Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs.
How bretylium tosylate affected the ventricular fibrillation threshold, electrophysiological parameters, and plasma catecholamine levels during hypothermia in dogs was studied. Threshold for ventricular fibrillation was determined by programmed electrical stimulation using a stimulation protocol that involved applying a maximum of five extrastimuli at body temperatures 37, 34, 31, 28, and 25 degrees C, and at the same temperatures during rewarming. Electrocardiogram, epicardial monophasic action potentials (MAP), and electrograms were recorded, and ventricular effective refractory period (VERP) was determined at each of the above temperatures. In one group (n = 7), a bolus dosage of bretylium tosylate (BT), 6 mg/kg body wt, was administered at 25 degrees C before rewarming. Another group (n = 4) was exposed to cooling and rewarming without addition of BT. Cooling to 25 degrees C reduced ventricular fibrillation threshold linearly, reduced heart rate, increased VERP and MAP, and slowed myocardial conduction velocity in both groups. There was no overall increase in plasma catecholamine levels during cooling. Addition of BT at 25 degrees C increased ventricular fibrillation threshold during rewarming compared with cooling. Addition of BT at 25 degrees C increased VERP by +/- 32 milliseconds and the corrected JT time by 0.06 +/- 0.02 seconds. VERP and JTc increased during rewarming with BT compared with cooling with no drug. BT had no effect on conduction velocity, and plasma catecholamine levels were not reduced. The antiarrhythmic effect of BT during hypothermia was attributed to an increased wavelength of refractoriness by its increase in the refractory period. This increased wavelength of refractoriness may prevent excitable gaps or increase circuit pathway in the setting of reentry arrhythmias.
Department of Medical Physiology, University of Tromsø, Norway.
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Bjørnstad
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Mortensen
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Sager
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Refsum
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature; D001950:Bretylium Tosylate / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D004837:Epinephrine / Q000097:blood; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology
D001950:Bretylium Tosylate; D009638:Norepinephrine; D004837:Epinephrine