Date on Master's Thesis/Doctoral Dissertation

12-2020

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Smith, Jason

Committee Co-Chair (if applicable)

Maldonado, Claudio

Committee Member

Maldonado, Claudio

Committee Member

Metz, Cynthia

Committee Member

D'Souza, Stanley

Committee Member

Harbrecht, Brian

Author's Keywords

physiology; hemorrhagic shock; resuscitation; intestinal barrier; trauma; microcirculation

Abstract

Background: Intestinal ischemia-reperfusion injury (IIRI) following resuscitated hemorrhagic shock (HS/RES) leads to endothelial damage, microcirculatory dysfunction and intestinal barrier breakdown, increasing intestinal permeability. This pathologic process contributes pathophysiology of multiple organ dysfunction syndrome (MODS) in some trauma patients. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell damage, resulting in further ischemia and organ injury. Used separately, resuscitation with Fresh Frozen Plasma (FFP) or Direct Peritoneal Resuscitation (DPR) improves the intestinal microcirculation and alleviates organ injury. Further examination of these effects individually or combined could aid in the resuscitation of hemorrhagic shock. Methods: Sprague Dawley rats were randomly assigned to groups (n=8): Sham; Shock groups: (HS of 40% MAP/60-minutes) and Crystalloid Resuscitation (CR) (shed blood + two volumes CR); DPR (shed blood + intraperitoneal 2.5% peritoneal dialysis fluid (IP); FFP (shed blood + one volumes FFP); FFP+DPR (IP dialysis fluid + one volumes FFP). Rats were euthanized after the three and four-hour post-resuscitation (post-RES) period. Protein levels were assessed using quantitative ELISA. UV spectrometry was used to quantify intestinal paracellular leak. Microelectrodes and Laser Doppler Flowmetry (LDF) were used to examine microcirculatory parameters. Results: Following HS, both FFP and DPR decreased intestinal epithelial and endothelial damage. FFP alone resulted in significantly improved flow and oxygenation compared to CR. FFP alone and in conjunction with DPR resulted in the attenuation of small molecule leak across the intestinal barrier. Conclusion: FFP based resuscitation improves intestinal epithelial and endothelial integrity. The addition of DPR can further stabilize the vascular endothelium and recovery intestinal barrier function. Combination therapy with DPR and FFP to mitigate intestinal barrier breakdown following shock could be a novel method of reducing ischemia-induced intestinal permeability and systemic inflammation after trauma.

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