Abstract:
:Currently, the effects of the thrombolytic drugs are tested in vivo in dog or rabbit models that require a relatively large amount of the drug. The goal of the present study was to describe a new model that would allow one to test the in vivo thrombolytic effect of drugs with a limited amount of compound. For this purpose, we have induced a pulmonary embolus in anesthetized rats by injecting I125 radiolabeled clots into the venous circulation and we have measured the lysis of these clots occurring either spontaneously or induced by increasing doses of wild-type tissue plasminogen activator (tPA) (from 0.125 to 2 mg/kg i.v.) or by streptokinase (750,000 I.U./kg i.v.) or urokinase (750,000 I.U./kg i.v.). In the plasma of these rats, we have also measured the plasminogen activation activity of tPA as well as the concentrations of plasminogen, fibrinogen, and alpha 2-antiplasmin. Spontaneously, there was a time dependent thrombolysis (33%/h) that could be partially inhibited by aprotinin. Wild-type tPA induced a dose-related thrombolysis with a limited decrease of plasma fibrinogen concentration with doses over 0.25 mg/kg. Streptokinase and to a smaller extent urokinase induced a larger hemostatic breakdown (as indicated by systemic fibrinogenolysis, plasminogen activation, and alpha 2-antiplasmin consumption). We conclude that the rat pulmonary embolus model is suitable for testing the thrombolytic efficacy, potency, and the fibrin specificity of thrombolytic drugs and requires a smaller amount of drug than the previously described in vivo models.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Clozel JP,Holvoet P,Tschopp Tdoi
10.1097/00005344-198811000-00004subject
Has Abstractpub_date
1988-01-01 00:00:00pages
520-5issue
5eissn
0160-2446issn
1533-4023journal_volume
12pub_type
杂志文章abstract::Intracellular calcium ([Ca]i) overload on reperfusion may be one of the mechanisms responsible for ischemia-induced regional myocardial dysfunction. Because inhibiting the Na-H exchanger (NHE) limits intracellular sodium ([Na]i) and subsequent [Ca]i accumulation, we hypothesized that NHE inhibition would attenuate reg...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198203000-00015
更新日期:1982-03-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198009000-00007
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199805000-00009
更新日期:1998-05-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812000-00013
更新日期:1988-12-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198911000-00002
更新日期:1989-11-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1991-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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更新日期:1990-06-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:1991-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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