MCI-154, a Ca2+ sensitizer, decreases the oxygen cost of contractility in isolated canine hearts.

An increase in the responsiveness of the contractile machinery to Ca2+could theoretically enhance the mechanoenergetics of the heart. To clarify this unresolved issue, we studied the effects of MCI-154, a Ca2+ sensitizer, on the mechanoenergetics in terms of the left ventricular contractility index [slope of end-systolic pressure-volume relationship ( E max)] and the relationship between myocardial oxygen consumption (Vo 2) and left ventricular pressure-volume area in excised cross-circulated canine hearts. MCI-154 increased E max by 42 ± 31% (SD), although the slope of the Vo 2-PVA relationship (an indicator of contractile efficiency) was unchanged by MCI-154. Despite equal increases in E max, the relative increase in unloaded Vo 2(ΔVo 2/Δ E max) during infusion of MCI-154 was, however, significantly less than that during CaCl2 infusion (0.0016 ± 0.0018 vs. 0.0059 ± 0.0054; P < 0.05). By contrast, ΔVo 2/Δ E maxfor milrinone was the same as that for CaCl2 (0.0043 ± 0.0041 vs. 0.0039 ± 0.0045; P > 0.05). Basal metabolism in KCl-arrested hearts was unchanged by MCI-154, indicating that MCI-154 consumes less energy than CaCl2 for excitation-contraction coupling. These findings suggest that MCI-154 acts energetically as a Ca2+ sensitizer in beating canine whole hearts.