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目的 探讨钙增敏剂MCI 15 4〔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 15 4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 15 410 0～ 4 0 0 μmol·L- 1范围内浓度依赖性地提高了心肌肥厚大鼠心功能的各项指标。在 4 0 0μmol·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 15 410～ 10 0 μmol·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 15 4对肥厚心肌细胞钙瞬变的 5 0 %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 15 4主要通过钙增敏作用发挥其正性变力作用。
Objective To investigate the effects of calcium sensitizer MCI154 〔6 [4 (4-pyridinylamino) phenyl] -4,5 dihydro2 (3H) pyridazinone on cardiac hypertrophy and normal heart and its mechanism . Methods The effects of MCI154 on cardiac function in hypertrophic cardiomyocytes were observed by means of isolated cardioplegia. Synchronous determination of calcium concentration transient and cell length in cardiomyocytes was performed by ion imaging analysis system. Results ①MCI 15 410 0 ~ 400 μmol·L -1 concentration-dependently increased cardiac hypertrophy rat heart function of the indicators. Left ventricular active systolic pressure (difference between left ventricular systolic pressure and left ventricular end-diastolic pressure) and maximum rate of left ventricular pressure (+ dp / dtmax) increased significantly at 400 μmol·L-1 compared with the control (-dp / dtmax), but there was no statistical significance. (2) MCI 15 410 ~ 10 0 μmol·L-1 showed a concentration-dependent increase in hypertrophy with no significant changes in calcium transients The extent of myocardial cell shortening and calcium sensitivity; ③ MCI 15 4 has no effect on the 50% and 90% recovery time of calcium transients in hypertrophic cardiomyocytes. Conclusions MCI 15 4 exerts its positive inotropic effect primarily on calcium sensitization in the heart of hypertrophied rats, as in normal rat hearts.