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] microL/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] microL/min and 15.6 [1.5] ng/mL), and DPR returned levels to baseline (mean [SEM], 4.4 [0.5] microL/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 gamma, interleukin 1beta, 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.

Enteral glutamine supplementation impairs intestinal blood flow in rats.

BACKGROUND: Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow. METHODS: Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine. RESULTS: There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow. CONCLUSIONS: Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow-transplant patients).