Oxygen-Saving Effect of New Cardiotonic Agent, MCI-154, in Diseased Human Hearts

Objectives. The aim of this study was to examine the left ventricular mechanoenergetic effects of novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Background. Unlike conventional cardiotonic agents, Ca2+ sensitizer that could produce positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. Methods. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vimage2) were measured by conductance (volume) catheter and Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume are (PV [index of left ventricular total mechanical energy]) and Vimage2 were assessed before and after infusion of MCI-154 or dobutamine. The PVA-independent Vimage2 (Vimage2 mainly for excitation-contraction coupling) was assessed as the Vimage2 at zero PVA. Results. Both agents increased Emax comparably (dobutamine: from 3.55 ± 1.10 [mean ± SD] to 5.04 ± 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 ± 1.26 to 5.37 ± 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vimage2 (from 0.22 ± 0.08 to 0.27 ± 0.09 ml O2, p < 0.05) and PVA-independent Vimage2 (from 0.019 ± 0.019 to 0.091 ± 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (ΔPVA-independent Vimage2/ΔEmax) was less with MCI-154 than with dobutamine (0.14 ± 0.18 vs. 1.10 ± 0.80 J/mm Hg per ml per m2, p < 0.05). Conclusions. These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.