibility for cardiac arrhythmias, has been described in a very small population [ 10 ].…”

Naloxone improves functional recovery of myocardial stunning in conscious dogs through its action on the central nervous system

“…19 This might explain, at least in part, the dose-related variability and species differences of opioid receptormediated effects. 20 Selective opioid receptor blockade might provide a starting point for effective treatment of the negative inotropic effects of myocardial stunning. However, further investigations in this area will be needed.…”