Hepatic platelet and leukocyte adherence during endotoxemia

Rolands Croner,Tilo Hackert,Christian Herfarth,Martha-Maria Gebhard,Yakup Kulu,Ernst Klar,Elfie Hoerer

doi:10.1186/cc3968

Rolands Croner, Tilo Hackert + Show 5 more

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https://doi.org/10.1186/cc3968

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Abstract

IntroductionLiver microcirculation disturbances are a cause of hepatic failure in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. The time course and reciprocal influences of ongoing microcirculatory events during endotoxemia have not been clarified.MethodsMale Wistar rats (232 ± 17 g) underwent cecal ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3, 5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet rolling in postsinusoidal venules and sticking of leukocytes and platelets in postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR), mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured. Blood count and investigation of hepatic enzyme release was performed after each IVM time point.ResultsHepatic platelet-endothelial adherence in liver sinusoids and postsinusoidal venules occurred one hour after the induction of endotoxemia. Leukocyte-endothelial interaction started three to five hours after CLP. A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was reduced one hour after CLP. HR remained stable and MAP decreased ten hours after CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP.ConclusionHepatic platelet-endothelial interaction is an early event during endotoxemia. Leukocyte adherence occurs later, which underlines the probable involvement of platelets in leukocyte recruitment. Although PBF is reduced immediately after CLP, the later onset of hepatic microperfusion decrease makes the existence of autoregulatory liver mechanisms likely.

Highlights

Liver microcirculation disturbances are a cause of hepatic failure in sepsis
A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after cecal ligation and puncture (CLP), portal venous blood flow (PBF) was reduced one hour after CLP
Hepatic platelet-endothelial interaction is an early event during endotoxemia

Summary

Introduction

Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. Activated endothelial cells produce chemoattractants, such as interleukin-8 and platelet-activating factor, that may be secreted or remain surface bound. Interleukin-8, platelet-activating factor and C5a initiate a cascade of intracellular events that lead to the activation of β-integrins (LFA-1 and Mac-1) [11,12]. These β-integrins enable leukocytes to adhere to endothelial adhesion molecules, such as intercellular adhesion molecules, vascular cell adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1, which initiates extravasation [9,13,14]. The release of superoxide, arachidonic acid metabolites and proteases of transendothelial migrated leukocytes and the impaired microperfusion injures hepatocytes [13,15,16,17,18,19,20]

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