Study on the mechanical analysis of septic shock and its theraputic strategy

冲击机理分析。我们重新评估了在感染性休克中起主要作用的TNF/Cachectin。我们重新检查重组TNF（Dai Nippon Phamaco.）的休克作用。Cerami在同一模型中重新采用了这种方法。这种TNF在大鼠体内不诱导休克状态。该TNF含有的内毒素（20 μ g/g TNF）比Cerami使用的TNF（0.4 μ g/mg TNF）低得多。但我们的TNF + LPS给药可导致大鼠进入休克状态。由此可见，少量LPS和TNF的作用比单独作用强。同样，我们重新研究了休克诱发剂之一的白细胞毒素（Ozawa报道）。将合成的白细胞毒素注射到大鼠体内。他们死于严重肺出血，无低血压。他们的死亡被认为是由施瓦茨曼反应引起的。这些结果表明TNF或白细胞毒素不是导致感染性休克的主要物质。我们正在对IL-1进行进一步的研究。通过PMX-F或蛋白酶抑制剂（乌司他丁）治疗犬感染性休克。我们对E.大肠杆菌引起的感染性休克PMX-F治疗延长了存活时间（对照组; 18小时<，治疗组; 3-7天>）。PMX-F治疗组的各种参数（主要是细菌计数、血清葡萄糖水平）改善。我们通过使用乌司他丁代替PMX-F进行了相同的上述实验。通过这种治疗，犬的生存时间延长，心输出量，低血压，RES功能本身得到改善。

Analysis of shock mecanism. We re-evaluate the TNF/Cachectin which plays a main role in septic shock. We re-examine the shock-action of recombinant TNF (Dai Nippon Phamaco.). This method has been re-employed in the same model by Cerami. This kind of TNF does not induce the shock state in the rat. This TNF containd much less endotoxin ( 20 pg-LPS/g-TNF ) than TNF (0.4mu/mg-TNF) used by Cerami. But our TNF plus LPS administration could lead the rat into the shock state. According to this results, small amount of LPS and TNF act more stronger than each one. Simillary we re-studied leukotoxin (reported by Ozawa) which is one of the shock-inducing madiator. Synthetic leucotoxin was injected into rat. They died in a result of severe lung hemorrhage without hypotension. Their death is concidered to be caused by shwartzman reaction. These results indicate that TNF or Leukotoxin does not play a main substance leading to septic shock. We are now performing further study on IL-1. Treatment of septic shock in the dog by PMX-F or protease inhibitor (Urinastatin). We performed the PMX-F treatment for the E. coli-induced septic shock. PMX-F treatment prolonged the survival time (Control group; 18 hr<,Treated group; 3-7 days>). Various parameters (mainly bacterial counts, serum-glucose level) improving in the PMX-F treatment group. We performed the same above mentioned experiment by using urinastatin instead of PMX-F. By this treatment, canine was prolonged survival time and improved cardiac output, hypotension, RES-function itself.