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Abstract

Introduction: Adjunctive direct peritoneal resuscitation (DPR) with hypertonic peritoneal dialysis solution in addition to conventional resuscitation from hemorrhagic shock (HS) mitigates visceral organ injury via improved visceral blood flow (VBF) but the effect on remote organs has not been evaluated. Hypothesis: We hypothesized that DPR would decrease acute lung injury (ALI) after hemorrhagic shock. Methods: Anesthetized rats were bled to 40% MAP for 60 min to induce HS and were randomly assigned to resuscitation with shed blood + NS (CR, n=8), or CR + 30 ml of IP 2.5% Delflex (DPR, n=8). Protein expression was measured using multiplex array and individual ELISA, mRNA expression via PcR and organ injury graded in blinded manner. One way ANOVA with Tukey-Kramer was performed at a significance at p<0.01. Results: Enhanced VBF was seen in the DPR group (not shown). Lung sections from DPR animals had less edema and enhanced structural integrity. Wet to dry weight ratios for the DPR group were decreased compared to CR. (Sham 4.92 ± 0.08; CR 5.37+0.12; DPR 4.91 ± 0.07, p<0.01) Cytosolic migration of HMGB-1 (a nuclear regulatory protein) confirmed the breakdown of nuclear/cellular integrity in CR animals. Nuclear sequestration of HMGB-1 was preserved in the DPR and sham. Serum HMGB-1 levels were increased in CR compared to DPR indicating cellular necrosis with cytosolic release. (1.2 ± 0.2 vs. 6.88 ± 0.9 ng/ml, DPR vs. CR, p<0.01) Th1 serum cytokine levels were reduced in DPR animals when compared to CR. (IL1a: 10.7 ± 0.7 vs. 26.7 ± 2.7 mg/ml; INFg: 1148+23 vs. 1213 ± 88 ng/ml, DPR vs. CR; p<0.01) CR increased lung IL18 and IL12p70 protein (IL18: 5255 ± 535 vs. 6948 ± 545 ng/g; IL12p70: 19.6 ± 0.5 vs. 21.3 ± 0.7 ng/g; DPR vs. CR p<0.01) and increased mRNA expression of IL18 (+1.2 DPR/sham vs. +3.8 CR/sham, P<0.01) indicating activation and expression of these proteins in lung tissue. This correlated with increase serum level in CR compared to DPR. (IL18: 117 ± 17 vs. 213 ± 15 ng/ml; IL-12p70: 14.4 ± 0.9 vs. 13.1 ± 0.5; DPR vs. CR, p<0.01) Conclusions: DPR reduces pulmonary edema and maintains lung cellular and nuclear architecture after HS. DPR decreases shock-induced ALI possibly due to attenuating the Th1 inflammatory response.