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. Ca2+ transient and cell shortening in isolated cardiac myocytes were simultaneously measured using ion imaging system. RESULTS ① MCI-154 100-400 μmol·L-1 improved cardiac performance assessed by active systolic pressure (left ventricular systolic pressure minus left ventricular diastolic pressure) and +dp/dtmax in hypertrophied hearts as well as in normal ones, and -dp/dtmax tended to increase slightly with no statistical significance; ② MCI-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 1, 10 and 100 μmol·L-1, respectively, with unaltered Ca2+ transient amplitude and Ca2+ transient decline assessed by time at 50% and 90% restoring. CONCLUSIONMCI-154 exerted positive inotropic effect concentration dependently via calcium sensitizing on hypertrophied rat heart as on normal rat heart.%目的探讨钙增敏剂MCI-154[6-[4-(4-吡啶氨基)苯基]-4,5-二氢-3(2H)哒嗪酮]对心肌肥厚心脏与对正常心脏的作用是否不同及有关的机制.方法 利用离体心脏灌流技术观察MCI-154对心肌肥厚大鼠心功能的影响;应用离子影像学分析系统同步测定心肌细胞钙浓度瞬变和细胞长度.结果①MCI-154 100～400μmol·L-1范围内浓度依赖性地提高了心肌肥厚大鼠心功能的名项指标.在400μmol·L-1时,左室主动收缩压(左室收缩峰压与左室舒张末压之差)及左室压最大上升速率(+dp/dtmax)与对照值相比显著增加,左室压最大下降速率(-dp/dtmax)有增高趋势,但无统计学意义;②MCI-154 ～100μmol·L-1在钙瞬变无明显改变情况下,呈浓度依赖性增加肥厚心肌细胞的缩短程度和钙敏感性;③MCI-154对肥厚心肌细胞钙瞬变的50％和90％恢复时间影响不大.结论在心肌肥厚大鼠心脏上,和在正常大鼠心脏上一样,MCI-154主要通过钙增敏作用发挥其正性变力作用.
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