M. Diebel1, D. Liberati1, J. Liberati1, L. Diebel1 1Wayne State University,Department Of Surgery/School Of Medicine,Detroit, MI, USA
Introduction: Early adminstration of tranexamic acid (TXA) appears to reduce mortality in bleeding trauma patients. Potential mechanisms include decreased blood loss and antiinflammatory effects with TXA administration. Hemorrhagic shock (HS) related gut ischemia leads to disruption of the mucosal barrier. This has been attributed to entry of activated digestive enzymes into the intestinal wall and subsequent activation of mucosal associated matrix metallopeptidase 9 (MMP-9). Both "systemic" and enteral administration of TXA may protect the gut barrier following HS. The temporal response and mechanism(s) are unknown and served as the basis of the current study.
Methods: Caco-2 (intestinal cells) + HT29-MTX (mucus cells) intestinal epithelial cell (IEC) co cultures were established in a two-chamber cell culture system. IEC co cultures were then exposed to hypoxia-reoxygenation (HR) challenge ± trypsin added to the apical media. TXA was added in some experimental groups immediately after hypoxic challenge (Time 0) and then 60 and 120 minutes following reoxygenation. Trypsin activity was measured using a substrate specific assay (N α-Benzoyl-L-arginine 4-nitroanilide hydrochloride, BAPNA) at times corresponding to 60 minute intervals +/- TXA administration. MMP-9 was determined from intestinal lysates at corresponding times using Western blot analysis and quantified by relative density calculation.
Results: Please see table.
Conclusion: The protective effect of TXA on gut barrier function may be due to inhibition of trypsin and subsequent MMP-9 activation. These effects were noted only with TXA administration within 60 minutes following the 90 minute IEC hypoxic challenge. These results support the early administration of TXA in bleeding trauma patients and may represent an additional benefit of TXA in these patients.
