title: Pentoxifylline attenuates leukocyte-endothelial interactions in a two-hit model of shock and sepsis.
abstract: BACKGROUND
  This study investigated the effects of pentoxifylline (PTX) combined with resuscitation fluids on microcirculatory dysfunctions in a two-hit model of shock and sepsis.
  
  
  METHODS
  Male Wistar rats (250 g) were submitted to hemorrhagic shock and reperfusion followed by sepsis induced by cecal ligation and puncture. For the initial treatment of shock, rats were randomly divided into: sham, no injury, no treatment; hypertonic saline solution (HS) (7.5%, 4 mL/kg); lactated Ringer's solution (LR, 3 × shed blood volume); HS + PTX (4 mL/Kg + 25 mg/kg PTX); and LR + PTX (3 × shed blood volume + 25 mg/kg PTX). After 48 h of being exposed to the double injury, leukocyte-endothelial interactions were assessed by intravital microscopy of the mesentery. Endothelial expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was evaluated by immunohistochemistry, as well as lung neutrophil infiltration by histology.
  
  
  RESULTS
  Lactated Ringer's solution induced marked increases (P < 0.001) in the number of rolling leukocytes per 10 min (two-fold), adherent leukocytes per 100 μm venule length (six-fold), migrated leukocytes per 5000 μm(2) (eight-fold), P-selectin and ICAM-1 expression (four-fold), and lung neutrophil infiltration (three-fold) compared with sham. In contrast, PTX attenuated leukocyte-endothelial interactions, P-selectin and ICAM-1 expression at the mesentery when associated with either LR (P < 0.001) or HS (P < 0.05). Neutrophil migration into the lungs was similarly reduced by PTX (P < 0.05).
  
  
  CONCLUSIONS
  Data presented showed that pentoxifylline attenuates microcirculatory disturbances at the mesenteric bed with significant minimization of lung inflammation after a double-injury model of hemorrhagic shock and reperfusion followed by sepsis.
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM 11), Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil; Department of Pathology, LIM 5, University of São Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Naomi Kondo
authors.initials: NK
authors.lastname: Nakagawa
authors.affiliation: Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburg, Pennsylvania.
authors.forename: Ruy J
authors.initials: RJ
authors.lastname: Cruz
authors.affiliation: Department of Pathology, LIM 5, University of São Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Aikawa
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM 11), Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Cristiano J
authors.initials: CJ
authors.lastname: Correia
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM 11), Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: José Walber Miranda Costa
authors.initials: JW
authors.lastname: Cruz
authors.affiliation: Department of Pathology, LIM 5, University of São Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.affiliation: Kennan Research Centre of Li Ka Shing Knowledge Institute at Saint-Michael Hospital, Department of Anesthesia, University of Toronto, Ontario, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM 11), Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rocha-e-Silva
authors.affiliation: Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM 11), Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil. Electronic address: exppaulina@incor.usp.br.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
mesh_terms: D000818:Animals; D002432:Cecum / Q000293:injuries; D002450:Cell Communication / Q000187:drug effects*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology; D036904:Leukocyte Rolling / Q000187:drug effects*; D008026:Ligation; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000276:immunology; D014951:Wounds, Stab
chemical_list: D016166:Free Radical Scavengers; D007552:Isotonic Solutions; D019007:P-Selectin; D000077325:Ringer's Lactate; D018799:Intercellular Adhesion Molecule-1; D010431:Pentoxifylline
keywords: Cecal ligation and puncture; Double-injury; Hemorrhagic shock; Intravital microscopy; Microcirculation; Multiple organ failure