Effect of Inotropic Agents on Mechanoenergetics in Human Diseased Heart

For the treatment of heart failure, inotropic agents yield short-term hemodynamic improvement. However, inotropic therapy is still an unfilled promise for the treatment of chronic heart failure (1). This may partly result from the fact that inotropic interventions increase myocardial oxygen consumption (VO2). Therefore, the investigation of myocardial energetics in relation to inotropic agents in patients with heart disease has clinical and therapeutic relevance. Recently, the concept of left ventricular (LV) elastance (Emax) and systolic pressure-volume area (PVA) has been proposed by Suga and his colleagues (2,3,4,5). Experimental studies have shown that the relation between VO2 and PVA is linear under a variety of loading conditions. This linear relation has been used to partition VO2 into non-mechanical and mechanical portions. Experimental studies have shown that positive inotropic interventions, which enhance Emax, shift the VO2-PVA relation line upward in a parallel manner. The resultant increase in VO2 intercept of the relation has been considered to be VO2 for non-mechanical work. The relation between Emax and PVA-independent VO2 has been reported to be linear; the slope represents “oxygen cost of contractility” under various inotropic interventions. The aim of this study was to examine the effects of various inotropic agents on human cardiac mechanoenergetics by utilizing the concept of Emax and the VO2-PVA relation. To this end, we compared the effects of the newly developed phosphodiesterase inhibitor E-1020 and a novel Ca++ sensitizing agent, MCI-154, with dobutamine in patients with heart disease.