Effect of MCI-154, a calcium sensitizer, on calcium sensitivity of myocardial fibers in endotoxic shock rats

• Published in: Shock (Augusta, Ga.) Ga.), 2000-12, Vol.14 (6), p.652-656
• Main Authors: Ming, M J, Hu, D, Chen, H S, Liu, L M, Nan, X, Hua, C H, Lu, R Q
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Calcium - metabolism; Calcium - pharmacology; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Dose-Response Relationship, Drug; Drug Resistance; Emergency and intensive care: infection, septic shock; Female; In Vitro Techniques; Intensive care medicine; Male; Medical sciences; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - physiology; Myocardial Contraction - drug effects; Papillary Muscles - drug effects; Papillary Muscles - physiopathology; Pyridazines - administration & dosage; Pyridazines - pharmacology; Rats; Rats, Wistar; Shock, Septic - drug therapy; Shock, Septic - physiopathology; Troponin C - metabolism
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/00024382-200014060-00014

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.