Teramura S, Yamakado T, Maeda M, Nakano T
First Department of Internal Medicine, Mie University, Tsu, Japan.
Circulation. 1997 Feb 4;95(3):732-9. doi: 10.1161/01.cir.95.3.732.
MCI-154 is a positive inotropic agent that increases the myofilament response to Ca2+. Whether MCI-154 has beneficial effects on left ventricular dysfunction in chronic heart failure is not known. We examined the effects of MCI-154 on left ventricular systolic and diastolic function in pacing-induced heart failure in dogs.
We studied eight anesthetized dogs before and 2 to 4 weeks after rapid right ventricular pacing. Left cineventriculograms with simultaneous left ventricular pressures (tip manometer) were obtained before and during intravenous administration of MCI-154 (I.O. microgram.kg-1.min-1 for 15 minutes) in the control and heart-failure states. Left ventricular volume dynamics was derived from frame-by-frame (20-ms) analyses of left ventricular angiograms. In heart failure, left ventricular contractility as assessed by shifts of the end-systolic pressure-volume ratio, evaluated by inferior vena cava occlusion, was improved by MCI-154 (+ 1.94 mm Hg/mL, P < .05) to an extent similar to that in the control state (+2.47 mm Hg/mL, P < .05). MCI-154 also accelerated left ventricular relaxation, assessed by the time constant of isovolumic pressure decay (T1/2), in both states. The absolute decrease in T1/2 with MCI-154 in heart failure was significantly greater than in the control state (-8.2 versus -3.1 ms, P < .05). In heart failure, MCI-154 shifted the left ventricular diastolic pressure-volume relation clearly downward, suggesting increased diastolic distensibility.
MCI-154 improved not only left ventricular systolic function but also diastolic relaxation and distensibility in a chronic heart failure model.
MCI - 154是一种正性肌力药物，可增强肌丝对Ca2 +的反应。MCI - 154对慢性心力衰竭患者左心室功能障碍是否具有有益作用尚不清楚。我们研究了MCI - 154对犬起搏诱导性心力衰竭左心室收缩和舒张功能的影响。
我们在8只麻醉犬快速右心室起搏前及起搏后2至4周进行了研究。在对照和心力衰竭状态下，静脉注射MCI - 154（1.0微克·千克-1·分钟-1，持续15分钟）前及注射期间，记录左心室造影电影及同步左心室压力（顶端压力计）。左心室容积动力学通过对左心室血管造影逐帧（20毫秒）分析得出。在心力衰竭状态下，通过下腔静脉闭塞评估的收缩末期压力-容积比变化来评估左心室收缩力，MCI - 154可使其改善（+1.94毫米汞柱/毫升，P <.05），改善程度与对照状态（+2.47毫米汞柱/毫升，P <.05）相似。在两种状态下，MCI - 154均通过等容压力衰减时间常数（T1/2）评估加速左心室舒张。心力衰竭状态下MCI - 154使T1/2的绝对降低幅度显著大于对照状态（-8.2对-3.1毫秒，P <.05）。在心力衰竭状态下，MCI - 154使左心室舒张压-容积关系明显下移，提示舒张顺应性增加。
在慢性心力衰竭模型中，MCI - 154不仅改善了左心室收缩功能，还改善了舒张松弛和顺应性。
