Modulation of Mesenteric Lymph Flow and Composition by Direct Peritoneal Resuscitation From Hemorrhagic Shock | Bleeding and Transfusion | JAMA Surgery | JAMA Network
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Hassoun  HTKone  BCMercer  DWMoody  FGWeisbrodt  NWMoore  FA Post-injury multiple organ failure: the role of the gut.  Shock 2001;15 (1) 1- 10PubMedGoogle ScholarCrossref
Fruchterman  TMSpain  DAWilson  MAHarris  PDGarrison  RN Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock.  Shock 1998;10 (6) 417- 422PubMedGoogle ScholarCrossref
Wang  PHauptman  JGChaudry  IH Hemorrhage produces depression in microvascular blood flow which persists despite fluid resuscitation.  Circ Shock 1990;32 (4) 307- 318PubMedGoogle Scholar
Zakaria  RSpain  DAHarris  PDGarrison  RN Resuscitation regimens for hemorrhagic shock must contain blood.  Shock 2002;18 (6) 567- 573PubMedGoogle ScholarCrossref
Deitch  EAXu  DFranko  LAyala  AChaudry  IH Evidence favoring the role of the gut as a cytokine-generating organ in rats subjected to hemorrhagic shock.  Shock 1994;1 (2) 141- 145PubMedGoogle ScholarCrossref
Wang  PHauptman  JGChaudry  IH Hepatocellular dysfunction occurs early after hemorrhage and persists despite fluid resuscitation.  J Surg Res 1990;48 (5) 464- 470PubMedGoogle ScholarCrossref
Wang  PBa  ZFChaudry  IH Endothelial cell dysfunction occurs very early following trauma-hemorrhage and persists despite fluid resuscitation.  Am J Physiol 1993;265 (3, pt 2) H973- H979PubMedGoogle Scholar
Zakaria  RGarrison  RNSpain  DAHarris  PD Impairment of endothelium-dependent dilation response after resuscitation from hemorrhagic shock involved postreceptor mechanisms.  Shock 2004;21 (2) 175- 181PubMedGoogle ScholarCrossref
Zweifach  BW Mechanisms of blood flow and fluid exchange in microvessels: hemorrhagic hypotension model.  Anesthesiology 1974;41 (2) 157- 168PubMedGoogle ScholarCrossref
Hierholzer  CHarbrecht  BMenezes  JM  et al.  Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock.  J Exp Med 1998;187 (6) 917- 928PubMedGoogle ScholarCrossref
Schmid-Schönbein  GWHugli  TE A new hypothesis for microvascular inflammation in shock and multi-organ failure: self-digestion by pancreatic enzymes.  Microcirculation 2005;12 (1) 71- 82PubMedGoogle ScholarCrossref
Moore  FAMoore  EEPoggetti  R  et al.  Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma.  J Trauma 1991;31 (5) 629- 636; discussion, 636-638PubMedGoogle ScholarCrossref
Dayal  SDHauser  CJFeketeova  E  et al.  Shock mesenteric lymph-induced rat polymorphonuclear neutrophils activation and endothelial cell injury is mediated by aqueous factors.  J Trauma 2002;52 (6) 1048- 1055; discussion, 1055PubMedGoogle ScholarCrossref
Moran  AAkcan Arikan  AMastrangelo  MA  et al.  Prevention of trauma and hemorrhagic shock-mediated liver apoptosis by activation of Stat 3alpha.  Int J Clin Exp Med 2008;1 (3) 213- 247PubMedGoogle Scholar
Zakaria  RGarrison  RNSpain  DAMatheson  PJHarris  PDRichardson  JD Intraperitoneal resuscitation improves intestinal blood flow following hemorrhagic shock.  Ann Surg 2003;237 (5) 704- 713PubMedGoogle Scholar
Garrison  RNConn  AAHarris  PDZakaria  ER Direct peritoneal resuscitation as adjunct to conventional resuscitation from hemorrhagic shock: a better outcome.  Surgery 2004;136 (4) 900- 908PubMedGoogle ScholarCrossref
Zakaria  ERGarrison  RNKawabe  THarris  PD Direct peritoneal resuscitation (DPR) from hemorrhagic shock: effect of time delay in initiating therapy.  J Trauma 2005;58 (3) 499- 506; discussion, 506-508Google ScholarCrossref
