Assaf Malka1, David Meerkin, Yaron D Barac, Eytan Malits, Noa Bachner-Hinenzon, Shemy Carasso, Offir Ertracht, Itzchak Angel, Rona Shofti, Moussa Youdim, Zaid Abassi, Ofer Binah. 1. *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.
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.
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: Stephanie L Thorn; Shayne C Barlow; Attila Feher; Mitchel R Stacy; Heather Doviak; Julia Jacobs; Kia Zellars; Jennifer M Renaud; Ran Klein; Robert A deKemp; Aarif Y Khakoo; TaeWeon Lee; Francis G Spinale; Albert J Sinusas Journal: Circ Cardiovasc Imaging Date: 2019-11-11 Impact factor: 7.792
Authors: Csaba Mátyás; Attila Kovács; Balázs Tamás Németh; Attila Oláh; Szilveszter Braun; Márton Tokodi; Bálint András Barta; Kálmán Benke; Mihály Ruppert; Bálint Károly Lakatos; Béla Merkely; Tamás Radovits Journal: Cardiovasc Diabetol Date: 2018-01-16 Impact factor: 9.951