FAILURE TO REPRODUCE THE IN-VITRO CARDIAC ELECTROPHYSIOLOGICAL EFFECTS OF NALOXONE IN HUMANS

1 Opioid receptor antagonists such as naloxone have shown antiarrhythm ic activity in animal models of coronary artery occlusion. Studies hav e indicated that these effects are stereospecific but both isomers of naloxone prolong action potential duration and refractoriness in guine a-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 pati ents with coronary artery disease received intravenous racemic naloxon e (1-40 mu g kg(-1) min(-1)). 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 2 0 mu g kg(-1) min(-1) and by 9(10)% at 40 mu g kg(-1) min(-1) (P = 0.0 3). These small changes were lost at higher paced heart rates. No sign ificant effects on atrial, atrioventricular nodal or ventricular refra ctoriness were seen.