Quantitative electrocardiographic effects of digoxin in newborn and adult rats

We investigated the age and dose-specific quantitative electrocardiographic effects of digoxin in the rat. Adult female rats (n = 26) and one-day-old newborns (n = 20) were anesthetized with pentobarbital and injected subcutaneously with varying doses of digoxin. Electrocardiograms (ECG) were monitored continuously for four and one-half hours following digoxin administration. PR, QT, and RR intervals, QRS duration (msec), and T amplitude (mm) were measured every 15 minutes in all animals. QTc and PTQ index using the method of Joubert were calculated. Newborns demonstrated significant prolongation of the PR, QT, and RR intervals, an increase in the PTQ index, and a decrease in QTc when compared to adults (receiving the same dosage of digoxin) (P less than or equal to 0.05). In addition they developed toxic changes at much lower doses. Adults developed various tachycardias (tachyarrhythmias) compared to severe sinus bradycardias in the newborns. In conclusion, the newborn rat is much more sensitive to digoxin toxicity than the adult as demonstrated by ECG criteria. The newborns seem to be primarily "parasympathetic" responders as compared to adults who seem to be mainly "sympathetic" responders.