M. A. Wilson2, S. A. Matheson2, P. J. Matheson1,2,3, C. D. Downard1,2, R. N. Garrison1,2,3, J. W. Smith1,2,3 1Robley Rex Veterans Affairs Medical Center,Louisville, KY, USA 2University Of Louisville,Surgery,Louisville, KY, USA 3University Of Louisville,Physiology & Biophysics,Louisville, KY, USA
Introduction: Acute Lung injury (ALI) following hemorrhagic shock (HS) is a life threatening complication. VEGF-A levels correlate with increased pulmonary capillary leak and deranged vascular control mechanisms in ALI. Direct Peritoneal Resuscitation (DPR) increases microvascular perfusion and reduces end organ ischemia in resuscitated hemorrhagic shock (HS/CR). DPR’s effects on pulmonary injury in HS/CR have not been studied. Our goal was to determine DPR effects on the lung injury and VEGF expression following HS/CR.
Methods: Anesthetized Sprague-Dawley rats were randomly assigned to groups (n=8/group): 1) Sham (no HS, no CR, no DPR); 2) HS/CR (HS=40% MAP for 60min, CR=shed blood + volumes NS); 3) HS/CR+DPR at time of CR. All groups were followed for 4hr post RES. Multi-array Luminex was used to measure lung cytokine levels and wet-dry weights were used to evaluate edema formation during resuscitation. PCR SuperArrays were used to assess cellular mRNA levels. Histologic and immunohistochemistry was used to assess pulmonary injury. Pulmonary artery perfusion was evaluated by colorimetric microsphere technique.
Results: DPR enhanced pulmonary blood flow, reduced pulmonary edema, and reduced histologic evidence of pulmonary injury (see Table). Adjunct DPR increased lung perfusion by 111% compared to HS/CR alone (*P<0.01). HS/CR caused lung edema, which was restored to Sham levels in HS/CR+DPR. HS/CR decreased VEGF-A protein levels and adjunct DPR partially restored VEGF-A expression. VEGF-A mRNA levels in HS/CR were down-regulated compared to Sham and adjunct DPR up-regulated VEGF-A mRNA compared to Sham.
Conclusions: Pulmonary edema formation stimulates VEGF-A expression in other forms of ALI, but we observed elevated VEGF expression during reduced pulmonary edema and injury following adjunct DPR treatment. Also, VEGF is thought to preserve endothelial cell function and control, which was consistent with increased pulmonary artery perfusion. ALI-associated edema after resuscitated HS might not play a key role in lung edema in this model. Our data (i.e., VEGF-A protein and mRNA expression) suggest that normalized levels of VEGF are protective of lung perfusion following resuscitated hemorrhagic shock in this model.
