title: A novel model for evaluating thrombolytic therapy in dogs with ST-elevation myocardial infarction.
abstract: BACKGROUND
  There is still no standard large animal model for evaluating the effectiveness of potential thrombolytic therapies. Here, we aimed to develop a new beagle model with ST-elevation myocardial infarction (STEMI) by injecting autologous emboli with similar components of coronary thrombus.
  
  
  METHODS
  18 male beagles were included and divided into three groups: red embolus group (n = 6), white embolus group (n = 6) or white embolus + rt-PA group (n = 6). Autologous emboli were infused into the mid-distal region of the left anterior descending coronary artery. The composition of embolus was examined by scanning electron microscope (SEM). Coronary angiography was performed to verify the status of embolism. Myocardial infarct size was measured by 2, 3, 5- triphenyltetrazolium chloride (TTC) staining.
  
  
  RESULTS
  Red thrombus was characteristic of loose reticular structure of erythrocytes under SEM, while the white embolus had compacted structure that mainly consisted of a dense mass of fibrin. Coronary angiography showed the recanalization rate was 2/6 in the red embolus group versus 0/6 in the white embolus group in three hours after occlusion. Arrhythmia, resolution of ST-segment elevation and lower T wave on the electrocardiogram appeared in the red embolus group but not in the white embolus group. Another six dogs with white thrombi were treated with rt-PA. Five out of six dogs exhibited coronary recanalization after two hours of therapy, compared to zero dogs without rt-PA treatment. The size of myocardial infarction in rt-PA group reduced significantly compared with white embolus group using TTC staining method.
  
  
  CONCLUSIONS
  The white embolism model was more convenient experimentally and had a higher uniformity, stability and success rate. The major innovation of our study is that we applied fibrin-rich white thrombi to establish beagle model possessing features of clinically observed coronary thrombi in time window of intravenous thrombolysis of STEMI. This model can be used to evaluate new thrombolytic drugs for the treatment of STEMI.
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Cui
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Yuan
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Yang
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Peng
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Liu
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China.
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Wu
authors.affiliation: Center of Clinical Laboratory, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. fwcomd@126.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Animal Experiment Center & Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials, Beijing, 100037, People's Republic of China. tangyue1226@vip.sina.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000818:Animals; D002482:Cellulose; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D004912:Erythrocytes; D005337:Fibrin; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D005337:Fibrin; D002482:Cellulose; D010959:Tissue Plasminogen Activator
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