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 micrograms/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 less than 0.01). In the adult animals, HR decreased from 116 +/- 35 to 66 +/- 25 bpm (p less than 0.01), STI decreased from 0.559 +/- 0.059 to 0.447 +/- 0.069 (p less than 0.01), and indexed TMS decreased from 333 +/- 10 to 291 +/- 13 msec (p less than 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 equilibrium conditions at the time of physiologic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging / Q000502:physiology*; D000818:Animals; D004077:Digoxin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects
D004077:Digoxin