title: TVP1022: A Novel Cardioprotective Drug Attenuates Left Ventricular Remodeling After Ischemia/Reperfusion in Pigs.
abstract: BACKGROUND
  The current cornerstone treatment of myocardial infarction (MI) is restoration of coronary blood flow by means of thrombolytic therapy or primary percutaneous coronary intervention. However, reperfusion of ischemic myocardium can actually provoke tissue damage, defined as "ischemia-reperfusion (I/R) injury." TVP1022 [the S-isomer of rasagiline (Azilect), FDA-approved anti-Parkinson's drug] was found to exert cardioprotective activities against various cardiac insults, such as chronic heart failure and I/R, in rat models. Therefore, we tested the hypothesis that TVP1022 will provide cardioprotection against I/R injury and post-MI remodeling in a pig model.
  
  
  METHODS
  For inducing MI, we used an I/R model of midleft anterior descending artery occlusion for 90 minutes followed by follow-up for 8 weeks in 18 farm pigs (9 pigs in each group, MI + TVP1022 or MI + Vehicle). Echocardiographic measurements were performed and cardiac scar size was calculated using histopathological methods. For fibrosis evaluation, we measured the interstitial collagen volume fraction in the remote noninfarcted tissue.
  
  
  RESULTS
  TVP1022 administration significantly decreased cardiac scar size, attenuated left ventricular dilation, and improved cardiac function assessed by segmental circumferential strain analysis. Furthermore, TVP1022 significantly reduced myocardial fibrosis 8 weeks post-MI.
  
  
  CONCLUSIONS
  Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R pig model.
authors.affiliation: *Department of Physiology, Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, Israel; †Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel; ‡The Cardiothoracic Department, Rabin Medical Center, Petach Tikva, Israel; §CardiAmit LTD, Haifa, Israel; ¶Analyze IT Research Institute, Tuval, Israel; ‖Department of Cardiology, Rambam Health Care Campus, Haifa, Israel; **Eliachar Research Laboratory, Galilee Medical Center, Nahariya, Israel; ††Angel Pharmaceutical Consulting & Technologies Ltd, Nes Ziona, Israel; ‡‡Rappaport Faculty of Medicine and Research Institute, Technion, Haifa, Israel; and §§Abital Pharma Pipeline Ltd, Tel Aviv, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Malka
authors.forename: David
authors.initials: D
authors.lastname: Meerkin
authors.forename: Yaron D
authors.initials: YD
authors.lastname: Barac
authors.forename: Eytan
authors.initials: E
authors.lastname: Malits
authors.forename: Noa
authors.initials: N
authors.lastname: Bachner-Hinenzon
authors.forename: Shemy
authors.initials: S
authors.lastname: Carasso
authors.forename: Offir
authors.initials: O
authors.lastname: Ertracht
authors.forename: Itzchak
authors.initials: I
authors.lastname: Angel
authors.forename: Rona
authors.initials: R
authors.lastname: Shofti
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdim
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D034421:Sus scrofa; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D007189:Indans; C031967:rasagiline