Positive Inotropic Effect of MCI-154 on Hypertrophied Heart of Rats and Its Mechanisms

AIM To explore if there is a differential effect of MCI-154〔6-[4-(4'-pyridylamino) phenyl]-4, 5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate〕, a calcium sensitizer, on hypertrophied hearts compared with normal hearts and the possible mechanisms underlying it. METHODS Functions of rat hypertrophied heart were investigated using Langendorff perfusion. Ca(superscript 2+) transient and cell shortening in isolated cardiac myocytes were simultaneously measured using ion imaging system. RESULTS ①MCI-154 100-400μmol•L^(-1) improved cardiac performance assessed by active systolic pressure (left ventricular systolic pressure minus left ventricular diastolic pressure) and +dp/dt(subscript max) in hypertrophied hearts as well as in normal ones, and-dp/dt(subscript max), tended to increase slightly with no statistical significance; ②MCI-154 concentration-dependently increased cell shortening in hypertrophied myocytes from (4.8 ± 1.7)μm of control to (5.6±1.5), (7.6±1.7) and (10.9±1.7)μm at l, 10 and 100μmol•L^(-1), respectively, with unaltered Ca(superscript 2+) transient amplitude and Ca(superscript 2+) transient decline assessed by time at 50% and 90% restoring. CONCLUSION MCI-154 exerted positive inotropic effect concentration dependently via calcium sensitizing on hypertrophied rat heart as on normal rat heart.