Comparative effects of levosimendan, OR-1896, OR-1855, dobutamine, and milrinone on vascular resistance, indexes of cardiac function, and O2 consumption in dogs

摘要

pharmacotherapy of congestive heart failure (CHF) is based on two strategies: 7) increasing the contractile force of the heart; and 2) unloading of the heart by reducing preload and afterload (5). Increasing inotropic activity through an elevation in intracellular calcium, traditionally, has been the common denominator of inotropic drugs, i.e., digoxin, adrenergic-(3i-agonists, phosphodiesterase (PDE) inhibitors, although their narrow therapeutic index, toxicity (arrhythmias), and weak efficacy in chronic therapy limit their clinical value (26, 47). Calcium-sensitizing agents, on the other hand, are able to generate increased force of contraction without an increase in cytoplasmic free calcium and represent a novel approach to increasing left ventricular function in the treatment of heart failure, without the risks associated with increased intracellular free calcium (26). Reducing load on the heart is achieved by many drugs used today by targeting the vasculature and reducing resistance through various mechanisms (5).