Modulation of mesenteric lymph flow and composition by direct peritoneal resuscitation from hemorrhagic shock

Hypothesis: Traditional clinical resuscitation from hemorrhagic shock that focuses on restoring central hemodynamic function does not adequately perfuse the gut. Intestinal hypoperfusion could stimulate ongoing organ failure and gut-derived systemic inflammatory response syndrome. Direct peritoneal resuscitation (DPR) that uses dialysis fluid improves perfusion and survival. We examined mesenteric lymph flow and proinflammatory constituents to determine whether DPR-stabilized interstitial compartment function could explain improved outcomes. Design: A paired-control experimental animal study. Participants: Mesenteric lymph fluid was continuously collected in 4 groups of rats (n=7 per group): sham group; hemorrhagic shock (50% mean arterial pressure for 30 minutes) and resuscitation (shed blood plus 2 volumes of isotonic sodium chloride for 30 minutes) group; hemorrhagic shock and resuscitation plus intraperitoneal saline (30 mL) group; and hemorrhagic shock and resuscitation plus DPR (30 mL of 2.5% clinical peritoneal dialysis fluid). Interventions: Both DPR and saline were placed intraperitoneally at the time of resuscitation. Main Outcome Measures: Lymph composition was analyzed by enzyme-linked immunosorbent assay (ELISA) for hyaluronic acid, its ligand CD44, and cytokines. Results: Hemorrhagic shock and resuscitation elevated lymph flow (peak mean [SEM], 20.6[5.6] μL/min at 60 minutes after resuscitation) and CD44 serum levels (peak mean [SEM], 140.0[12.9] ng/mL at 120 minutes after resuscitation) compared with the sham group (mean [SEM], 1.2[0.7] μL/min and 15.6[1.5] ng/mL), and DPR returned levels to baseline (mean [SEM], 4.4[0.5] μL/min and 15.4[0.3] ng/mL). Hyaluronic acid levels were elevated in the hemorrhagic shock and resuscitation group (mean [SEM], 90.0[1.3] ng/mL) and the hemorrhagic shock and resuscitation plus intraperitoneal saline group (mean [SEM], 93.0[1.3] ng/mL) compared with the sham group (mean [SEM], 73.7[1.4] ng/mL) or DPR group (81.2[0.9] ng/mL). Interferon γ, interleukin 1β, interleukin 6, and interleukin 10 levels were also modulated by DPR. Conclusions: Hemorrhagic shock and resuscitation increased lymph flow by altering capillary water transport and expanding interstitial volume. Increased lymph hyaluronic acid and inflammatory cytokines with traditional resuscitation were modulated to sham levels by DPR. In addition, DPR reduces these patterns presumably via an osmotic effect on capillary water transport. Adjunctive DPR might offer novel protection from systemic inflammatory response syndrome after hemorrhagic shock and resuscitation.