CARDIAC TOXICITY OF DIGOXIN IN NEWBORN AND ADULT-RATS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 1  (2) , 97-103
Abstract
The age-specific arrhythmogenic effects of digoxin in the rat were investigated. Adult female rats (n = 26) and 1-day-old newborns (n = 20) were anesthetized with pentobarbital and injected s.c. with varying doses of digoxin. ECG were monitored continuously for 4 1/2 h following digoxin administration. The arrhythmogenic dose50 (AD50) and LD50 under anesthesia. were determined using the method of Litchfield and Wilcoxon. AD50 in adults was 13.0 .+-. 1.0 mg/kg (.hivin.X .+-. SD) compared with 2.9 .+-. 0.3 mg/kg in the newborns (P < 0.01); LD50 in adults was 30.0 .+-. 1.9 mg/kg compared with 5.0 .+-. 0.2 mg/kg in the newborns (P < 0.01). Arrhythmias appeared earlier in adults (54 .+-. 11.5 min after digoxin, .hivin.X .+-. SEM [standard error of the mean]) than in newborns (132.2 .+-. 11.0 min P < 0.01). Paroxysmal atrial tachycardia was the predominant arrhythmia in adults (73%), while transient sinus bradycardia appeared in only 9%. All newborns with arrhythmias had severe sinus bradycardia and 69% had profound 1st degree heart block as well. The newborn rat was evidently sensitive to digoxin toxicity and developed lethal arrhythmias much more readily than the adult.