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

Anne C. Powell, John D. Horowitz, Yonathan Hasin, Marie L. Syrjanen, Soumela Horomidis, William J. Louis

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Abstract

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 µg 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 < 0.01), with a similar time course to that of myocardial digoxin accumu- lation; 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 < 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 ≥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.

Original languageEnglish
Pages (from-to)1238-1247
Number of pages10
JournalJournal of the American College of Cardiology
Volume15
Issue number6
DOIs
StatePublished - 1990

Bibliographical note

Funding Information:
From the Departments of Cardiology and Clinical Pharmacology, Austin Hospital, Heidelberg, Victoria, Australia. This study was supported by grants from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia. It was presented in part at the 59th Annual Scientific Session of the American Heart Association, Dallas, Texas, November 1986. Dr. Powell is a National Heart Foundation of Australia Postgraduate Medical Research Scholar. Dr. Horowitz is a Senior Research Fellow of the National Health and Medical Research Council of Australia. Dr. Hasin held a Warren McDonald International Fellowship of the National Heart Foundation of Australia. Dr. Powell's present address is: Cardiac Arrythmia Unit, Massachusetts General Hospital, 32 Fruit Street, Boston, Massachusetts 02138. Digoxin (used in assay) was provided as a gift from Wellcome Australia, Limited.

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