MCI-154对心肌肥厚大鼠离体心脏的正性变力作用及其机制(英文)  

Positive inotropic effect of MCI-154 on hypertrophied heart of rats and its mechanisms

作　　者：陈还珍[1] 崔香丽[2] 郭文玲[1] 赵画晨[2] 赵录英[2] 吕吉元[1] 吴博威[2] 

机构地区：[1]山西医科大学第一临床医学院心内科 [2]山西医科大学生理学教研室,山西太原030001

出　　处：《中国药理学与毒理学杂志》2004年第5期338-343,共6页Chinese Journal of Pharmacology and Toxicology

摘　　要：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。AIM To explore if there is a differential effect of MCI-154 〔 6-[4-(4′-pyridylamino) phenyl]-4,5-dihydro-3(2H)-pyridazin one hydrochl oride 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 2+ transient and cell shortening in isolated cardiac myocyte s were simultaneously measured using ion imaging system. RESULTS ① MCI-154 100-400 μmol·L -1 improved cardiac performance assessed by acti ve systolic pressure (left ventricular systolic pressure minus left ventricular diastolic pressure) and +dp/dt max in hypertrophied hearts as well as in normal ones, and -dp/dt max tended to increase slightly with no statistical significance; ② MCI-154 co ncentration-dependently increased cell shortening in hypertrophied myocytes fro m (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 Ca 2+ transient a mplitude and Ca 2+ transient decline assessed by time at 50% and 90% restor ing. CONCLUSION MCI-154 exerted positive inotropic effect concen tration dependently via calcium sensitizing on hypertrophied rat hea rt as on normal rat heart.

关 键 词：钙增敏剂 MCI-154 心脏肥厚 心脏收缩 钙 细胞内 

分 类 号：R96[医药卫生—药理学]