Danner R L, Natanson C, Elin R J, Hosseini J M, Banks S, MacVittie T J, Parrillo J E
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Md 20892.
Chest. 1990 Dec;98(6):1480-7. doi: 10.1378/chest.98.6.1480.
We investigated the effects of two different Gram-negative bacteria and radiation-induced leukopenia on endotoxemia, cardiovascular abnormalities, and mortality in a canine model of septic shock. Serial hemodynamics were measured in conscious dogs using radionuclide heart scans and thermodilution cardiac output catheters. Plasma endotoxin concentrations were determined with a chromogenic Limulus amebocyte lysate assay. Viable Pseudomonas aeruginosa or Escherichia coli implanted intraperitoneally produced concordant hemodynamic patterns of septic shock (p less than 0.01). Endotoxin concentrations were more than tenfold lower in dogs infected with P aeruginosa compared with E coli (p less than 0.0001). Despite lower endotoxin levels, P aeruginosa-infected dogs had a higher mortality (p less than 0.01), more severe hypotension (p less than 0.05), and greater depression of the left ventricular ejection fraction (p less than 0.05) than dogs with E coli sepsis. A nonlethal E coli challenge combined with leukopenia (induced by a nonlethal dose of radiation) resulted in a mortality of 60 percent (p less than 0.01) without greater cardiovascular dysfunction or higher endotoxin concentrations. These findings suggest that bacterial products other than endotoxin and host-related factors may be important contributors to the toxicity, cardiovascular instability, and mortality of Gram-negative septic shock. Quantitative determinations of plasma endotoxin are unlikely to correlate with the clinical severity of septicemia in heterogeneous patient populations infected with different Gram-negative organisms.
我们在犬类脓毒症休克模型中研究了两种不同的革兰氏阴性菌以及辐射诱导的白细胞减少对内毒素血症、心血管异常和死亡率的影响。使用放射性核素心脏扫描和热稀释心输出量导管对清醒犬进行连续血流动力学测量。采用显色鲎试剂法测定血浆内毒素浓度。腹腔内植入活的铜绿假单胞菌或大肠杆菌可产生脓毒症休克一致的血流动力学模式(p<0.01)。与感染大肠杆菌的犬相比,感染铜绿假单胞菌的犬内毒素浓度低十倍以上(p<0.0001)。尽管内毒素水平较低,但与大肠杆菌脓毒症犬相比,感染铜绿假单胞菌的犬死亡率更高(p<0.01),低血压更严重(p<0.05),左心室射血分数降低更明显(p<0.05)。非致死剂量的大肠杆菌攻击联合白细胞减少(由非致死剂量辐射诱导)导致死亡率为60%(p<0.01),且无更严重的心血管功能障碍或更高的内毒素浓度。这些发现表明,除内毒素和宿主相关因素外,细菌产物可能是革兰氏阴性菌脓毒症休克毒性、心血管不稳定和死亡率的重要促成因素。在感染不同革兰氏阴性菌的异质患者群体中,血浆内毒素的定量测定不太可能与败血症的临床严重程度相关。