Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation-induced pulmonary inflammation through attenuation of neutrophil degranulation and proinflammatory mediator synthesis

被引:31
作者
Deree, Jessica [1 ]
Martins, Joilson O. [1 ]
Leedom, Alex [1 ]
Lamon, Brian [1 ]
Putnam, James [1 ]
de Campos, Tercio [1 ]
Hoyt, David B. [1 ]
Wolf, Paul [1 ]
Coimbra, Raul [1 ]
机构
[1] Univ Calif San Diego, Sch Med, Dept Surg, Div Trauma & Surg Crit Care, San Diego, CA 92103 USA
来源
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE | 2007年 / 62卷 / 01期
关键词
pentoxifylline; hypertonic saline; hemorrhagic shock; acute lung injury; matrix metalloproteinases; heme oxygenase-1; interleukin-8; inflammation;
D O I
10.1097/TA.0b013e31802d96cb
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Ringer's lactate (RL), the current standard resuscitation fluid, potentiates neutrophil activation and is associated with pulmonary inflammation. Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to attenuate hemorrhagic. shock-induced injury when compared with RL. Because the neutrophil plays a major role in post-shock inflammation, we hypothesized that HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL. Methods: Sprague-Dawley rats underwent controlled shock and were resuscitated with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg). Animals who did not undergo shock or resus-citation served as controls. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme-linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and immunohistochemistry. Results: HSPTX resuscitation led to a 62% decrease in CINC levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11% with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p < 0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway epithelial cells. Conclusion: Collectively, the attenuation of pulmonary inflammation with HSPTX after shock when compared with RL is associated with downregulation of neutrophil activation, oxidative stress, and proinflammatory mediator production.
引用
收藏
页码:104 / 111
页数:8
相关论文
共 48 条
[1]   E- and P-selectin expression depends on the resuscitation fluid used in hemorrhaged rats [J].
Alam, HB ;
Sun, L ;
Ruff, P ;
Austin, B ;
Burris, D ;
Rhee, P .
JOURNAL OF SURGICAL RESEARCH, 2000, 94 (02) :145-152
[2]   Role of the neutrophil in septic shock and the adult respiratory distress syndrome [J].
Aldridge, AJ .
EUROPEAN JOURNAL OF SURGERY, 2002, 168 (04) :204-214
[3]   Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock [J].
Angle, N ;
Hoyt, DB ;
Coimbra, R ;
Liu, F ;
Herdon-Remelius, C ;
Loomis, W ;
Junger, WG .
SHOCK, 1998, 9 (03) :164-170
[4]  
BARROSOARANDA J, 1990, BIORHEOLOGY, V27, P401
[5]   Heme oxygenase-1: Redox regulation and role in the hepatic response to oxidative stress [J].
Bauer, M ;
Bauer, I .
ANTIOXIDANTS & REDOX SIGNALING, 2002, 4 (05) :749-758
[6]   Sequential systemic platelet-activating factor and interleukin 8 primes neutrophils in patients with trauma at risk of multiple organ failure [J].
Botha, AJ ;
Moore, FA ;
Moore, EE ;
Peterson, VM ;
Silliman, CC ;
Goode, AW .
BRITISH JOURNAL OF SURGERY, 1996, 83 (10) :1407-1412
[7]   Pulmonary expression of inducible heme-oxygenase after ischemia/reperfusion of the lower extremities in rats [J].
Boutros, CN ;
Zegdi, R ;
Lila, N ;
Combillau, M ;
Fornes, P ;
Carpentier, A ;
Fabiani, JN .
JOURNAL OF SURGICAL RESEARCH, 2005, 129 (02) :306-312
[8]   Metalloproteinase inhibition prevents acute respiratory distress syndrome [J].
Carney, DE ;
McCann, UG ;
Schiller, HJ ;
Gatto, LA ;
Steinberg, J ;
Picone, AL ;
Nieman, GF .
JOURNAL OF SURGICAL RESEARCH, 2001, 99 (02) :245-252
[9]   Regulation of matrix metalloproteinase-9 release from IL-8-stimulated human neutrophils [J].
Chakrabarti, S ;
Patel, KD .
JOURNAL OF LEUKOCYTE BIOLOGY, 2005, 78 (01) :279-288
[10]   Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury [J].
Coe, DA ;
Freischlag, JA ;
Johnson, D ;
Mudaliar, JH ;
Kosciesza, SA ;
Traul, DK ;
Chiang, PC ;
Cambria, RA ;
Seabrook, GR ;
Towne, JB .
JOURNAL OF SURGICAL RESEARCH, 1997, 67 (01) :21-25