Takeuchi K, del Nido P J, Ibrahim A E, Poutias D N, Glynn P, Cao-Danh H, Cowan D B, McGowan F X
Department of Anesthesiology, Harvard Medical School, Boston, Mass., USA.
Surgery. 1999 Aug;126(2):231-8.
Mechanisms of cardiac dysfunction during endotoxemia are multiple and their targets uncertain. This study tested the hypothesis that endotoxin (LPS) induces abnormal calcium-activated contractile force in the heart.
Adult rabbits were given LPS intravenously; 2 hours later hearts were studied in the Langendorff mode. Measurements included peak developed pressure (PDP), myocardial oxygen consumption (MVO2), high-energy phosphates by 31P-NMR, and beat-to-beat intracellular calcium (Cai) by fluorescence spectroscopy. Myofibrillar calcium sensitivity was assessed from the relationship of PDP to Cai and the rate of diastolic Cai removal (tau Ca) was quantified.
Force-calcium relationships were markedly depressed in LPS hearts despite increased Cai. MVO2 was increased in parallel with increased Cai. Taken together, these data denote myofilament calcium insensitivity and mechanical inefficiency. tau Ca was markedly prolonged in LPS hearts, indicating impaired calcium reuptake and/or extrusion. High-energy phosphates and intracellular pH were unaffected by LPS; however, inorganic phosphate (Pi) was significantly increased. Dobutamine further increased Cai and MVO2 in LPS hearts without significantly improving calcium-activated force. Pyruvate, an inotrope that reduces Pi, significantly improved contractility in LPS hearts.
Endotoxemia rapidly induced futile calcium cycling and reduced myofibrillar calcium sensitivity. This state was resistant to beta-agonist inotropic stimulation; inotropes that normalize the calcium-force relationship may be more effective.
内毒素血症期间心脏功能障碍的机制是多方面的，其靶点尚不确定。本研究检验了内毒素（脂多糖）在心脏中诱导异常钙激活收缩力的假说。
成年兔静脉注射脂多糖；2小时后在Langendorff模式下研究心脏。测量指标包括最大发展压力（PDP）、心肌耗氧量（MVO2）、通过31P-NMR检测的高能磷酸盐以及通过荧光光谱法检测的逐搏细胞内钙（Cai）。根据PDP与Cai的关系评估肌原纤维钙敏感性，并对舒张期Cai清除率（tau Ca）进行量化。
尽管Cai增加，但脂多糖处理的心脏中力-钙关系明显降低。MVO2与Cai增加同时升高。综合来看，这些数据表明肌丝钙不敏感和机械效率低下。脂多糖处理的心脏中tau Ca明显延长，表明钙再摄取和/或外排受损。高能磷酸盐和细胞内pH不受脂多糖影响；然而，无机磷酸盐（Pi）显著增加。多巴酚丁胺进一步增加了脂多糖处理的心脏中的Cai和MVO2，但未显著改善钙激活力。丙酮酸是一种可降低Pi的正性肌力药物，可显著改善脂多糖处理的心脏的收缩力。
内毒素血症迅速诱导无效的钙循环并降低肌原纤维钙敏感性。这种状态对β受体激动剂正性肌力刺激有抵抗性；使钙-力关系正常化的正性肌力药物可能更有效。
