Sympathomimetic vs Non-Sympathomimetic Drugs in the Treatment of Heart Failure

Abstract

The syndrome of congestive heart failure is characterized by a reduced stroke volume and peripheral circulatory changes that redistribute blood flow to metabolically active tissues. Conventional inotropic therapy has been limited by the moderate potency and marked toxicity of the glycosides [1] and the ob ligate i.v. route of administration of the catecholamines. Recent studies suggest that the potent effects of the catecholamines are also subject to tolerance after prolonged administration [2–5]. Thus, it is not surprising that considerable effort has been expended on developing new inotropic therapies that produce their effects by novel mechanisms of action and — in addition — exert considerable vasodilator properties at the same time. Whereas conventional therapeutic strategy attempts to improve ventricular performance by eliciting a “contractile reserve” from the failing heart, it now seems apparent it is the peripheral circulatory changes that predominantly govern functional capacity. An inotropic agent’s ability to reverse these peripheral circulatory changes is determined by its inotropic potency, vasodilating capacity, and sustained efficacy. The limitations of conventional therapies have therefore led to the development of new classes of nonglycosidic, nonadrenergic inotropic agents that seem to exert their effects by myocardial phosphodiesterase inhibition, by H2 receptor mediated adenylate cyclase stimulation and by calcium-sensitizing of myocardial contractile proteins. Although these potent ino tropes enhance exercise and aerobic capacity, they are palliative rather than curative agents.