Fibrinolytic action of a new semi-synthetic polysaccharide sulfate, galactan polysulfate (DH 6322), in the rat

Kumada, Toshihiko; Abiko, Yasushi

doi:10.1016/0049-3848(85)90117-3

Cited by 11 publications

(3 citation statements)

References 27 publications

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“…More likely, sulphated polysaccharides modify the complex interactions that occur between components of the fibrinolytic system. Numerous mechanisms have been reported by which heparin-like com pounds enhance fibrinolytic activity in vitro, and it is possible that these operate in vivo: inhibition of antiplasmins (1), activation of the factor Xll-kinin system (18), non-enzymic enhancement of lysis of non cross-linked fibrin clots (2), activation of plasminogen activators (3,4,20), enhancement of the interaction between plasminogen and fibrin (5,6), enhancement of the u-PA catalyzed plasminogenolysis (7,8) and stimulation of the plasmin mediated conversion of single-chain u-PA to two-chain u-PA (9). A change Table 2.…”

Section: Discυssionmentioning

confidence: 99%

“…There is general agreement that their main mechanism of action is through inhibition of the coagulation cascade although enhancement of fibrinolytic activity may be an additional pathway. The latter, however, is uncertain, mainly because the effects of heparin on endogenous fibrinolysis are still not well established, Whilst some in vitrp, animal and human experiments have demonstrated an enhancement of fibrinolytic activity by sulfated polysaccharides (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), there are also a number of studies which show the opposite (absence of effect or even inhibitory effects on fibrinolysis) (19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

Boer

Kluft²,

Dooijewaard³

et al. 1992

Thromb Haemost

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SummaryThe effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran®) (3,250 anti-Xa units i. v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 µg over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen, and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p <0.05). The last difference was considered spurious. scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p >0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system.

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Section: Discυssionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

Boer

Kluft²,

Dooijewaard³

et al. 1992

Thromb Haemost

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“…The mechanism of this potentiation needs to be elucidated. A direct action on t-PA or scu-PA, an increased binding of plasminogen to fibrin, 16 and an increased activation of free plasminogen by t-PA and scu-PA 17,18 could take part in this phenomenon.…”

Section: Effect Of Cy 222 On the Thrombolysis Induced By Tissue-type mentioning

confidence: 99%

Potentiation by Heparin Fragment CY 222 (CHOAY) of Thrombolysis Induced by Human Tissue-Type Plasminogen Activator

Juhan-Vague¹,

Stassen²,

Alessi³

et al. 1989

Semin Thromb Hemost

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Heparin is the standard treatment of deep vein thrombosis; the aim of this treatment is to prevent further thrombus growth, although minimal thrombolysis may be expected. In an animal thrombosis model, 1 ' 2 a significant reduction of the size of the thrombus has been obtained with low molecular weight heparins (LMWH), suggesting that these products may be of value in the curative treatment of thrombosis. A recent comparative study of standard heparin and LMWH showed a similar thrombolytic effect of both drugs but with the latter having no side effect. 3 In order to explain the reduction of the size of the thrombus obtained with heparin or LMWH, several studies attempted to demonstrate a profibrinolytic effect of these drugs. Investigations mainly concerned an effect on the release of tissue-type plasminogen activator (t-PA) by endothelial cells. The results of these studies are controversial.After a single injection of heparin or LMWH in human volunteers, an increase in euglobulin fibrinolytic activity (EFA) was observed 2 and 4 hours after the injection of LMWH, 1,4 and in one study the level of t-PA antigen was shown to be elevated after the injection. 5 However, the increase in EFA could have resulted from circadian fluctuations of the fibrinolytic activity with decrease of the PA inhibitor level in the early afternoon hours. 6 ' 7The observation of an increase in EFA in the eluate of organs perfused with heparin or LMWH 1,8 suggested an effect on the release of t-PA by the vascular bed.The same conclusion was suggested by Arnesen et al, 9 who showed that patients receiving heparin during the pre-and postoperative periods exhibited a larger increase in t-PA activity and t-PA antigen after venous occlusion the third day after surgery than patients not receiving heparin.In patients with deep vein thrombosis receiving high dose of the LMWH CY 222 (Choay, Paris, France), we looked for a relationship between the thrombolytic effect of CY 222 and the change in plasma fibrinolytic parameters: 10 a good thrombolytic effect evaluated by phlebography was obtained after 7 days of treatment but no change in EFA, t-PA antigen, and PA inhibitor occurred during treatment. These results were not consistent with the stimulating effect of CY 222 on the release of t-PA by endothelial cells, or with an effect on PA inhibitor. However, a direct effect of LMWH on the patient's own fibrinolytic system could be involved. To test this hypothesis, we looked for a direct effect of the LMWH CY 222 on t-PA activity and single chain urokinase PA (scu-PA) activity in animal studies: 11 in a model of jugular vein thrombosis in which rabbits received t-PA or scu-PA and standard heparin or LMWH, we found that CY 222 potentiated the thrombolytic effect of t-PA and to a lesser extent of scu-PA. THROMBOLYSIS AND PLASMA FIBRINOLYTIC PARAMETERS IN PATIENTS TREATED WITH CY 222Thirty patients with recently diagnosed (less than 7 days) deep vein thrombosis who had given their informed consent were randomized into three treatment groups and received 4...

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Patents and literature

Linhardt

Wedlock²,

Phillips³

et al. 1987

Appl Biochem Biotechnol

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Fibrinolytic action of a new semi-synthetic polysaccharide sulfate, galactan polysulfate (DH 6322), in the rat

Cited by 11 publications

References 27 publications

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

Influence of Heparin and a Low Molecular Weight Heparinoid on Specific Endogenous and Exogenous Fibrinolytic Factors during Rest and Exercise

Potentiation by Heparin Fragment CY 222 (CHOAY) of Thrombolysis Induced by Human Tissue-Type Plasminogen Activator

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