Background: The current cornerstone treatment of myocardial infarction (MI) is restoration of the coronary blood flow with the use of thrombolytic therapy or primary percutaneous coronary intervention (PCI). However, reperfusion of ischemic cardiac tissue can actually provoke myocardial damage leading to cell death, characterizing "ischemia-reperfusion (I/R) injury". TVP1022 is the S-isomer of rasagiline (Azilect®), FDA-approved anti-Parkinson drug. TVP1022 was found to exert cardioprotective activities against various cardiac insults such as chronic heart failure and Ischemia-reperfusion (I/R) in rat models. Hence, we tested the hypothesis that TVP1022 will provide cardioprotection against I/R injury and post-MI remodeling in a pig model.
Methods: For inducing a MI we utilized an I/R model of mid left anterior descending artery occlusion for 90 minutes followed by reperfusion and follow up period of 8 weeks in 18 farm pigs, (n=9 in each group). Five minutes prior to reperfusion TVP1022 (or saline) was administrated IV. A second dose was given 4 hours later (IV); a third dose was given 24 hours post-MI (IV) and then daily administrations per os. Echocardiographic measurements were performed and scar size was calculated using histopathological methods.
For fibrosis evaluation we measured the interstitial collagen volume fraction (CVF) in the remote non-infarcted tissue.
Results: TVP1022 administration markedly decreased scar size by 36% (P0.005 vs. vehicle), attenuated both left ventricular end diastolic diameter and area enlargement by 22% and 48% respectively (P0.05 vs. vehicle) and maintained cardiac function assessed by segmental circumferential strain analysis. Furthermore, TVP1022 reduced tissue fibrosis in the non-infarcted area by ~23% (from 6.7±0.5% to 5.1±0.4%) (P0.05 vs. vehicle) 8 weeks post-MI.
Conclusion: The ability of TVP1022 to attenuate cardiac damage induced by MI renders this molecule a potential cardio-protective drug for acute coronary syndrome patients.