Zakaria  RHurt  RTMatheson  PJGarrison  RN A novel method of peritoneal resuscitation improves organ perfusion after hemorrhagic shock.  Am J Surg 2003;186 (5) 443- 448PubMedGoogle ScholarCrossref
Zakaria  RCampbell  JEPeyton  JCGarrison  RN Postresuscitation tissue neutrophils infiltration is time-dependent and organ-specific.  J Surg Res 2007;143 (1) 119- 125PubMedGoogle ScholarCrossref
Zakaria  RLi  NMatheson  PJGarrison  RN Cellular edema regulates tissue capillary perfusion after hemorrhage resuscitation.  Surgery 2007;142 (4) 487- 496PubMedGoogle ScholarCrossref
Zakaria  RMatheson  PJFlessner  MFGarrison  RN Hemorrhagic shock and resuscitation-mediated tissue water distribution is normalized by adjunctive peritoneal resuscitation.  J Am Coll Surg 2008;206970- 983Google ScholarCrossref
Senthil  MBrown  MXu  DZLu  QFeketeova  EDeitch  EA Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple organ dysfunction syndrome: validating studies in a porcine model.  J Trauma 2006;60 (5) 958- 967PubMedGoogle ScholarCrossref
Drucker  WRChadwick  CDGann  DS Transcapillary refill in hemorrhage and shock.  Arch Surg 1981;116 (10) 1344- 1353PubMedGoogle ScholarCrossref
Deitch  EAXu  DKaiser  VL Role of the gut in the development of injury and shock-induced SIRS and MODS: the gut-lymph hypothesis, a review.  Front Biosci 2006;11520- 528PubMedGoogle ScholarCrossref
Davidson  MTDeitch  EALu  Q  et al.  A study of the biologic activity of trauma-hemorrhagic shock mesenteric lymph over time and the relative role of cytokines.  Surgery 2004;136 (1) 32- 41PubMedGoogle ScholarCrossref
Watkins  ACCaputo  FJBadami  CD  et al.  Mesenteric lymph duct ligation attenuates lung injury and neutrophil activation after intraperitoneal injection of endotoxin in rats.  J Trauma 2008;64 (1) 126- 130PubMedGoogle ScholarCrossref
Badami  CDSenthil  MCaputo  FJ  et al.  Mesenteric lymph duct ligation improves survival in a lethal shock model.  Shock 2008;30 (6) 680- 685Google ScholarCrossref
Berg  SJansson  IHesselvik  FJLaurent  TCLennquist  SWalther  S Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.  Crit Care Med 1992;20 (9) 1315- 1321PubMedGoogle ScholarCrossref
Engström-Laurent  ALoof  LNyberg  ASchroder  T Increased serum levels of hyaluronate in liver disease.  Hepatology 1985;5 (4) 638- 642PubMedGoogle ScholarCrossref
Suehiro  TBoros  PEmre  S  et al.  Assessment of liver allograft function by hyaluronic acid and endothelin levels.  J Surg Res 1997;73 (2) 123- 128PubMedGoogle ScholarCrossref
Berg  SBrodin  BHesselvik  FLaurent  TCMaller  R Elevated levels of plasma hyaluronan in septicemia.  Scand J Clin Lab Invest 1988;48 (8) 727- 732PubMedGoogle ScholarCrossref
Wang  PBa  ZFBiondo  AChaudry  I Liver endothelial cell dysfunction occurs early following hemorrhagic shock and persists despite crystalloid resuscitation.  J Surg Res 1996;63 (1) 241- 247PubMedGoogle ScholarCrossref
McDonald  B McAvoy  EFLam  F  et al.  Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophils sequestration in inflamed liver sinusoids.  J Exp Med 2008;205 (4) 915- 927PubMedGoogle ScholarCrossref
July 20, 2009

Modulation of Mesenteric Lymph Flow and Composition by Direct Peritoneal Resuscitation From Hemorrhagic Shock

Author Affiliations

Author Affiliations: Departments of Surgery (Drs Matheson, Richardson and Garrison, and Mr Mays), Internal Medicine (Dr Hurt), and Physiology and Biophysics (Drs Hurt, Zakaria, and Garrison), University of Louisville, and Louisville Veterans Affairs Medical Center (Drs Hurt and Garrison), Kentucky.

Arch Surg. 2009;144(7):625-634. doi:10.1001/archsurg.2009.125

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.