MCI-154, a Ca21 sensitizer, decreases the oxygen cost of contractility in isolated canine hearts

Onishi, Katsuya, Kiyotsugu Sekioka, Ryoichi Ishisu, Yuji Abe, Hideyuki Tanaka, Mashio Nakamura, Yuji Ueda, and Takeshi Nakano. MCI-154, a Ca21 sensitizer, decreases the oxygen cost of contractility in isolated canine hearts. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H1688– H1695, 1997.—An increase in the responsiveness of the contractile machinery to Ca21 could theoretically enhance the mechanoenergetics of the heart. To clarify this unresolved issue, we studied the effects of MCI-154, a Ca21 sensitizer, on the mechanoenergetics in terms of the left ventricular contractility index [slope of end-systolic pressure-volume relationship (Emax)] and the relationship between myocardial oxygen consumption (VO2) and left ventricular pressure-volume area in excised cross-circulated canine hearts. MCI-154 increased Emax by 42 6 31% (SD), although the slope of the VO2-PVA relationship (an indicator of contractile efficiency) was unchanged by MCI-154. Despite equal increases in Emax, the relative increase in unloaded VO2 (DVO2/DEmax) during infusion of MCI-154 was, however, significantly less than that during CaCl2 infusion (0.0016 6 0.0018 vs. 0.0059 6 0.0054; P , 0.05). By contrast, DVO2/DEmax for milrinone was the same as that for CaCl2 (0.0043 6 0.0041 vs. 0.0039 6 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 Ca21 sensitizer in beating canine whole hearts.