Modulation of leukocyte-endothelial interaction by direct peritoneal resuscitation from hemorrhagic shock.

摘要

Background. Conventional resuscitation of hemorrhagic shock that restores and maintains central hemodynamics is associated with a progressive splanchnic vasoconstriction and hypoperfusion, a gut derived systemic inflammatory response (SIRS), and obligatory fluid sequestration. Instillation of a glucose-based clinical peritoneal dialysis solution intraperitoneally as an adjunct to conventional resuscitation from hemorrhagic shock has been shown to improve survival. This adjunctive direct peritoneal resuscitation (DPR) restores adequate end-organ perfusion, down-regulates SIRS and promotes early fluid mobilization. Primed neutrophils and their interaction with activated vascular endothelium is an integral part of the SIRS observed after resuscitation from hemorrhagic shock. Therefore, we hypothesize that DPR-mediated down-regulation of SIRS might occur through mechanisms of endothelial-leukocyte interaction ameliorization.; Methods. Intestinal intravital microscopy (IVM), tissue myeloperoxidase (MPO) assays, and gene expression profiles helped in our ascertainment of the beneficial effects of adjunct DPR when compared to HSCR alone. IVM was used to measure numbers of leukocyte rolling in terminal ileum post capillary venules in 30 second time periods. MPO, a marker of neutrophil sequestration, and also total water content were assessed in the second study in the gut, lung, and liver in sham animals and at time-points 1, 2, 4 and 24 hours post-resuscitation. Gene expression profiles associated with endothelial inflammation were compared via RNA isolation and microarray analysis for tissues of the ileum, lung, and liver at times 2 and 24 hours.; Results. The PD solution significantly attenuated leukocyte-endothelium interaction in sham-operated animals while no significant attenuation was elicited after adjunctive DPR from hemorrhagic shock and resuscitation. Tissue MPO level, an index of neutrophil sequestration, increases in all tissues in a near-linear fashion during the 4 hours following resuscitation from hemorrhagic shock regardless of the resuscitation regimen used. Adjunctive DPR caused significant attenuation in the gene expression of adhesion molecules in tissues of the ileum, lung, and liver early at two hours post-resuscitation. Gene expression changes are time-dependent and organ-specific.; Conclusion. Superfusion of the gut with glucose-based peritoneal dialysis solutions decreases the concentration of rolling leukocytes along the venular vascular endothelium by a vasodilation-mediated increase in blood flow. Hemorrhage and resuscitation-enhanced leukocyte rolling and sequestration was not reversed by adjunctive DPR despite the enhanced blood flow, suggesting a subordinate role of blood rheology in the hemorrhage-induced neutrophil sequestration. However, adjunctive DPR differentially decreases the expression of adhesion molecules genes in a time-dependent and tissue-specific fashion.