0161: The neuroprotective agent rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

Abstract

Rasagiline, (R) mesylate (N-propargyl-1 (R)-aminoindan) is a selective, potent irreversible inhibitor of MAO-B with neuroprotective and anti-apoptotic properties. We investigated whether R could provide cardioprotection in a 6 month Wistar male rat model (350-400gr) undergoing experimental Myocardial Infarction (MI). MI was induced surgically by a permanent ligation of the left anterior descending coronary artery. We included 3 experimental groups: R (n=10), Control (C) (n=10), and sham-operated (S) (n=10). R was administered daily (2 mg/kg i.p.) for 4 weeks, beginning 24 hours after MI induction. Group C received normal saline 0.9%, i.p. Cardiac function was assessed by two-dimensional targeted M-mode echocardiography (Vivid 7, 13MHz), at baseline, 14 and 28 days post MI. Estimation of cardiac remodeling and cardiomyocyte damage was performed by immuno-fluorescent microscopy analysis. Baseline measurements were similar in all groups. Group R showed less FS (%) deterioration vs group C at 14 (31.4±2.1 vs 22.3±2.0, p<0.0001) and 28 days (31.6±2.3vs19.6±1.8, p<0.0001). Immuno-fluorescent microscopy analysis of the infract border zone indicated reduced collagen I staining in group R (n=3) rats compared to group C (n=3) and less cardiomyocyte degeneration as indicated by b-catenin and desmin staining. Also, apoptosis (TUNEL) was reduced by 65% in the border zone and 58% in the remote region of R treated animals. Importantly, scar size did not differ among the two groups. Our study showed attenuation in cardiac remodelling after MI as presented by better systolic function in Rasagiline mesylate (a commonly used neurological drug) treated rats accompanied by less border zone fibrosis and cardiomyocyte degeneration indicating a beneficial effect in the post-MI period.