Dose–response effects of cardiac glycosides on pooling and systemic and pulmonary hemodynamics

Abstract

The effects of ouabain and digoxin on systemic and cardiopulmonary circulations and the degree and site of vascular pooling were evaluated in this study. A major emphasis was placed on the relationship of dosage to responses observed. Experiments were performed on 32 adult mongrel dogs using a venous return (constant cardiac inflow) preparation. Animals were divided into two groups, intact and eviscerated. Mean cumulative doses were 27, 55, and 81 μg/kg for intact ouabain-injected dogs; 21, 42, 63, 84, and 105 μg/kg for intact digoxin-injected dogs; and 26, 52, and 77 μg/kg for eviscerated ouabain-injected dogs. There was a positive correlation between amount of blood pooled and dose of cardiac glycosides given in the intact animal. The statistical difference in pooling at each dose of ouabain between intact and eviscerated animals implicated the hepatosplanchnic vascular bed as a major site of pooling. Since there was a significant statistical increase in total peripheral resistance in intact ouabain-injected dogs but not in ouabain-treated eviscerated animals, the site of peripheral resistance changes appears to be the hepatosplanchnic vascular region. Left atrial pressures rose significantly in intact and eviscerated dogs at higher ouabain doses. These findings underscore the complexity of the mechanisms of action of cardiac glycosides and emphasize the critical importance of dosage, type of glycoside administered, and individual variation of response in the canine species.