Uemura A, Dabasaki T, Notsu T, Yamasaki F, Nakakuki M, Shinkawa T, Kosuzume H, Okada K
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Circ Shock. 1989 Mar;27(3):173-82.
To elucidate the mechanisms of protective effect of M6434 on experimental shock, the authors examined the effects of this compound on the survival time and hemodynamic changes in severely hemorrhagic-shocked dogs. We also examined the effects of M6434 on contractile tension of isolated canine ventricular strips and on venous return in dogs with cardiopulmonary bypass in normal and shock state. Intravenous infusion of M6434 at 10 micrograms/kg/min prolonged survival and maintained mean arterial pressure, cardiac output, and first derivative of left ventricular pressure at higher levels than those in the control group, whereas dopamine (10 micrograms/kg/min) did not significantly affect survival time and hemodynamic parameters. M6434 did not change contractile tension in electrically stimulated canine ventricular strips. M6434 (20 micrograms/kg/min) increased the venous return of dogs with cardiopulmonary bypass in both shock and normal state. Phenylephrine (20 micrograms/kg/min) slightly increased venous return in normal state, but not during shock. Dopamine had no effect at 20 micrograms/kg/min, but it increased venous return in both states at 50 micrograms/kg/min. These results suggest that M6434 may improve the hemodynamic derangement in severe hemorrhagic shock through decreasing venous blood pooling.
为阐明M6434对实验性休克的保护作用机制，作者研究了该化合物对严重失血性休克犬的存活时间和血流动力学变化的影响。我们还研究了M6434对正常和休克状态下体外循环犬离体心室肌条收缩张力及静脉回流量的影响。以10微克/千克/分钟的速度静脉输注M6434可延长存活时间，并使平均动脉压、心输出量和左心室压力的一阶导数维持在高于对照组的水平，而多巴胺（10微克/千克/分钟）对存活时间和血流动力学参数无显著影响。M6434对电刺激的犬心室肌条的收缩张力没有影响。M6434（20微克/千克/分钟）可增加休克和正常状态下体外循环犬的静脉回流量。去氧肾上腺素（20微克/千克/分钟）在正常状态下可使静脉回流量略有增加，但在休克时则无此作用。多巴胺在20微克/千克/分钟时无作用，但在50微克/千克/分钟时可增加两种状态下的静脉回流量。这些结果表明，M6434可能通过减少静脉血液淤积来改善严重失血性休克时的血流动力学紊乱。
