The influence of heart rate on digoxin-induced inhibition of myocardial Na+-K+-ATPase activity in the dog.

1. Groups of sedated dogs were studied at spontaneous heart rates (HR), 55-100/min, or at paced HR 200/min, with or without intravenous digoxin administration. After 60 min, active rubidium uptake (86 Rb+) of ventricular samples was determined in vitro. 2. Untreated fast and slow HR groups had similar uptakes. Following digoxin, 0.08 mg/kg, uptake was less at fast than slow HR (63.8, s.e.m. = 4.5 v. 87.5, s.e.m. = 5.0 pmol/mg LV/15 min, P less than 0.01). After 0.125 mg/kg, values were again lower in the fast HR group in which five of seven developed ventricular tachycardia. 3. Heart rate does not alter in vitro activity of myocardial Na+-K+-ATPase but does influence inhibition of the enzyme resulting from digoxin administration.