Acute myocardial uptake of digoxin in humans: correlation with hemodynamic and electrocardiographic effects

Acute myocardial uptake of digoxin was measured at a constant paced heart rate (75 beats/min) for 30 min after an intravenous bolus injection of 500 micrograms of digoxin in 14 patients with ischemic heart disease. Myocardial digoxin content, determined by serial measurement of aortocoronary sinus digoxin concentration gradients and coronary sinus blood flow, was expressed relative to coronary sinus blood flow at rest and correlated with simultaneous hemodynamic and electrocardiographic changes. Myocardial digoxin uptake was extensive (4.1 +/- 0.7% of total injected dose at 30 min) and prolonged, with rapid initial uptake (75.3 +/- 6.6% of maximum at 3 min), followed by a variable phase of slower accumulation. Peak left ventricular positive first derivative of left ventricular pressure (dP/dt) increased progressively (p less than 0.01), with a similar time course to that of myocardial digoxin accumulation; maximal change was 18.5 +/- 4.7% at 27 min. The ratio of inotropic effect to myocardial digoxin content did not vary significantly over the period of the experiment. However, peak inotropic effects in individual patients were not significantly related to peak myocardial digoxin content. The spontaneous PR interval increased transiently, with a peak increase of 5.9 +/- 1.8% (p less than 0.05) 12 min after digoxin administration. It is concluded that after intravenous bolus administration, 1) peak effects of digoxin on atrioventricular (AV) conduction occur early, whereas positive inotropic effects increase progressively for greater than or equal to 27 min; and 2) digoxin accumulation in the human myocardium is prolonged and is a determinant of inotropic effects, but not of prolongation of AV node conduction.