title: Modulation of mesenteric lymph flow and composition by direct peritoneal resuscitation from hemorrhagic shock.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A paired-control experimental animal study.
  
  
  METHODS
  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).
  
  
  METHODS
  Both DPR and saline were placed intraperitoneally at the time of resuscitation.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery, University of Louisville, Louisville, KY 40292, USA. paul.matheson@louisville.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: Chester J
authors.initials: CJ
authors.lastname: Mays
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Hurt
authors.forename: E Rasheid
authors.initials: ER
authors.lastname: Zakaria
authors.forename: J David
authors.initials: JD
authors.lastname: Richardson
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018960:Hyaluronan Receptors / Q000097:blood; D006820:Hyaluronic Acid / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008196:Lymph / Q000737:chemistry / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D010530:Peritoneal Dialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014883:Water-Electrolyte Imbalance / Q000628:therapy
chemical_list: D018960:Hyaluronan Receptors; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C069261:interferon gamma (1-39); D007371:Interferon-gamma; D006820:Hyaluronic Acid