1014-95 Comparative Effect of Inotropic Agents on Oxygen Expenditure Between β-Stimulation, Phospho-Diesterase Inhibition and Ca2+ Sensitization

Abstract

A newly developed cardiotonic agent, MCI-154, increases sensitivity of myofilament to Ca 2+ , which could generate force with less Ca 2+ , and hence potentially save myocardial oxygen consumption (VO 2 ). We compared the effect of MCI-154 (MCI; 16.6 μ g/min, n = 12) on VO 2 to those of dobutamine (Dob; 5 mu;g/kg/min, n = 12) and phospho-diesterase inhibitor, E1020, (PDE-I; 0.3 μ g/kg/min, n = 10) in patients with left ventricular (LV) dysfunction. Inotropic and vasodilative actions were assessed by LV elastance, E max , and effective arterial elastance, E a , by the conductance catheter, and VO 2 by the Webster catheter. Total mechanical energy was assessed by the systolic pressure-volume area (PVA) consisting of external work (EW) and potential energy (PE). VO 2 (VO 2,total ) was divided into PVA-dependent component (VO 2,EW and VO 2,PE ) and PVA-independent component (VO 2,NMW ) used for non-mechanical work (excitation-contraction coupling or Ca 2+ handling). Increases in E max was comparable (Dob; 42 ± 21, PDE-I; 44 ± 13, MCI; 56 ± 34%, ns) but decline in E a was the largest with PDE-I (Dob; 9 ± 37, PDE-I; -19 ± 13 # , MCI; 1 ± 14%, p < 0.05 by ANOVA). ΔVO 2,total ΔVO 2,EW ΔVO 2,PE ΔVO 2,NMW Dob 1.1 ± 0.8 * 0.56 ± 0.64 * -0.3 ± 0.6 0.8 ± 0.8 * PDE-I -0.1 ± 0.7 0.12 ± 0.21 * -0.9 ± 1.2 * 0.7 ± 1.2 * MCI -0.5 ± 0.9 * 0.08 ± 0.37 -0.7 ± 0.7 * 0.1 ± 0.4 mean ± SD in J/beat * p < 0.05 vs corresponding control Dob increased VO 2,total but MCI remained unchanged VO 2,total mainly due to the decline in VO 2,PE . Unlike Dob and PDE-I, MCI did not increase VO 2,NMW , leading to the decreases in VO 2,total , which may result from less VO 2 for non-mechanical work. In conclusion, Ca 2+ sensitizer, MCI-154, saves oxygen expenditure for non-mechanical work different from β -stimulant and PDE inhibitor.