Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple-organ dysfunction syndrome: validating studies in a porcine model.
BACKGROUND
Trauma-hemorrhagic shock (T/HS) mesenteric lymph from rats has multiple biological properties and appears to cause organ injury via the activation of neutrophils and endothelial cells. As the next step in testing the potential clinical relevance of these rodent studies, we utilized a swine T/HS model to determine whether the intestinal lymph results observed in the rodent could be replicated in swine. A porcine model was chosen because the pig and human cardiovascular and gastrointestinal physiology are similar.


METHODS
Male pigs were subjected to T/HS and a major intestinal lymph duct was cannulated. Hemorrhagic shock (mean arterial pressure, 40 mm Hg) was performed by withdrawing blood, for 3 hours or until the base deficit reached -5. Animals were then resuscitated in two stages to mimic the prehospital and hospital phases of resuscitation. Mesenteric lymph was collected hourly throughout the experiment and its biological activity was tested on neutrophils (respiratory burst) and endothelial cells (monolayer permeability and cytotoxicity).


RESULTS
T/HS lymph but not trauma-sham shock lymph (T/SS) increased neutrophil activation as reflected by an augmented respiratory burst. Likewise T/HS lymph collected at all time points up to 5 hours postshock significantly increased endothelial cell permeability by twofold or greater (p < 0.05), whereas T/HS lymph produced during the first 2 hours postshock was cytotoxic for endothelial cells (viability 70%, p < 0.05 vs. preshock). In contrast, T/SS lymph had no effect on the endothelial cells.


CONCLUSIONS
This large animal model validates rodent studies showing that the shock-injured gut releases biologically active factors into the mesenteric lymph and these factors activate neutrophils and injure endothelial cells.
Senthil
Maheswari
M
Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Brown
Margaret
M
Xu
Da-Zhong
DZ
Lu
Qi
Q
Feketeova
Eleonora
E
Deitch
Edwin A
EA