Malka Assaf, Ertracht Offir, Bachner-Hinenzon Noa, Reiter Irina, Binah Ofer
Faculty of Medicine in the Galilee Bar-Ilan University Safed Israel.
Eliachar Research Laboratory Galilee Medical Center Nahariya Israel.
Pharmacol Res Perspect. 2016 Nov 22;4(6):e00272. doi: 10.1002/prp2.272. eCollection 2016 Dec.
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.
急性心肌梗死（MI）后，早期成功的再灌注是减少梗死面积和改善临床结局的最有效策略。然而，缺血区域血流的立即恢复会导致心肌损伤，即“再灌注损伤”。尽管我们之前报道过TVP1022（雷沙吉兰的S-异构体，一种FDA批准的抗帕金森病药物）可在大鼠缺血再灌注（I/R）24小时后减小梗死面积，但在本研究中，我们调查了I/R 14天后TVP1022的慢性心脏保护功效。为模拟急性心肌梗死后再灌注治疗的临床情况，我们采用了左前降支动脉闭塞30分钟后再灌注并随访14天的大鼠模型。TVP1022最初在闭塞后-再灌注前给药，随后每日进行长期给药。使用常规和先进的超声心动图方法评估心脏功能和重塑，通过Millar Mikro-Tip导管进行血流动力学测量，并采用组织病理学技术。TVP1022给药显著减少了重塑过程，表现为左心室扩大和心肌肥大的减轻（在整个心脏和细胞水平均如此）。此外，TVP1022抑制了心脏纤维化并降低了心室BNP水平。在功能上，TVP1022治疗保留了心脏壁运动。具体而言，TVP1022显著改善了超声心动图和大多数直接血流动力学测量结果。总体而言，这些发现表明TVP1022在该I/R模型中对I/R损伤和心肌梗死后重塑具有显著的心脏保护作用。
