THE ROLE OF ENDOTOXIN IMMUNITY, NEUTROPHIL DEGRANULATION AND CONTACT ACTIVATION IN THE PATHOGENESIS OF POSTOPERATIVE ORGAN DYSFUNCTION

THE ROLE OF ENDOTOXIN IMMUNITY, NEUTROPHIL DEGRANULATION AND CONTACT ACTIVATION IN THE PATHOGENESIS OF POSTOPERATIVE ORGAN DYSFUNCTION
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DOI:
10.1097/00001721-199304060-00016
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发表时间:
1993-12-01
影响因子:
1.1
通讯作者:
MACHIN, SJ
MACHIN, SJ
中科院分区:
医学4区
文献类型:
--
作者:
MYTHEN, MG;BARCLAY, GR;MACHIN, SJ

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肠粘膜低灌注率与大手术后预后不良有关,但其发病机制尚不清楚。在择期大手术中,我们研究了肠粘膜低灌注率、内毒素核心抗体(EndoCAb)、中性粒细胞弹性蛋白酶α-1抗胰酶复合体(NE)和接触系统成分之间的关系。在所研究的26名患者中,16名患者在手术结束时出现肠粘膜低灌注量(phi&lt;7.32);其中4名患者出现多器官衰竭(MOF),3名患者随后死亡。在这组患者中,NE显著升高(P&lt;0.005),接触系统成分(凝血因子XII、抗凝血酶III、前激肽释放酶和C1抑制物;P&lt;0.001)从术前到术后24小时显著降低。10例患者维持肠道粘膜灌注(phi大于或等于7.32),无一例发生危及生命的并发症。在这一组中,NE没有显著增加,尽管接触系统的某些组件有显著降低(P&lt;0.01),但c1-INH水平并没有降低。所有患者的Ig G和Ig M EndoCAb均显着降低(P<0.005),提示暴露于内毒素。然而,维持肠粘膜灌注组在基线和24小时的IgGEndoCAb水平显著高于对照组(P<0.005)。这些数据表明,所有患者都暴露于内毒素,高水平的抗内毒素抗体可能有助于预防内毒素诱导的接触性激活、中性粒细胞脱颗粒和肠粘膜低灌流在大手术期间发生,从而减少术后MOF的发生。
Gut mucosal hypoperfusion is associated with a poor outcome following major surgery but the pathogenetic mechanisms remain poorly understood. We have examined the relationship between gut mucosal hypoperfusion, endotoxin core antibodies (EndoCAb), neutrophil elastase alpha-1 antitrypsin complexes (NE) and components of the contact system during elective major surgery. Of the 26 patients studied 16 developed gut mucosal hypoperfusion (pHi < 7.32) by the end of surgery; of these four developed multiple organ failure (MOF) and three subsequently died. In this group there was a significant rise in NE (P < 0.005) and significant reductions in components of the contact system (factor XII, anithrombin III, prekallikrein and C1-inhibitor; P < 0.001) from immediately before surgery to 24 h later. Ten patients maintained gut mucosal perfusion (pHi greater than or equal to 7.32); none of these developed life threatening complications. In this group there was no significant increase in NE and, although there were significant reductions in some components of the contact system (P < 0.01), levels of C1-INH were not reduced. All patients demonstrated a significant reduction in both IgG and IgM EndoCAbs (P less than or equal to 0.005) indicating exposure to endotoxin. However, the group that maintained gut mucosal perfusion had significantly higher IgG EndoCAb levels at baseline and 24 h (P less than or equal to 0.005). These data suggest that all patients were exposed to endotoxin and that high levels of anti-endotoxin antibodies may contribute to the prevention of endotoxin-induced contact activation, neutrophil degranulation and gut mucosal hypoperfusion occurring during major surgery and thus reduce the likelihood of the development of post-operative MOF.