Ventricular arrhythmia incidence in the rat is reduced by naloxone.
This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.
Department of Anaesthesia, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3. Electronic address: mkpugsley@yahoo.com.
M K
MK
Pugsley
Department of Anaesthesia, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
E S
ES
Hayes
Department of Anaesthesia, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
W Q
WQ
Wang
Department of Anaesthesia, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
M J A
MJ
Walker
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D009270:Naloxone / Q000627:therapeutic use*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D018754:Ventricular Dysfunction / Q000188:drug therapy*; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D009270:Naloxone; D011802:Quinidine
Antiarrhythmic; Electrical arrhythmia; Ischemic arrhythmias; Naloxone; Opioid; Quinidine; Ventricular fibrillation