Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats.
BACKGROUND
Prophylactic use of anticoagulants for septic patients in intensive care unit is a standard therapy for the prevention of venous thrombosis. Moreover, recent studies have demonstrated the anti-inflammatory effects of anticoagulants such as Factor Xa inhibitors and heparins. However, there have been no studies to examine the effects of fondaparinux and enoxaparin when applied in a sepsis model. Therefore, we examined the anti-inflammatory effects and bleeding events when these agents are applied in a lipopolysaccharide challenge model.


METHODS
Wistar rats received lipopolysaccharides followed by a bolus infusion of fondaparinux, enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation for endothelial damage and measurement of bleeding area after vascular puncture was performed (n = 6 in each group). In another series, blood samples were taken, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each).


RESULTS
Both leukocyte adherence to vascular endothelium and endothelial damage were reduced in fondaparinux and enoxaparin groups. The bleeding area was markedly increased in the fondaparinux group. Coagulation markers were maintained better in the enoxaparin group. Levels of organ damage markers were significantly suppressed in both fondaparinux and enoxaparin groups (p < 0.01, compared with control, each).


CONCLUSIONS
Fondaparinux and enoxaparin reduce organ dysfunction by decreasing endothelial damage. However, bleeding was more prominent in the fondaparinux group compared with the enoxaparin group at an equipotent dose for anti-Xa activity. Because the setting of this experiment is different from the clinical use, further study is required for the comparison of both pharmaceuticals.
Department of Emergency and Disaster Medicine Juntendo University, Bunkyo-ku, Tokyo, Japan. toshiiba@cf6.so-net.ne.jp
Toshiaki
T
Iba
Kohei
K
Okamoto
Tsubasa
T
Ohike
Toshihiro
T
Tajirika
Koichiro
K
Aihara
Shin
S
Watanabe
Hamzeh
H
Kayhanian
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects*; D019446:Endotoxemia / Q000188:drug therapy*; D017984:Enoxaparin / Q000494:pharmacology / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006470:Hemorrhage / Q000517:prevention & control; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D008070:Lipopolysaccharides; D011134:Polysaccharides; D000077425:Fondaparinux