Effect of Digoxin on the Circulation in Normal Man

Abstract

Digitalis is one of the oldest and most widely used drugs in clinical medicine. Its action in congestive cardiac failure has been thoroughly studied by many workers. Its action upon the normal circulation, however, has received relatively little attention. The concept that it lowers cardiac output and reduces central venous pressure in normal subjects continues to be expressed by many workers. This view, based on studies employing older, often inadequate methods, has been neither confirmed nor disproved by means of existing hmmodynamic techniques. This study, utilizing the technique of cardiac catheterization, was undertaken for the purpose of investigating the heemodynamic effect of digoxin upon the circulation in 12 normal subjects. MATERIALS AND METHODSAll twelve patients were carefully investigated by clinical, electrocardiographic, and radiological methods, and in none was there any evidence of significant cardiovascular abnormality. Sedatives (0X1 g. sodium pentobarbital) were administered to five patients prior to the study. Special care was exercised that all measurements should be performed during a suitable post-absorptive steady state: that this was achieved is indicated by the small variation in duplicate control measurements prior to the administration of digoxin. Cardiac catheterization was performed in the usual manner. A branch of the basilic vein was dissected free under local procaine anwsthesia and a large size (No. 9F) cardiac catheter was introduced and guided under fluoroscopic control into the right ventricle and pulmonary artery. Pressures were recorded using strain gauge transducers and a direct writing oscillograph (Sanborn). The tip of the catheter was then withdrawn to the centre of the right atrium. For the remainder of the study frequent or continuous records of right atrial pressure were obtained. The sensitivity of the system was adjusted so that a deflection of 1 cm. on the tracing was equal to 1 mm. Hg pressure change. The zero reference point was midway between the recumbent patient's spine and the sternum. The reference point was rechecked at frequent intervals during the study. With the catheter tip in the right atrium, and when the patient had reached a satisfactory steady state after 15 minutes resting period, two control determinations of the cardiac output were made with a 15 to 20 minute interval between them. Oxygen consumptions were obtained by analysis of duplicate samples for oxygen and carbon dioxide in the patient's expired air collected in a Tissot spirometer during a three-minute period. Midway during the air collection period simultaneous samples were withdrawn from the right atrium and brachial artery, the latter through an indwelling arterial needle. Duplicate analyses for oxygen and carbon dioxide were performed using Van

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“…[51]. Consistently, no drug-related adverse events have been reported in trials on subjects with normal hearts who were given clinical doses of ouabain [52,53], digitoxin [23,54], or digoxin [55][56][57][58]. Nonetheless, it is important that treatment with these drugs should always be under the control of health care professionals.…”

Inotropic and Vasopressor Agents

“…The ability of digitalis to increase the force of myocardial contraction was first demonstrated in depressed cat papillary muscles in 1938, by Catell and Gold, but the techniques available at that time failed to demonstrate consistently a similar effect in non-depressed cardiac muscles (Catell and Gold, 1938;White and Salter, 1946). Haemodynamic studies undertaken after the introduction of cardiac catheterization showed either no change or a decrease in cardiac output in animals or humans not in cardiac failure (McMichael and Sharpey-Schafer, 1944;Williams, Zohman and Ratner, 1958;Selzer, Hultgren and Ebnother, 1959). These results led to the belief that digitalis stimulated the failing myocardium, but did not increase contractility in the normal heart.…”

Problems in Drug Management of Cardiovascular Disorders in Geriatric Patients*

“…At first it was considered advisable, particularly for the high‐risk elderly patient; later it was deplored, especially for this type of patient if no heart failure was present, the reasons being that it was harmful and did not produce any improvement in cardiodynamics. Selzer et al (3) recently demonstrated that though the contractile force of the hypertrophied compensated heart is increased, the cardiovascular homeostatic mechanisms seem to keep the cardiac rate and output, the blood pressure, and the coronary arterial blood flow at normal levels; in the same way, any increased contractile force resulting from the inotropic action of digitalis is prevented from producing supernormal dynamic effects. It is interesting to speculate about the prophylactic use of digitalis preoperatively in cases of “presbycardia”without heart failure; the stress and shock of surgery might be better tolerated, for instance, in the patient whose initially normal cardiac output suddenly falls below the optimal level.…”