Effect of Inotropic Agents on Mechanoenergetics in Human Diseased Heart

Abstract

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 (E_max) 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 E_max, 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 E_max 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 E_max 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.