[Involvement of platelet activating factors in pathologic leukocyte-endothelium interactions in the liver after hemorrhagic shock]

Abstract

Introduction: Microcirculatory disturbances and increased adhesion of leukocytes to the hepatic endothelium immediately following hemorrhagic shock have been observed. It is currently discussed, that mediators released by activated macrophages may have regulative functions for these alterations. The aim of the study performed was to investigate the effects of platelet activating factor (PAF) by application of PAF-receptor antagonists in respect to disorders of liver microcirculation and leukocyte adhesion following hemorrhagic shock.

Methods: Sprague-Dawley rats, anesthetized with pentobarbital, were exposed to hemorrhagic shock by depression of the mean arterial blood pressure (MABP) to 40 mmHg for 60 min by controlled blood removal. Three hours following adequate volume replacement together with blood retransfusion (60%) and at normalized MABP as well as supranormal cardiac output levels, the livers of the animals were investigated by intravital microscopy in respect to leukocyte adhesion and microcirculation. Evaluation of the microcirculation of 5 liver lobules/animal was performed on SVHS recorded images using a computer-assisted image analysis system. Three shock groups (n = 6 rats) and one sham-operated control group (n = 8) were compared. Shock/NaCl group received 0.1 ml NaCl 0.9% 15 min prior to shock induction and 1 min prior to shock therapy i. v., respectively. Shock/BN group received a total of 10 mg/kg of the PAF-antagonist BN 52021 (Dr. Braquet, Paris) and Shock/WEB group 2 mg/kg of the PAF antagonist WEB 2086 (Boehringer, Ingelheim), respectively in 2 injections with identical volume.

Results: The course of hemodynamic parameters MABP and cardiac output were comparable in all 3 shock groups. Metabolic parameters such as acid-base state and hematocrit values did not reveal differences. Evaluation of liver microcirculation indicated in all shock groups a reduction of sinusoidal diameters and a slight increase of velocity of leukocytes. The significantly increased temporary adhesion of leukocytes with an adhesion time shorter than 20s in the shock/NaCl group (adhesion index 154.1 +/- 63.2s/100 leukocytes; mean +/- SD) was reduced significantly by the PAF antagonists BN 52021 (82.2 +/- 24.2) and WEB 2086 (86.0 +/- 30.0). Permanent adhesion with an adhesion time longer than 20s was increased significantly particularly in zone I of the liver acinus (portal region) in all shock groups without specific effects of the PAF antagonists.

Conclusions: Liver microcirculation following adequately treated hemorrhagic shock was disturbed, as indicated by narrowed sinusoids and increased adhesion of leukocytes. PAF seems to have no effect on sinusoidal narrowing in this period, however, it seems involved in temporary adhesion of leukocytes. The relevance of these early changes following hemorrhagic shock in respect to the development of organ dysfunction should be further addressed.