钙敏化剂MCI - 154对内毒素血症大鼠心肌收缩系统钙敏感性的影响。

Effect of MCI-154, a calcium sensitizer, on calcium sensitivity of myocardial contractile system in endotoxemic rats.

作者信息

Mei J M, Hu D Y, Chen H S, Liu L M, Xiao N, Chen H H, Lu R Q

机构信息

Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

出版信息

Acta Pharmacol Sin. 2000 Sep;21(9):830-4.

PMID:11501166

Abstract

AIM

To investigate the effect of MCI-154 on calcium sensitivity of myocardial contractile system in endotoxemic rats.

METHODS

Skinned right ventricular papillary muscles from endotoxemic rats were prepared by saponin 500 mg/L. Forces of the skinned muscles were recorded when they were activated sequentially by different concentrations of Ca2+ with or without cardiotonic agents. The tension-pCa relationship and pCa50 of the skinned fibers were taken as the index of Ca2+ sensitivity of myocardial contractile system.

RESULTS

The maximal Ca(2+)-activated tension (Tmax) was lower, and pCa50 was reduced in endotoxemia group as compared with those in sham control group. Milrinone 50 mumol/L could not counteract the above abnormalities. However, after MCI-154 10 mumol/L was added, the Tmax and pCa50 were increased to an extent similar to that of sham control group and significantly higher than those of endotoxemia group and endotoxemia + milrinone group. Furthermore, such effects of MCI-154 were concentration-dependent.

CONCLUSION

The Ca2+ sensitivity of cardiac contractile system in endotoxemic rats is decreased. MCI-154 can reverse the decreased sensitivity and increase Tmax of myocardial muscles from endotoxemic rats.

摘要

目的

研究MCI - 154对内毒素血症大鼠心肌收缩系统钙敏感性的影响。

方法

用500mg/L皂苷制备内毒素血症大鼠的去表皮右心室乳头肌。在有或无强心剂存在的情况下，用不同浓度的Ca2+依次激活去表皮肌肉，记录其力量。将去表皮纤维的张力 - pCa关系和pCa50作为心肌收缩系统Ca2+敏感性的指标。

结果

与假手术对照组相比，内毒素血症组的最大Ca(2+)激活张力（Tmax）较低，pCa50降低。50μmol/L米力农不能抵消上述异常。然而，加入10μmol/L MCI - 154后，Tmax和pCa50升高至与假手术对照组相似的程度，且显著高于内毒素血症组和内毒素血症 + 米力农组。此外，MCI - 154的这种作用呈浓度依赖性。