Goddard C M, Allard M F, Hogg J C, Walley K R
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Am J Physiol. 1996 Apr;270(4 Pt 2):H1446-52. doi: 10.1152/ajpheart.1996.270.4.H1446.
Decreased ventricular contractility during sepsis lasts much longer than the half-lives of inflammatory mediators that have been suggested to be myocardial depressant factors. Our hypothesis is that blood-borne factors may also cause myocardial structural changes, including damage and death of myocytes, associated with decreased ventricular contractility. We tested this hypothesis in an isolated rabbit heart perfused by a support rabbit. Support rabbits received 1 mg/kg endotoxin i.v. over 30 min (endotoxin group, n = 7) or vehicle (control group, n = 6). The slope of the end-systolic pressure-volume relationship, Emax, was used to measure contractility of the isolated heart. Five hours after endotoxin infusion, Emax decreased by 17 +/- 7% (P < 0.03) compared with 0 +/- 2% in the control group. Quantitative morphometric analysis of isolated hearts from the endotoxin group demonstrated an increased volume fraction of myocardial capillaries occupied by leukocytes (15.7 +/- 3.5 vs. 3.0 +/- 0.7% in the control group, P < 0.05), structurally abnormal myocytes (7.6 +/- 3.6 vs. 0.8 +/- 0.4%, P < 0.05), and interstitial edema (23.2 +/- 5.2 vs. 14.3 +/- 2.1%, P < 0.05). We conclude that blood-borne factors cause myocardial structural changes that may contribute to decreased ventricular contractility and may explain the prolonged decrease in ventricular contractility during sepsis.
脓毒症期间心室收缩力下降持续的时间远长于那些被认为是心肌抑制因子的炎症介质的半衰期。我们的假设是，血源性因子也可能导致心肌结构改变，包括心肌细胞损伤和死亡，进而导致心室收缩力下降。我们在由供血兔灌注的离体兔心脏中验证了这一假设。供血兔静脉注射1 mg/kg内毒素，持续30分钟（内毒素组，n = 7）或注射溶媒（对照组，n = 6）。用收缩末期压力-容积关系斜率（Emax）来测量离体心脏的收缩力。内毒素输注5小时后，Emax下降了17±7%（P < 0.03），而对照组为0±2%。对内毒素组离体心脏进行的定量形态学分析显示，被白细胞占据的心肌毛细血管容积分数增加（15.7±3.5%对对照组的3.0±0.7%，P < 0.05），心肌细胞结构异常（7.6±3.6%对0.8±0.4%，P < 0.05），以及间质水肿（23.2±5.2%对14.3±2.1%，P < 0.05）。我们得出结论，血源性因子会导致心肌结构改变，这可能会导致心室收缩力下降，并可能解释脓毒症期间心室收缩力下降时间延长的原因。
