Dalteparin sodium treatment during resuscitation inhibits hemorrhagic shock-induced leukocyte rolling and adhesion in the mesenteric microcirculation.

Abstract

Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte (PMN) adhesion and extravasation are pivotal for the development of postinjury multiple organ failure. We hypothesized that the deleterious microcirculatory consequences of hemorrhagic shock (HS) could be altered by low-molecular-weight heparin (LMWH) therapy. Our aim was to investigate the effects of dalteparin sodium on leukocyte-endothelial cell interactions when LMWH treatment was initiated before HS or during resuscitation. Anesthetized dogs underwent HS (40 mm Hg mean arterial pressure for 60 minutes) and resuscitation either with shed blood or with lactated Ringer's (LR) solution. LMWH or conventional heparin sodium pretreatment was administered subcutaneously before hemorrhage; or LMWH was given intravenously during resuscitation. Mesenteric postcapillary venules were observed by intravital video microscopy before and after HS, and 60 minutes, 120 minutes, and 180 minutes after resuscitation, and leukocyte rolling and firm adherence were determined. HS significantly increased PMN rolling and adhesion in the mesenteric microcirculation. LMWH, but not heparin sodium pretreatment, significantly inhibited both primary and secondary interactions. LMWH treatment was also effective when initiated during resuscitation. LMWH exerted the same inhibitory effect regardless of the type of resuscitation. LMWH treatment during resuscitation effectively inhibits PMN rolling and adhesion.