Antiarrhythmic properties of naloxone: an electrophysiological study on sheep cardiac Purkinje fibers.
Recent data suggest that the opioid antagonist naloxone may exert an antiarrhythmic action on arrhythmias caused by coronary artery occlusion and reperfusion in experimental animals. We used intracellular microelectrodes to study the direct electrophysiological properties of naloxone. Experiments were carried out on sheep cardiac Purkinje fibers, the electrical and mechanical activity of which were recorded simultaneously. Naloxone (10(-7)-10(-4) M) caused a prolongation of the action potential duration, a decrease in the maximum rate of depolarization, a flattening of the slope of diastolic depolarization and a decrease in contractility. Naloxone at 10(-6) M significantly reduced the rate of spontaneously beating Purkinje fibers and at 10(-5) M completely blocked normal automaticity. Naloxone had, however, intriguing effect on the oscillatory afterpotentials, which is a relevant arrhythmogenic mechanism. While naloxone (10(-7)-10(-4) M) did not affect the digitalis-induced oscillatory afterpotentials, it increased the amplitude of the barium-induced oscillatory afterpotentials at lower concentrations (10(-7) M) and decreased the amplitude of these potentials at high concentrations (10(-6)-10(-4) M). It is concluded that naloxone exerts a direct electrophysiological effect on cardiac cells and that this effect is probably important for explaining the antiarrhythmic action of naloxone.
Cerbai
E
E
Department of Preclinical and Clinical Pharmacology, University of Firenze, Italy.
De Bonfioli Cavalcabó
P
P
Masini
I
I
Porciatti
F
F
Mugelli
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001464:Barium / Q000494:pharmacology; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D009270:Naloxone / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep; D013327:Strophanthidin / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D001464:Barium; D009270:Naloxone; D013327:Strophanthidin