Further Observations on the Circulatory Actions of Digitalis and Strophanthus With Special Reference to the Liver, and Comparisons With Histamine and Epinephrine

Abstract

In a previous paper (1) it was shown that digitalis in dogs caused a fall in venous pressure at the time when the minute volume flow of blood was diminished. This fall in venous pressure, and hence in return flow of blood to the heart, was correlated with a peripheral vasocontrictor action of the digitalis. It was indicated that constriction of the hepatic veins was the major factor in causing a redistribution of blood, with pooling in the splanchnic area. This venous action of digitalis agreed with results on the perfused liver and on excised veins reported in the literature. Kobert (2), in 1886, and Lampe and Mehes (3), in 1926, demonstrated that digitalis and allied glucosides caused a marked constriction of the vessels of the perfused liver, and Franklin (4), in 1925, reported constriction of excised veins by digitalis. In our experiments on dogs there was a progressive increase in volume of the liver in-situ and a simultaneous constriction of the intestines after doses of digitalis corresponding to the full therapeutic. Although the significance of these changes in the splanchnic region were appreciated at the time, it was thought that additional data on the state of the portal circulation were desirable, particularly with reference to confirmation or denial of the constrictor action of digitalis on the hepatic veins. In the present paper, therefore, further experiments on this portal mechanism are presented, the results with digitalis being compared and correlated with those with histamine and epinephrine as controls. DIGITALIS AND STROPHANTHUSThe same tincture of digitalis was used as in our previous experiments (1). The potency was equivalent to 88 mgm. of leaves, or 485

The circulatory changes after full therapeutic doses of digitalis, with a critical discussion of views on cardiac output

“…The increase in liver volume was particularly suggestive, for this indicated a pooling of the blood in this viscus due to diminished outflow as the result of hepatic vein constriction. The constriction of these veins, which are richly endowed with smooth muscle, is strictly consistent with the arterial constrictions in the leg and intestine, and would result in lowered venous pressure.2 The constriction of liver veins by digitalis has been demonstrated by Lampe (29) and confirmed by us (30).…”

Studies on Digitalis. I. Direct Effects on Peripheral Vascular Resistance

“…It had been suggested that the primary action of digitalis is extracardiac (1)(2)(3) and that the direct effects on the vascular bed may be responsible, in part, for its therapeutic action (4). However, in most studies, attention has been directed to the powerful positive inotropic action of this drug (5)(6)(7)(8)(9)(10).…”

Studies on the Effect of the Action of Digitalis on the Output of Blood From the Heart

“…Dock and Tainter (3,4) believe that an explanation of this sort must be rejected because it fails to take into account the behavior of the rest of the circulatory apparatus which, as they think, is simultaneously affected. They have drawn attention (4) to a mechanism in the hepatic veins by which, under the influence of digitalis, the lumina, the walls containing smooth muscle which contracts, diminish and prevent the return of blood to the heart (10) because it is dammed back into the intestinal cavity.…”

“…The fact that in their experiments "a fall in venous pressure regularly accompanied the diminished cardiac output " they regard as " convincing evidence that the change in blood flow was a result of peripheral, and not cardiac, actions of the drug " (Conclusion 3) (3). Tainter and Dock (4) showed later that " the fall in right auricular pressure, after giving digitalis to dogs with the hepatic circulation intact, was due to diminished venous return flow, and ultimately to an accumulation of blood in the splanchnic or portal region as a result of obstructed hepatic outflow (hepatic vein constriction).…”

“…The mean blood pressure in the brachiocephalic artery was recorded on the same smoked paper by a mercury manometer; that in the right auricle by a water manometer. 4. Peripheral resistance was provided in the usual manner (Knowlton and Starling (8)).…”