Inducible nitric oxide synthase upregulates tissue factor in trauma and shock

Vaishali D. Schuchert*, Melina R. Kibbe, Susan L. Gleixner, Timothy R. Billiar, Brian G. Harbrecht, Satish C. Muluk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Hy-percoagulable states induced by trauma and hemorrhagic shock (HS) can lead to microcirculatory organ failure. Tissue Factor (TF), the main initiator of the coagulation cascade, has been implicated in post-ischemia reperfusion injury. Inhibition of inducible nitric oxide synthase (iNOS) has been shown to at-tenuate organ injury in HS. We hypothesized that iNOS upregulates TF activity in trauma and HS. Methods: iNOS knockout (iNOS KO) mice and their counterpart wild types (WT) underwent laparotomy, hemorrhage, and resuscitation. Control animals did not undergo any manipulations. Functional lung and aortic TF activity was measured via chromogenic assay. Results: There were no significant differences in lung or aortic TF activity among WT and iNOS KO controls or between WT control and WT shock groups. However, lung TF activity was significantly less in iNOS KO shock mice compared to iNOS KO controls (p=0.028, ANOVA). Aortic TF activity in shocked iNOS KO mice was significantly less compared to WT controls (p=0.015), iNOS KO controls (p=0.001), and WT shock mice (p=0.038) (Figure). Conclusions: This is the first report of NO's regulatory role of TF in trauma and HS. We conclude that iNOS upregulates TF in lung and aorta in trauma and HS. Further delineation of the interactions between NO and TF could result in novel therapies for the management of multiply injured patients.

Original languageEnglish (US)
Pages (from-to)A24
JournalCritical care medicine
Volume27
Issue number12 SUPPL.
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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