Rigby S L, Hofmann P A, Zhong J, Adams H R, Rubin L J
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211, USA.
Am J Physiol. 1998 Feb;274(2):H580-90. doi: 10.1152/ajpheart.1998.274.2.H580.
Myocardial contractile function is depressed after onset of endotoxemia and is intrinsic to the ventricular myocyte. We tested the hypothesis that decreased Ca2+ responsiveness of the contractile myofilaments underlies this inotropic depression. Specifically, we evaluated the relationship between Ca2+ and unloaded cell shortening and isometric tension development of skinned guinea pig ventricular myocytes. Myocytes were isolated 4 h after intraperitoneal injection of 4 mg/kg Escherichia coli lipopolysaccharide (LPS) or saline (control; Ctl). Myofilament Ca2+ responsiveness assessed by image analysis of shortening of skinned myocytes at pH 7.0 was not different between Ctl[pCa value that resulted in half-maximal shortening (pCa50): 5.78 +/- 0.04] and LPS (pCa50: 5.72 +/- 0.02). Similarly, myofilament Ca2+ responsiveness measured by isometric tension of skinned myocytes was not different between Ctl (pCa50: 5.73 +/- 0.02) and LPS (pCa50: 5.76 +/- 0.02). Maximal tension generated by LPS myocytes (2.89 +/- 0.23 g/mm2) was significantly less (P < 0.05) than Ctl (3.75 +/- 0.34 g/mm2). However, when myocytes were isolated and skinned in the presence of protease inhibitors, maximal tension generated by LPS myocytes (3.53 +/- 0.98 g/mm2) was similar to Ctl (3.01 +/- 0.80 g/mm2). We conclude that in vivo administration of LPS resulting in endotoxemia without shock does not alter myofilament Ca2+ responsiveness of ventricular myocytes. Rather, reduced contractility is more likely a result of decreased Ca2+ availability because systolic Ca2+ transients of fura 2-loaded LPS myocytes were significantly decreased (P < 0.05) compared with Ctl myocytes.
内毒素血症发作后心肌收缩功能降低，且这种降低是心室肌细胞所固有的。我们检验了这样一个假说，即收缩性肌丝对钙离子反应性降低是这种变力性降低的基础。具体而言，我们评估了钙离子与去表皮豚鼠心室肌细胞无负荷细胞缩短及等长张力发展之间的关系。在腹腔注射4mg/kg大肠杆菌脂多糖（LPS）或生理盐水（对照；Ctl）4小时后分离心肌细胞。通过对pH7.0下去表皮心肌细胞缩短的图像分析评估的肌丝钙离子反应性，在Ctl组[导致最大缩短一半时的钙离子浓度值（pCa50）：5.78±0.04]和LPS组（pCa50：5.72±0.02）之间没有差异。同样，通过去表皮心肌细胞的等长张力测量的肌丝钙离子反应性，在Ctl组（pCa50：5.73±0.02）和LPS组（pCa50：5.76±0.02）之间也没有差异。LPS处理的心肌细胞产生的最大张力（2.89±0.23g/mm2）明显低于（P<0.05）Ctl组（3.75±0.34g/mm2）。然而，当在蛋白酶抑制剂存在的情况下分离并去表皮心肌细胞时，LPS处理的心肌细胞产生的最大张力（3.53±0.98g/mm2）与Ctl组（3.01±0.80g/mm2）相似。我们得出结论，在体内给予LPS导致无休克的内毒素血症不会改变心室肌细胞的肌丝钙离子反应性。相反，收缩性降低更可能是由于钙离子可用性降低所致，因为与Ctl组心肌细胞相比，用fura 2标记的LPS处理的心肌细胞的收缩期钙离子瞬变明显降低（P<0.05）。
