钙增敏剂MCI-154对内毒素休克大鼠心肌钙敏感性的影响

Effects of calcium sensitizer on myocardial calcium sensitivity during endotoxic shock in rats

目的研究钙增敏剂对内毒素休克大鼠心肌钙敏感性的影响。方法利用皂素溶液浸浴假休克或内毒素休克大鼠右心室乳头肌 ,制备裸露心肌纤维标本 ,用不同pCa( -log[Ca2 + ])的含或不含强心药物的激活液进行顺序激活 ,记录Ca2 + 激活张力。结果同假休克组相比 ,内毒素休克大鼠裸露乳头肌钙最大激活张力(Tmax)明显降低 ,张力 pCa曲线向右移位 ,曲线中位值pCa50(产生50 %Tmax 所对应的pCa)降低。甲腈吡酮对上述异常无明显的纠正作用。内毒素休克大鼠裸露乳头肌经含1×10-5 mol/L的MCI 154的激活液处理后 ,Tmax 明显增加 ,张力 pCa曲线向左移位 ,pCa50 值增加 ,明显高于内毒素休克组和Milrinone组值 ,接近假休克组值。MCI 154的上述作用还具有剂量依赖性。结论大鼠内毒素休克后 ,心肌收缩蛋白对钙的敏感性降低 ,MCI 154可明显增加内毒素休克大鼠心肌收缩蛋白对钙的敏感性 ,增加心肌钙最大激活张力。

Objective To study the effects of calcium sensitizer MCI-154 on myocardial sensitivity to calcium during endotoxic shock in rats. Methods Papillary muscle of the right venticle of rats with sham shock or endotoxic shock was incubated in saponin solution to prepare the specimen of naked myocardial fibers. The tension of naked myocardial fibers was recorded after they were activated sequentially with different pCa(-log ) activating solutions with or without cardiotonic agents. Results The maximal activated tension (Tmax) of the naked fibers of papillary muscle was significantly lower in the rats with endotoxic shock than in those with sham shock. The curve of Tmax-pCa relationship was shifted rightward. pCa50 of the curve (the value of pCa to produce 50% Tmax) was reduced in the endotoxic group. Milrinone was unable to correct the above abnormalities. When the naked fibers of the papillary muscle of the rats with endotoxic shock were treated with the activating solution containing 10-5 mol/L NCI-154, the Tmax was significantly increased and the Tmax-pCa relationship curve was shifted leftward. And the value of pCa50 was increased correspondingly approaching to that of the sham shock group. Such effect of MCI-154 was concentration-dependent. Conclusion The sensitivity o myocardial contractile protein to calcium is decreased in the rats with endotoxic rats. MCI-154, a calcium sensitizer, is able to reverse the decreased sensitivity significantly and increase the Tmax of the myocardium.