title: Efficacy of a new mutated recombinant tissue-type plasminogen activator in beagles with acute coronary artery thrombi.
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.
  
  
  CONCLUSIONS
  rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
authors.forename: Lin-Bo
authors.initials: LB
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China (Bai J, Jiang H, Zhao DD, Hu HY) ; College of Life Science, Wuhan University, Wuhan 430072, China (Ye LB).
authors.forename: Hong-Yao
authors.initials: HY
authors.lastname: Hu
keywords: D-dime; Platelet aggregation; RtPA; Thrombi; Urokinase