Adniinistrntion of a therapeutic close level of digoxin in the intact clog resulted in an augmentation of the glucose utilization of the myocardium accompanied by a. greatly increased rate of glycolytic and oxidative activity. The contribution of glucose to the total metabolism of the heart was increased, and the utilization of noncarbohydrate substrates was decreased. These metabolic changes occurred in the absence of changes in the dynamic functions of the heart, indicating that the metabolic alterations were due to a primary effect of the drug rather than an effect secondary to an altered state of cardiac activity.A /ITIOUGH great advances have been made in the basic biochemical and physiological mechanisms of cardiac contractility 1 there still remains a general lack of agreement concerning the mechanism of action of the cardiac glycosides. A further knowledge of the mechanism of action of digitalis in returning the failing heart to a state of compensation would facilitate an understanding of the metabolism of the normal myocardium and the pathogenesis of cardiac failure.Studies of the changes in the substrate utilization of the heart in congestive failure 2 and after treatment with a cardiac glycoside 3 have indicated a lack of significant alteration in the metabolic activity of the myocardium. There have been no direct studies of the intermediary metabolism of the heart to substantiate these findings. Based on the utilization of C" labeled substrates by clog ventricle strips, Wollenberger 4 suggested an action of ouabaiu on metabolic processes.The following experiments were specifically designed to correlate the cardiac hemodynamic action of digoxin with possible alterations in the dynamics of the intermediary metabolic pathways involved in the myocardial utilization of glucose-C 14 in the normal dog. Methods Cardiovascular Effects of DigoxinThe cardiovascular effects of 0.065 mg./Kg\ digoxin, administered rapidly as a, single intravenous dose, wore determined in young male dogs weighing-10 to 16 Kg. The animals were anesthetized by the intravenous administration of pentobarbital sodium (25 to 35 nig./Kg.) to the point of loss of the lid reflex but presence of a cornea 1 reflex. The trachea was cannulated and the animal was allowed to breathe room air which was supplemented with oxygen via a tracheal catheter in order to insure an arterial blood oxygen content of not less than 19 volumes per cent. The carotid artery was cannulated, and a polyethylene catheter was placed in the aorta for measurement of blood pressure by means of a, Statham transducer. Venous pressure was similarly measured by means of a catheter inserted via the jugular vein and positioned at the bifurcation of the inferior and superior vena, cavae. Left ventricular pressure was obtained via a fine polyethylene catheter inserted into the left ventricular chamber by way of the carotid artery and aorta. Cardiac output, coronary blood flow (in the circumflex branch of the left coronary artery), cardiac work, cardiac arterio-venous oxygen differ...

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