Age-related digoxin effects in an intact canine model

The inotropic and electrophysiologic effects of digoxin were studied in anesthetized neonatal and adult dogs to test the hypothesis that digoxin had comparable effects in these groups. Recordings of the ECG and central arterial pressure were made starting at 5.75 hours after an intravenous injection of 50 μg/kg of the drug. Parameters measured were heart rate (HR); PR interval; mean, systolic, and diastolic blood pressure; preejection period (PEP); and ejection time (ET). Two indices of systolic function were calculated, the systolic time interval (STI = PEP ET) and total electromechanical systole (TMS = PEP + ET), which was indexed for HR. There was no significant difference from control animals in either the adult or neonatal groups in the PR interval or blood pressure. In the neonatal dogs, HR and STI were also not significantly different from control. However, in the neonatal dogs, there was a significant decrease in the indexed TMS, 288 ± 7 vs 270 ± 11 msec (p < 0.01). In the adult animals, HR decreased from 116 ± 35 to 66 ± 25 bpm (p < 0.01), STI decreased from 0.559 ± 0.059 to 0.447 ± 0.069 (p < 0.01), and indexed TMS decreased from 333 ± 10 to 291 ± 13 msec (p < 0.001). Two-way analysis of variance demonstrated that digoxin differed significantly in its effects on HR (p = 0.005), STI (p = 0.018), and TMS indexed for HR (p = 0.003) in neonatal compared to adult dogs. Pharmacokinetic studies showed a rapid distribution phase and equillibrium conditions at the time of physiologic measurements. At the conclusion of the experiments (6.25 hours), serum digoxin levels were 4.08 ± 1.08 ng/ml in the neonatal dogs vs 3.53 ± 0.57 ng/ml in the adult dogs. Left ventricular and right ventricular digoxin levels did not differ significantly; however, right atrial levels were significantly higher in the neonatal dogs, 421.7 ± 218.3 vs 81.83 ± 23.15 ng/gm. We conclude that in dogs, neonates are relatively insensitive to digoxin.