Siebeck M, Fink E, Weipert J, Jochum M, Fritz H, Spannagl M, Kroworsch P, Shimamoto K, Schweiberer L
Department of Surgery, University of Munich, Klinikum Innenstadt, Federal Republic of Germany.
J Trauma. 1993 Feb;34(2):193-8. doi: 10.1097/00005373-199302000-00002.
Activation of the contact phase of coagulation has been implicated in the pathogenesis of septic shock. We wanted to determine if inhibition of plasma kallikrein can prevent arterial hypotension and liberation of kinins from kininogen, induced by an infusion of bacterial lipopolysaccharide (LPS) in anesthetized, ventilated 20-kg pigs. The LPS was given IV in a dose of 5 micrograms/kg/h for 8 hours. The plasma kallikrein inhibitor aprotinin, 537 mumol, was given IV during 8 hours, resulting in plasma levels above 10 mumol/L. Ten animals (SA) received LPS and aprotinin and ten randomized controls (SC) received LPS and saline. Kinin-containing kininogen was determined on the basis of the amount of kinin releasable in plasma samples by incubation with trypsin. Kininogen decreased to 58% +/- 4% of the baseline value without any difference between groups. This may indicate participation of other processes than degradation by plasma kallikrein in the decrease of kininogen. Arterial blood pressure was higher at 7 hours in the SA animals than in the SC group (101% +/- 11% vs. 68% +/- 8%; mean +/- SEM; p = 0.026). Fibrin monomer and C3adesArg plasma levels were attenuated by aprotinin treatment. These findings underscore the important role of the contact system in LPS shock.
凝血接触相的激活与感染性休克的发病机制有关。我们想确定抑制血浆激肽释放酶是否能预防麻醉通气的20千克猪输注细菌脂多糖（LPS）诱导的动脉低血压和激肽从激肽原的释放。以5微克/千克/小时的剂量静脉注射LPS，持续8小时。在8小时内静脉注射537微摩尔的血浆激肽释放酶抑制剂抑肽酶，使血浆水平高于10微摩尔/升。十只动物（SA组）接受LPS和抑肽酶，十只随机对照动物（SC组）接受LPS和生理盐水。基于血浆样品与胰蛋白酶孵育时可释放的激肽量来测定含激肽的激肽原。激肽原降至基线值的58%±4%，两组之间无差异。这可能表明除了血浆激肽释放酶降解外，其他过程也参与了激肽原的减少。SA组动物在7小时时的动脉血压高于SC组（101%±11%对68%±8%；均值±标准误；p = 0.026）。抑肽酶治疗使纤维蛋白单体和C3adesArg血浆水平降低。这些发现强调了接触系统在LPS休克中的重要作用。
