title: The cardioprotective efficacy of TVP1022 against ischemia/reperfusion injury and cardiac remodeling in rats.
abstract: Following acute myocardial infarction (MI), early and successful reperfusion is the most effective strategy for reducing infarct size and improving the clinical outcome. However, immediate restoration of blood flow to the ischemic zone results in myocardial damage, defined as "reperfusion-injury". Whereas we previously reported that TVP1022 (the S-isomer of rasagiline, FDA-approved anti-Parkinson drug) decreased infarct size 24 h post ischemia reperfusion (I/R) in rats, in this study we investigated the chronic cardioprotective efficacy of TVP1022 14 days post-I/R. To simulate the clinical settings of acute MI followed by reperfusion therapy, we employed a rat model of left anterior descending artery occlusion for 30 min followed by reperfusion and a follow-up for 14 days. TVP1022 was initially administered postocclusion-prereperfusion, followed by chronic daily administrations. Cardiac performance and remodeling were evaluated using customary and advanced echocardiographic methods, hemodynamic measurements by Millar Mikro-Tip®catheter, and histopathological techniques. TVP1022 administration markedly decreased the remodeling process as illustrated by attenuation of left ventricular enlargement and cardiac hypertrophy (both at the whole heart and the cellular level). Furthermore, TVP1022 inhibited cardiac fibrosis and reduced ventricular BNP levels. Functionally, TVP1022 treatment preserved cardiac wall motion. Specifically, the echocardiographic and most of the direct hemodynamic measures were pronouncedly improved by TVP1022. Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R model.
authors.affiliation: Faculty of Medicine in the Galilee Bar-Ilan University Safed Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Malka
authors.affiliation: Eliachar Research Laboratory Galilee Medical Center Nahariya Israel.
authors.forename: Offir
authors.initials: O
authors.lastname: Ertracht
authors.affiliation: Migal Galilee Technology Center Department of Computational Science and Bioinformatics Kiryat, Shmona Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Bachner-Hinenzon
authors.affiliation: Department of Physiology, Biophysics and Systems Biology the Rappaport Faculty of Medicine and Research Institute Technion, Haifa Israel.
authors.forename: Irina
authors.initials: I
authors.lastname: Reiter
authors.affiliation: Department of Physiology, Biophysics and Systems Biology the Rappaport Faculty of Medicine and Research Institute Technion, Haifa Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
keywords: Cardioprotection; TVP1022; ischemia/reperfusion; myocardial infarction; remodeling