Pentoxifylline attenuates leukocyte-endothelial interactions in a two-hit model of shock and sepsis

Author(s)

Nakagawa, Naomi Kondo ^[1] ; Cruz, Jr., Ruy J. ^[2] ; Aikawa, Priscila ^[3] ; Correia, Cristiano J. ^[1] ; Miranda Costa Cruz, Jose Walber ^[1] ; Mauad, Thais ^[3] ; Zhang, Haibo ^[4] ; Rocha-e-Silva, Mauricio ^[1] ; Sannomiya, Paulina ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Cardiovasc Surg & Circulat Pathophysiol LIM 1, Heart Inst InCor, Sao Paulo - Brazil

^[2] Univ Pittsburgh, Sch Med, Dept Surg, Starzl Transplantat Inst, Pittsburgh, PA - USA

^[3] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[4] Univ Toronto, Dept Anesthesia, Kennan Res Ctr, Li Ka Shing Knowledge Inst, St Michael Hosp, Toronto, ON M5S 1A1 - Canada

• Document type: Journal article
• Source: JOURNAL OF SURGICAL RESEARCH; v. 193, n. 1, p. 421-428, JAN 2015.
• Web of Science Citations: 4

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. Materials and 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 x shed blood volume); HS + PTX (4 mL/Kg + 25 mg/kg PTX); and LR + PTX (3 x shed blood volume = 25 mg/kg PTX). After 48 h of being exposed to the double injury, leukocyte eendothelial 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 mu m venule length (sixfold), migrated leukocytes per 5000 mu m(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 thatpentoxifylline attenuates microcirculatory disturbances at the mesenteric bed with significant minimization of lung inflammation after a double-injury model of hemorrhagicshock and reperfusion followed by sepsis. (C) 2015 Elsevier Inc. All rights reserved. (AU)