Effective plasma concentrations of antiarrhythmic drugs against sustained halothane-adrenaline arrhythmia in dogs.
We determined the minimum effective plasma concentrations of several antiarrhythmic agents against canine halothane-adrenaline arrhythmia. Sustained ventricular tachycardia was produced by continuous adrenaline infusion at rates of 1.5 to 4 micrograms/kg/min under 1.5% halothane anesthesia. Procainamide, 20 mg/kg, produced ventricular fibrillation in three of nine dogs. Disopyramide, 3 mg/kg, suppressed the arrhythmia in nine of 11 dogs at a minimum effective plasma concentration of 4.2 micrograms/ml, but produced ventricular fibrillation in the remaining two dogs. Phenytoin, 5 mg/kg, was effective at a minimum concentration of 12 micrograms/ml. Lidocaine, 10 mg/kg, suppressed the arrhythmia at a minimum concentration of 15 micrograms/ml, which is much higher than the human toxic plasma level. These drugs may have suppressed the adrenaline arrhythmia by inhibiting the sodium channel, because their effective concentrations were very close to membrane-stabilizing concentrations in vitro. Small doses of 30 micrograms/kg propranolol and 0.1 mg/kg N-696, two beta-blockers, and 0.1 mg/kg verapamil, a calcium channel blocker, yielding a concentration of 0.03 micrograms/ml, suppressed the arrhythmia, probably by indirectly or directly blocking the calcium channel.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005260:Female; D006221:Halothane / Q000037:antagonists & inhibitors; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D011342:Procainamide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D010672:Phenytoin; D008012:Lidocaine; D011433:Propranolol; D014700:Verapamil; D004206:Disopyramide; D011342:Procainamide; D006221:Halothane; D004837:Epinephrine