Effect of WEB 2086 on leukocyte adherence in response to hemorrhagic shock in rats

被引:7
作者
Childs, EW [1 ]
Smalley, DM [1 ]
Moncure, M [1 ]
Miller, JL [1 ]
Cheung, LY [1 ]
机构
[1] Univ Kansas, Med Ctr, Dept Surg, Kansas City, KS 66160 USA
来源
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE | 2000年 / 49卷 / 06期
关键词
microvascular injury; platelet-activating factor antagonist; mesenteric venules; intravital microscopy;
D O I
10.1097/00005373-200012000-00021
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: The pathogenesis of generalized microvascular injury after hemorrhagic shock is known to involve the generation of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]). The release of PAF is manifested in several ways, including by increased vascular permeability, altered vascular reactivity, and increased leukocyte adherence to the endothelium, WEB 2086 is a PAF antagonist that has been shown experimentally to improve survival after hemorrhagic shock. The purpose of this study was to examine the efficacy of WEB 2086 in attenuating leukocyte adherence before, during, and after hemorrhagic shock. Methods: After a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 minutes in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small bowel were examined to quantitate leukocyte adherence using intravital microscopy, Results: In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in a significant increase in leukocyte adherence post-shock during resuscitation (10.9 +/- 1.8 cells/100 mum, p < 0.01) when compared with controls. WEB 2086, when given before shock, significantly attenuated leukocyte adherence (0.1 +/- 0.08 cells/100 <mu>m, p < 0.01) when compared with hemorrhagic shock alone. This effect of WEB 2086 on adherence could be demonstrated even when it was given during (3.5 +/- 0.9 cells/100 <mu>m, p < 0.01) and 10 minutes into (5.8 +/- 1.1 cells/100 <mu>m, p < 0.05) hemorrhagic shock. Conclusion: Our findings suggest that WEB 2086 may be of therapeutic benefit against the microvascular damage sustained after hemorrhagic shock.
引用
收藏
页码:1102 / 1107
页数:6
相关论文
共 26 条
[1]   Role of platelet-activating factor antagonism in posthemorrhage septic shock in pigs [J].
AbuZidan, FM ;
Walther, S ;
Lennquist, S .
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 1996, 41 (04) :634-640
[2]   ROLE OF PLATELET-ACTIVATING-FACTOR ANTAGONISM IN HEMORRHAGIC-SHOCK IN PIGS [J].
ABUZIDAN, FM ;
WALTHER, S ;
LENNQUIST, S .
EUROPEAN SURGICAL RESEARCH, 1995, 27 (06) :379-388
[3]  
Benveniste J., 1983, ETHER LIPIDS BIOCH B, P355
[4]   PAF and CD18 mediate neutrophil infiltration in upper gastrointestinal tract during intra-abdominal sepsis [J].
Beyer, AJ ;
Smalley, DM ;
Shyr, YM ;
Wood, JG ;
Cheung, LY .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1998, 275 (03) :G467-G472
[5]   PLATELET-ACTIVATING-FACTOR INCREASES LUNG VASCULAR-PERMEABILITY TO PROTEIN [J].
BURHOP, KE ;
GARCIA, JGN ;
SELIG, WM ;
LO, SK ;
VANDERZEE, H ;
KAPLAN, JE ;
MALIK, AB .
JOURNAL OF APPLIED PHYSIOLOGY, 1986, 61 (06) :2210-2217
[6]   Leukocyte adherence and sequestration following hemorrhagic shock and total ischemia in rats [J].
Childs, EW ;
Wood, JG ;
Smalley, DM ;
Hunter, FA ;
Cheung, LY .
SHOCK, 1999, 11 (04) :248-252
[7]   ROLE OF PLATELET-ACTIVATING-FACTOR IN THE DEVELOPMENT OF ENDOTHELIAL DYSFUNCTION IN HEMORRHAGIC HYPOTENSION AND RETRANSFUSION [J].
CSAKI, C ;
SZABO, C ;
BENYO, Z ;
KOVACH, AGB .
THROMBOSIS RESEARCH, 1992, 66 (01) :23-31
[8]  
Debek W, 1998, EXP TOXICOL PATHOL, V50, P19
[9]   Platelet-activating factor modulates leukocyte adhesion to endothelium in ischemia-reperfusion [J].
Duran, WN ;
Milazzo, VJ ;
Sabido, F ;
Hobson, RW .
MICROVASCULAR RESEARCH, 1996, 51 (01) :108-115
[10]  
DURAN WN, 1990, J LIPID MEDIATOR, V2, pS215