Effect of Various Antiarrhythmic Drugs on the Daunomycin-Induced Arrhythmia in the Hamster

Abstract

Daunomycin 151), an antibiotic, has been found to acutely induce a bidirectional ventricular arrhythmia in the hamster ( 1 ) . Arrhythmias have also been induced experimentally following ouabain (2), ligation of the anterior descending coronary artery (3), administration of epinephrine during cyclopropane anesthesia (4) or hypothermia (5). Numerous studies have shown that these arrhythmias can be suppr.essed by various types of drugs including beta adrenergic blocking compounds. The present study was initiated to determine to what extent the daunomycin arrhythmias in the hamster are modified by antiarrhythmic drugs.Methods and Materials. Male golden hamsters weighing between 90 ,to 140 g were used in all experiments. Anesthesia was induced with an intraperitoneal (ip) injection of 45 mg/kg of sodium pentobarbital (Nembutal) . A standard lead I1 electrocardiogram (ECG) was monitored from needle electrodes inserted into the appropriate limbs and hear't rate was determined by means of a cardiotachometer. In some experiments, right carotid artery blood pressure was monitored through a Sanborn 267B transducer and respiratory movements were detected by means of a differential pressure transducer attached to a tracheal cannula. All parameters were recorded with a Hewlett-Packard polygraph.Each hamster was administered 50 mg/kg of daunomycin. A supplemental dose of 25 mg/kg was'then given if the ECG pattern did not become abnormal within 15 min. The challenge agents or saline were given over a Supported in part by Contract PH43-68-2283 from Chemotherapy, National Cancer Institute, NIH.2-min period when the arrhythmia had been established for 5 min. The onset and duration of any antiarrhythmic activity were recorded. Heart rates were determined prior to daunomycin, prior to and following test drug administration. Experiments were terminated 30 min following test drug administration.Drugs, calculated as the free base, were dissolved in physiological saline prior to the beginning of each experiment. Injections were made through a fermoral vein cannula in a dose volume of 0.1-0.2 ml followed by a 0.2-ml saline wash.The compounds studied and doses (mg/kg ) were : dl-propranolol hydrochloride (Inderal) (0.25, 0.5, 1.0, and 2.0), d-propranolol hydrochloride ( 1 .O, 2.0, and 4.0) , diphenylhydantoin sodium (Dilantin) ( 12.5 and 25.0), quinidine sulfate, (1.5, 3.0, and 6.0) procainamide hydrochloride ( Pronestyl) 1.2, 6.0, and 20.0), lidocaine hydrochloride (Xylocaine) (1.0, 5.0, and 10.0) dZ-[4-2 ( -isopropylamino-1 -hydroxyethyl) methanesulfonanilide hydrochloride] (dl-M J 1999) (1, 3, and 6.2)) and ~(-)-l-N-isopropyl-P-nitrophenyl-ethanolamine hydrochloride D (-)