This study was designed to investigate the effect of a
calcium sensitizer on the Ca2+ sensitivity of myocardial fibers in endotoxic
shock rats. Right ventricular papillary muscles from
sham shock or endotoxic
shock rats were skinned by incubation in
saponin solution. Forces of the skinned muscles were recorded when they were activated sequentially by different pCa (-log[Ca2+]) activating solutions with or without positive inotropic agents. Tension-pCa relationship curve of skinned fibers delineated the affinity of
troponin C(TnC) for Ca2+ and the medium value pCa50 (pCa required for producing 50% of maximal Ca2+-activated tension) was taken as the quantitative index of Ca2+ sensitivity of TNC. It was found that the maximal Ca2+ activated tension (Tmax) was lower, tension-pCa relationship curve was shifted rightward, and the pCa50 was reduced significantly in endotoxic
shock group compared with that of
sham shock group.
Milrinone could not counteract the above abnormalities. However, when skinned right ventricular papillary fibers from endotoxic
shock rats were dealt with activating solutions containing 1 x 10(-5) M
MCI-154, the Tmax was significantly increased, the tension-pCa relationship curve was shifted leftward. The pCa50 in
MCI-154 group was increased to an extent similar to that of
sham shock group and markedly higher than the values of endotoxic
shock group and
milrinone group. Furthermore, such effects of
MCI-154 were concentration dependent. It can been concluded that the sensitivity of cardiac
contractile proteins to Ca2+ in endotoxic
shock rats is decreased.
MCI-154, a
calcium sensitizer, can significantly reverse the decreased sensitivity and increase Tmax of myocardial muscles from endotoxic
shock rats.