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 (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 +/- 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 (delta VO2/delta Emax) 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, delta VO2/delta Emax for 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.
Onishi
K
K
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Sekioka
K
K
Ishisu
R
R
Abe
Y
Y
Tanaka
H
H
Nakamura
M
M
Ueda
Y
Y
Nakano
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D011724:Pyridazines; D011189:Potassium Chloride; C052228:MCI 154; D002118:Calcium