STUDIES ON DIGITALIS. X. EFFECTS OF OUABAIN ON FOREARM VASCULAR RESISTANCE AND VENOUS TONE IN NORMAL SUBJECTS AND IN PATIENTS IN HEART FAILURE.

Although the therapeutic action of digitalis is generally agreed to result largely from its ability to stimulate the contraction of the myocardium, there has been considerable suspicion that cardiac glycosides may also act directly upon the systemic vascular bed. Excised arterial and venous strips contract when exposed to digitalis glycosides (1-4), and generalized systemic arteriolar and venous constriction has been induced by digitalis in-anesthetized open-chest dogs on cardiopul-monary bypass (5, 6). In normal human subjects digitalis glycosides elevate arterial pressure and either have little effect on or diminish cardiac output , thus augmenting the calculated systemic vas-cular resistance (7). More direct evidence that digitalis acts upon vascular smiiooth muscle was provided by the observation that the drug elevated systemic vascular resistance in patients on total cardiopulmonary bypass, in whom the systemic perfusion rate was held constant, and in whom the cardiac effects of the drug could not influence arterial pressure directly (8). Little information is available, however, concerning the extracardiac actions of digitalis glycosides when given in the usual clinical doses to intact human subjects. The present investigation was undertaken to characterize the effects of ouabain on a specific vascular bed, that of the forearm. The effects of the drug on both the resistance and capacitance vessels were examined in normal subjects and in patients with congestive heart failure. The effects of ouabain were determined in 12 normal subjects, between 18 and 49 years of age, and in 6 patients with congestive heart failure, between 34 and 52 years in age. Four of these patients had rheumatic mitral * valve disease and 2 had coronary artery disease. All 6 of the patients had elevated venous pressures ranging from 15.8 to 23.1 and averaging 19.3 cm H O, measured in a large antecubital vein with a water manometer and a no. 18 needle, utilizing a base line 5 cm beneath the sternal angle. At right and left heart catheterization all 6 patients had elevated pulmonary arterial and left atrial pressures and cardiac indexes below normal (2.50 L per minute per m'). At the time of the study none of the patients were being treated with diuretics or salt restriction. However, they voluntarily restricted their activities in the hospital because of symptoms of diminished cardiac reserve. All 6 were in Classes III or IV, according to the functional criteria of the New York Heart Association. A plethysmographic technique was employed for the …