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

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.