Pretreatment of Rabbits With Either Hirudin, Ancrod, or Warfarin Significantly Reduces the Immediate Uptake of Fibrinogen and Platelets by the Deendothelialized Aorta Wall After Balloon-Catheter Injury In Vivo

Hatton, M. W. C.; Ross, Bonnie; Southward, Suzanne M.R.; DeReske, Marnie; Richardson, Mary

doi:10.1161/01.atv.18.5.816

Cited by 15 publications

(12 citation statements)

References 37 publications

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“…38 The dose of ancrod was based on our experience with rabbits and a previous study with mice. 37,39 Mice received ancrod (Sigma Chemical) in 4 bolus injections (1 unit in 0.2 mL of saline each) via the retro-orbital sinus, starting 16 hours before LPS challenge (−16 hours, −8 hours, 0 hours, and +8 hours).…”

Section: Ancrod Treatmentmentioning

confidence: 99%

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia

Pawliński

Pedersen

Schabbauer

et al. 2004

Blood

281

279

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Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the downstream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

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Section: Ancrod Treatmentmentioning

confidence: 99%

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia

Pawliński

Pedersen

Schabbauer

et al. 2004

Blood

281

279

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“…To determine the contribution of fibrin deposition to myocardial I/R injury, rabbits (n ϭ 5) were treated with ancrod, a defibrinogenating agent. 26 Ancrod cleaves only the A-chains of fibrinogen producing soluble, uncrosslinked fibrin-fibrinogen degradation products that are cleared by the reticuloendothelial system. Ancrod (Sigma Chemical Co., St. Louis, MO) was administered as previously reported.…”

Section: In Situ Coronary Ligation Modelmentioning

confidence: 99%

“…Ancrod (Sigma Chemical Co., St. Louis, MO) was administered as previously reported. 26 Rabbits received ancrod intravenously beginning with a bolus dose of 1.0 IU/kg, followed by a second bolus dose (1.0 IU/kg) 1 hour later, and a third bolus dose (2.0 IU/kg) 3 hours later. The I/R protocol was initiated 6 hours after the first ancrod dose.…”

Section: In Situ Coronary Ligation Modelmentioning

confidence: 99%

Inhibition of the Tissue Factor-Thrombin Pathway Limits Infarct Size after Myocardial Ischemia-Reperfusion Injury by Reducing Inflammation

Erlich

Boyle

Labriola

et al. 2000

The American Journal of Pathology

190

170

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Functional inhibition of tissue factor (TF) has beenshown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P ‫؍‬ 0.004) and 44% (P ‫؍‬ 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P ‫؍‬ 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R. (Am J Pathol 2000, 157:1849 -1862)

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“…On the other hand, we determined the N-terminal sequence of rabbit fibrinogen in this study. In the rabbit sequence of the N-terminal region corresponding to FPA (A· 1-16) or fibrinopeptide B (FPB; Bß 1-13), only a few amino acid residues (e.g., Phe 8 and Arg 16 in FPA, Arg 13 in FPB) were homologous between rabbit and human or bovine sequences. The variability of FPA and FPB sequences among mammalian species had been reported by Blombäck et al [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Hatton et al [8] demonstrated that thrombin converted fibrinogen to fibrin, and that fibrin-bound thrombin was deposited on the exposed subendothelium after balloon-catheter injury. Speidel et al.…”

Section: Introductionmentioning

confidence: 99%

Bound Thrombin from Crushed Clots Is Composed of α-Thrombin and the N-Terminal Regions of α- and γ-Chains of Fibrinogen

Kinjoh

Nakamura²,

Zeng³

et al. 2002

Pathophysiol Haemos Thromb

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We aimed at clarifying the structural characteristics of the bound thrombin that is liberated by mechanical breakdown of fibrin clots. Fibrin clots were prepared with bovine thrombin and rabbit fibrinogen, and were crushed mechanically with a glass rod. The supernatant of the crushed clots was subjected to immunoaffinity chromatography to isolate the bound thrombin. Western blotting analysis revealed that the bound thrombin could be reacted with both antithrombin and antifibrinogen under unreduced conditions. SDS-PAGE under reduced conditions revealed that there were three bands, two of which were found to be the N-terminal fragments of the α- and γ-chains of fibrinogen. The bound thrombin could be dissociated into three distinct fibrin fragments and bovine α-thrombin when denatured by 8 M urea. Thus, the bound thrombin liberated from crushed clots is a stable complex between bovine α-thrombin and fibrin fragments of the N-terminal regions of rabbit α- and γ-chains.

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Pretreatment of Rabbits With Either Hirudin, Ancrod, or Warfarin Significantly Reduces the Immediate Uptake of Fibrinogen and Platelets by the Deendothelialized Aorta Wall After Balloon-Catheter Injury In Vivo

Cited by 15 publications

References 37 publications

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia

Inhibition of the Tissue Factor-Thrombin Pathway Limits Infarct Size after Myocardial Ischemia-Reperfusion Injury by Reducing Inflammation

Bound Thrombin from Crushed Clots Is Composed of α-Thrombin and the N-Terminal Regions of α- and γ-Chains of Fibrinogen

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