Platelet-endothelial cell interactions during hepatic ischemia-reperfusion in vivo: a systematic analysis.
Platelets have been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury. This study was designed to analyze platelet-endothelial cell interactions after I/R of the liver in vivo in dependence of the duration of ischemia and reperfusion. In C57BL/6 mice, a warm (37 degrees C) lobar hepatic ischemia was induced for 30, 60, or 90 min. Platelets were isolated from syngeneic donors, labeled ex vivo by rhodamine-6G, and infused intraarterially. Platelet-endothelial cell interactions and sinusoidal perfusion were analyzed using intravital fluorescence microscopy after 20-240 min of reperfusion. Hepatic I/R induced platelet rolling and adhesion in terminal arterioles and postsinusoidal venules as well as platelet accumulation in sinusoids already after 20 min of reperfusion. The number of platelets interacting with the endothelium was significantly increased as ischemia time was prolonged from 30 min up to 60 and 90 min. Postischemic platelet adhesion was associated with an increase in thrombin activity and a loss of platelets from the systemic circulation. Moreover, I/R-induced platelet adhesion was linearly correlated with an impairment of sinusoidal perfusion. The prolongation of reperfusion time up to 4 h did not further enhance platelet-endothelial cell interactions. These in vivo results indicate that hepatic I/R induces platelet-endothelial cell interactions in arterioles, sinusoids, and venules already during early reperfusion. The extent of these interactions is dependent on the duration of ischemia, but not on reperfusion time. Adherent platelets seem to participate in the development of sinusoidal perfusion failure in the postischemic liver.
Khandoga
Andrej
A
Institute for Surgical Research, University of Munich, 81377, Munich, Germany.
Biberthaler
Peter
P
Messmer
Konrad
K
Krombach
Fritz
F
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D007511:Ischemia; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D013696:Temperature; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
D013917:Thrombin