Hemorrhagic shock and resuscitation (HS/RES) causes ischemia-induced intestinal permeability due to intestinal barrier breakdown, damage to the endothelium, and tight junction (TJ) complex disruption between enterocytes. The effect of hemostatic resuscitation with blood products on this phenomenon is unknown. Previously we showed that Fresh Frozen Plasma (FFP) RES, with or without Directed Peritoneal Resuscitation (DPR) improved blood flow and alleviated organ injury and enterocyte damage following HS/RES. We hypothesized that FFP might decrease tight junction injury and attenuate ischemia-induced intestinal permeability following HS/RES.
Sprague Dawley rats were randomly assigned to groups (n=8): Sham; CR (HS of 40% MAP/60-minutes) and Crystalloid Resuscitation (CR) (shed blood + two volumes CR); CR+DPR (intraperitoneal 2.5% peritoneal dialysis fluid (IP)); FFP (shed blood + one volumes FFP); FFP+DPR (IP dialysis fluid + two volumes FFP). FITC-Dextran-4K was instilled into the GI tract prior to hemorrhage; FITC-Dextran-4K was measured by UV spectrometry at various time points. Plasma syndecan-1 and ileum tissue TJ proteins were measured using ELISAs. Immunofluorescence was used to visualize claudin-4 concentrations at 4-hours following HS/RES.
Following HS, FFP attenuated FITC-Dextran leak across the intestine at all time points compared to CR and DPR alone. This response was significantly improved with the adjunctive DPR at 3-and 4-hours post-resuscitation (p < 0.05). Resuscitation with FFP + DPR increased intestinal tissue concentrations of TJ proteins and decreased plasma syndecan-1. Immunofluorescence demonstrated decreased mobilization of claudin-4 in both FFP and FFP+DPR groups.
FFP based resuscitation improves intestinal tight junction and endothelial integrity. The addition of DPR can further stabilize TJs and attenuate intestinal permeability. 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.
Study Type and Level of Evidence