The Effect of Danaparoid Sodium (Danaparoid) on Endotoxin-induced Experimental Disseminated Intravascular Coagulation (DIC) in Rats

Fujishima, Yuko; Yokota, Koichi; Sukamoto, Takayuki

doi:10.1016/s0049-3848(98)00094-2

Cited by 16 publications

(7 citation statements)

References 18 publications

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“…The traditional anticoagulant heparin, especially at high therapeutic dosages, is effective in interrupting intravascular clotting in cases of acute DIC, which confirms the results of clinical studies in humans as well as experimental studies on rats and rabbits [23,24] . In the present study, a high dose of heparin (500 000 IU/kg) was used for modulation of the DIC process and aided in prevention as well as treatment.…”

Section: Discussionsupporting

confidence: 77%

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

Lin

Sun

2012

Acta Pharmacol Sin

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Aim: To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Methods: LPS-induced DIC model was made in adult male New Zealand rabbits by continuous intravenous infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000 IU/kg) through continuous infusion via the contralateral marginal ear vein for 6 h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken for biochemical analyses. Results: Continuous infusion of LPS into the rabbits gradually impaired the hemostatic parameters, damaged renal and liver functions, increased the plasma TNF-α level, and led to a high mortality rate (80%). Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin-fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels of fibrinogen and platelets; and reversed the decline in activity of protein C and antithrombin III. Meanwhile, the treatment significantly suppressed the increase in the plasma levels of aminotransferase, creatinine and TNF-α, and led to much lower mortality (46.7% and 26.7% for the medium-and high-dose groups). Treatment of the rabbits with the high dose of heparin also effectively improved the hemostatic parameters, ameliorated liver and renal injuries, and reduced the plasma level of TNF-α, and significantly reduced the mortality (33.3%). Conclusion: Tan IIA exerts a protective effect against DIC in rabbits.

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Section: Discussionsupporting

confidence: 77%

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

Lin

Sun

2012

Acta Pharmacol Sin

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“…In experimental fecalperitonitis,heparin ameliorated peritoneal fibrin deposition and favorably affected survivaltime,blood pressure, leukocyte countsa nd lung injury ( 96,97), and improvedthe haematologic abnormalities compatible with DICina sepsis modelinrats (98). In rodent LPS and sepsis models, treatment by heparin (-likecompounds) wasabletodiminish coagulation activation, (renal)fibrin deposits, microthrombi in lung and livera nd to improve hepatocellular function and survival (99)(100)(101)(102)(103). Inhalation of heparina ttenuatesa cutel ung injury (ALI) followings mokei nhalation and bacterial pneumonia in sheep, while intravenous heparinm ay be less helpful in sheep and ratsa lthough attenuating ALIi ne ndotoxaemic pigs (104)(105)(106)(107).In-vitro heparin mayenhancesurfactant protein gene expression in pneumocytes (108).I nar ecent,s ustained and ovine LPS-induced shockmodel (109),unfractionated heparin, hirudin or saline wasgiven.…”

Section: Heparin Treatment In Sepsis Animalmodelsmentioning

confidence: 99%

The role of heparin and allied compounds in the treatment of sepsis

Cornet¹,

Smit²,

Beishuizen³

et al. 2007

Thromb Haemost

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The crosstalk between coagulation and inflammation and the propensity for microthromboembolic disease during sepsis calls for anticoagulant measures to prevent tissue hypoxygenation and to attenuate organ damage and dysfunction. Only one anticoagulant, recombinant human activated protein C (aPC, drotrecogin-alpha) has a proven survival benefit when used as an adjunctive therapy for human sepsis, partly because of its anti-inflammatory effect. However, heparin (-like compounds) may exert similar beneficial anti-inflammatory actions as aPC, in spite of the relatively narrow therapeutic window for anticoagulation. This narrative review is based on a Medline search of relevant basic and clinical studies published in English and discusses the potential role of heparin in modulating inflammatory responses in the treatment of animal models and human sepsis and its harmful sequelae. In any case, the results of a meta-analysis based on animal data suggest a potentially life-saving effect of heparin (-like compounds) in the treatment of sepsis. Therefore, a prospective randomized clinical trial is called upon to study effects in human sepsis.

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“…Danaparoid sodium (DS), aheparinoid thatcontains mainlyheparan sulfate, has been used in the treatment of disseminatedintravascularc oagulation (DIC) in Japan ( 1). Since the anti-Xa /anti-thrombin activity of DS is higher thant hat of unfractionatedheparin (UFH) (2), DS showsalowerfrequencyofbleeding thanU FH in thet reatment of DIC (1). Thep athologic mechanisms leading to DICvarydepending on the natureofunderlying diseases (3).…”

Section: Introductionmentioning

confidence: 99%

Danaparoid sodium reduces ischemia/reperfusion-induced liver injury in rats by attenuating inflammatory responses

Harada¹,

Okajima²,

Kohmura³

et al. 2007

Thromb Haemost

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SummaryThis study was undertaken to examine the mechanism by which danaparoid sodium (DS), a heparinoid that contains mainly heparan sulfate, prevents reperfusion-induced hepatic damage in a rat model of ischemia/reperfusion (I/R)-induced liver injury. Administration of DS significantly reduced liver injury and inhibited the decrease in hepatic tissue blood flow in rats. DS attenuated hepatic I/R-induced increases in hepatic tissue levels of tumor necrosis factor (TNF) and myeloperoxidase (MPO) in vivo. In contrast, neither monocytic TNF production nor neutrophil activation was inhibited by DS in vitro. DS enhanced I/R-induced increases in levels of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory neurons, and of 6-ketoprostaglandin (PG) F1α, a stable metabolite of PGI2, in liver tissues. The therapeutic effects of DS were not seen in animals pretreated with capsazepine, an inhibitor of sensory neuron activation. The distribution of heparan sulfate in the perivascular area was significantly increased by DS administration in this rat model. DS significantly increased CGRP release from isolated rat dorsal root ganglion neurons (DRG) in vitro, while DX-9065a, a selective inhibitor of activated factor X, did not. DS enhanced anandamide-induced CGRP release from DRG in vitro. These observations strongly suggested that DS might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects of DS might be at least partly explained by its enhancement of sensory neuron activation, leading to the increase the endothelial production of PGI2.

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The Effect of Danaparoid Sodium (Danaparoid) on Endotoxin-induced Experimental Disseminated Intravascular Coagulation (DIC) in Rats

Cited by 16 publications

References 18 publications

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

Tanshinone IIA protects rabbits against LPS-induced disseminated intravascular coagulation (DIC)

The role of heparin and allied compounds in the treatment of sepsis

Danaparoid sodium reduces ischemia/reperfusion-induced liver injury in rats by attenuating inflammatory responses

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