Antithrombin Prevents Endotoxin-Induced Hypotension in Rats by Inhibiting Induction of Nitric Oxide Synthethase

Okajima, Kiyoko; Murakami, Kazutoshi; Harada, Naoaki

doi:10.1097/00003246-199901001-00070

Cited by 5 publications

(2 citation statements)

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“…Moreover,A Tp revented endotoxin-inducedi njuryi nr at lungsb yi nhibiting neutrophil activation (38). AT furtherr educed endotoxin-induced hypotension (39) and ischemia/reperfusion-associatedrenal injury (40). In contrast, hirudin could not be shown to influenceleukocyterolling and leukocyte adherence to the vasculare ndothelium under light exposure (30).D uring endotoxemia hirudin wasevenfound to stimulate leukocyte adherencea nd to deteriorate endotoxin-inducedc apillary perfusion failure (41).…”

Section: Effectsofheparin Hirudin and At On Microvascular Thromboticmentioning

confidence: 99%

Antithrombin is as effective as heparin and hirudin to prevent formation of microvascular thrombosis in a murine model

Sorg¹,

Hoffmann²,

Menger³

et al. 2006

Thromb Haemost

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A recently published post-hoc analysis of a trial using high-dose antithrombin (AT) in septic patients (KyberSept) revealed significant reduction of lethality when no concomitant heparin was administered, whereas patients with the combination of heparin and AT did not benefit in terms of survival. Therefore, it seems feasible to study the capability of AT in prevention of microvascular thrombus formation to avoid concomitant application of heparin and AT. Using fluorescence microscopy and a light/dye-injury mouse ear model, the kinetics of thrombus formation were analyzed quantitatively in vivo upon single iv bolus of saline (control), heparin (100 IU/kg), hirudin (1 mg/kg) or AT (25, 50, 100 or 250 IU/kg) (N = 7 animals per group each). In controls, light/dye-injury induced complete thrombotic occlusion in all arterioles and venules studied. Heparin and hirudin prevented thrombotic vessel occlusion in 62% and 43% of arterioles and 11% and 28% of venules. AT-250 was found to be more effective than heparin and hirudin, because thrombus formation was completely banned in all arterioles and venules. AT-100 and AT-50 were also capable of significantly blocking thrombus formation in both arterioles and venules. In blood vessels, which finally clogged, the time for development of complete vessel occlusion was delayed after heparin, hirudin and AT-25, but in particular after AT-50 and AT-100. In conclusion, AT-mediated antithrombotic activity has been characterized in a model of phototoxicity-induced microvascular thrombosis formation, demonstrating that AT delays and prevents thrombus formation in arterioles and venules at least comparably effective as heparin and hirudin.

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Section: Effectsofheparin Hirudin and At On Microvascular Thromboticmentioning

confidence: 99%

Antithrombin is as effective as heparin and hirudin to prevent formation of microvascular thrombosis in a murine model

Sorg¹,

Hoffmann²,

Menger³

et al. 2006

Thromb Haemost

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show abstract

“…ATIII blocks FXainduced IL-6, IL-8, MCP-1, ICAM/VCAM, and E-selectin expressions [146] in addition to arresting FIIa-induced (PAR-1-dependent) VEGF release [92] and MCP-1 expression [147]. Apart from inactivating NF B [148], AT III direct antiinflammatory action includes the suppression in INF-and ILs (e.g., 1, 2, 4, 6 & 8) production, which is mediated by enhanced PGI production and diminished inducible nitric oxide synthase (iNOS) [149]. However, the discrepancy exists concerning the survival rate beings improved in baboons [150] but not in severe human sepsis treated with the high dose of ATIII [151].…”

Section: Antithrombin III (Atiii)mentioning

confidence: 99%

Blood Coagulation as an Intrinsic Pathway for Proinflammation: A Mini Review

Chu¹

2010

IADT

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Blood coagulation could be recognized as intrinsic inflammation. The coagulant mediators (FVIIa, FXa, thrombin (FIIa), FXIIa) and fibrin(ogen) activate cellular signaling, eliciting the production of cytokines, chemokines, growth factors, and other proinflammatory mediators. Hypercoagulability with elevated coagulant mediators would certainly trigger hyper-inflammatory state not to mention about the direct hypercoagulable actions on thrombosis, and platelet and complement activations, all of which contribute to inflammatory events. Furthermore, anticoagulant's anti-inflammatory effects readily reinforce the proposal that blood coagulation results in inflammation. The observations on protease activated receptor (PAR) activation and PAR antagonists modulating inflammation are also in line with the concept of coagulation-dependent inflammation.

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Antithrombin III Enhances Inducible Nitric Oxide Synthase Gene Expression in Vascular Smooth Muscle Cells

Totzke

Smolny

Seibel

et al. 2001

Cellular Immunology

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Antithrombin Prevents Endotoxin-Induced Hypotension in Rats by Inhibiting Induction of Nitric Oxide Synthethase

Cited by 5 publications

References 0 publications

Antithrombin is as effective as heparin and hirudin to prevent formation of microvascular thrombosis in a murine model

Antithrombin is as effective as heparin and hirudin to prevent formation of microvascular thrombosis in a murine model

Blood Coagulation as an Intrinsic Pathway for Proinflammation: A Mini Review

Antithrombin III Enhances Inducible Nitric Oxide Synthase Gene Expression in Vascular Smooth Muscle Cells

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