Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010;1(2):126-31.

Efficacy of a new mutated recombinant tissue-type plasminogen activator in beagles with acute coronary artery thrombi

Jing Bai  1 , Lin-Bo Ye  1 , Hong Jiang  1 , Dong-Dong Zhao  1 , Hong-Yao Hu  1
Affiliations

Efficacy of a new mutated recombinant tissue-type plasminogen activator in beagles with acute coronary artery thrombi

Jing Bai et al. World J Emerg Med. 2010.

Abstract

Background: Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy.

Methods: A total of 30 adult beagles were equally divided into 5 groups after thrombi: vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy.

Results: In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)% in the medium-dose rtPAm group and (0.7+0.4)% in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group.

Conclusion: rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.

Keywords: D-dime; Platelet aggregation; RtPA; Thrombi; Urokinase.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: The authors have no competing interests relevant to the present study.

Figures

Figure 1
Figure 1
The changes of PT before and after administration of the agent in each group. No significant change was observed in the prothrombin time (PT) before and after the administration in all groups, indicating that there was no change in coagulation function.
Figure 2
Figure 2
The changes of APTT levels before and after administration of the agent in each group. No significant changes were observed in the activated partial thromboplastin time (APTT) in all groups, indicating that there was no change in coagulation function before and after administration.
Figure 3
Figure 3
The changes of Fg (mg/ml) before and after administration of the agent in each group. No significant changes were observed in the concentration of fibrinogen (Fg) during the test for each group, suggesting that the concentration of rtPAm has no notable influence on the coagulation system and fibrinolysis.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Medved L, Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin. Thromb Haemost. 2003;89:409–419. - PubMed
    1. Liang JF, Li YT, Yang VC. The potential machanisms for the effect of heparin on tissue plasminogen activator-mediated plasminogen activation. Thromb Res. 2000;97:349–358. - PubMed
    1. Li BZ, Zheng H, Ye LB, et al. The Comparison of the thrombolytics activity between recombinant tPA and its mutated form. Wuhan Univ (Nat Sci Ed) 2004;50:765–768.
    1. Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, et al. Early phase acute myocardial infarct size quantification: Validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J. 1981;101:593–600. - PubMed
    1. Clauss A. Rapid physiological coagulation method in determination of fibrinogen. Acta Haematol. 1957;17:237–246. - PubMed

LinkOut - more resources