Lipopolysaccharide attenuates thrombolysis in batroxobin-induced lung vasculature fibrin deposition but not in ferrous chloride-induced carotid artery thrombus in rats: role of endogenous PAI-1

Thromb Res. 2003;111(6):381-7. doi: 10.1016/j.thromres.2003.09.026.

Abstract

In this study, we investigated if elevation of endogenous plasminogen activator inhibitor type 1 (PAI-1) by lipopolysaccharide (LPS) can retard thrombolysis in both a rat model of lung vasculature fibrin deposition and a platelet-rich thrombus model induced by endothelial injury. By 3 h following an intravenous bolus injection of 0.5 mg/kg LPS, the plasma PAI-1 level had increased to approximately 8 ng/ml. 125I-labeled fibrinogen was injected intravenously followed by an injection of batroxobin. Batroxobin converts fibrinogen into insoluble fibrin, which was then deposited in the lungs within 5 min, followed by spontaneous fibrinolysis that completely cleared fibrin deposition in the lungs by 30 min. In rats pre-treated with LPS, spontaneous fibrinolysis was significantly retarded. In the endothelial injury model, topical application of FeCl2 on the carotid artery induced an occlusive platelet-rich thrombus, which was not sensitive to endogenous thrombolysis. Exogenous tissue-type plasminogen activator (tPA) was required to recanalize the occlusive thrombus in a dose-dependent manner. Pre-treatment with LPS did not alter the dose-response curve of exogenous tPA-induced thrombolysis. These data indicate that batroxobin-induced lung vasculature fibrin deposition in rats, unlike the FeCl2 model, is sensitive to the impact of endogenous PAI-1 on fibrinolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Batroxobin
  • Carotid Arteries / pathology
  • Carotid Artery Thrombosis / etiology*
  • Ferrous Compounds
  • Fibrin / drug effects
  • Fibrin / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Lung Diseases / etiology*
  • Male
  • Plasminogen Activator Inhibitor 1 / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Plasminogen Activator / metabolism
  • Tissue Plasminogen Activator / pharmacology

Substances

  • Ferrous Compounds
  • Lipopolysaccharides
  • Plasminogen Activator Inhibitor 1
  • Fibrin
  • Batroxobin
  • Tissue Plasminogen Activator
  • ferrous chloride