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Background: Remodeling of remote healthy myocardium follows a myocardial infarction (MI). An important involving mechanism is formation of reactive oxygen species (ROS). The antidepressant, paroxetine, has the ability to bind ROS-molecules. We aimed to investigate the effect of paroxetine on remodeling of the left ventricle (LV) in rats following a MI.
Methods: In 32 Wistar rats, MI was induced by a 30-minute ligation of the left anterior descending artery followed by 7 or 28 days reperfusion in the short and long term follow-up period, respectively. During a 28 days follow-up period, cardiac remodeling in the rats (n=20) was evaluated with a dedicated high frequency rat ultrasound system and a 9.4 tesla rat MR-scanner. The rats were electro physiologically evaluated for their susceptibility to arrhythmias before removal of the heart. Myocyte cross sectional area, extent of fibrosis and percentage of myofibroblasts were evaluated histologically. ROS-production in the hearts was evaluated with the fluorescent stain dihydroethidium after 7 days in a separate group (n=12).
Results: Diastolic LV volume, evaluated by MRI (417.4±60.03μL vs. 510.7±63.90μL, p<0.05) and echocardiography (515.4±80.31μL vs. 596.2±82.90μL, p<0.05), as well as diastolic LV inner diameter evaluated with echocardiography (7.238±0.55mm vs. 8.101±0.69mm, p<0.05) were significantly lower in paroxetine treated animals than in controls at the end of the follow-up period. Furthermore, myocyte cross sectional area was significantly reduced in the paroxetine group compared with the control group (276.9 ± 26.42mm3 vs 354.1 ± 22.69mm3, p<0.05) and ROS-production was reduced in the remote myocardium (0.415±0.19 normalized to controls, p<0.05). However, we observed no differences in the extent of fibrosis or percentage of myofibroblasts, between groups. Lastly, the hearts had decreased susceptibility to arrhythmias (ventricular tachycardia induced in 2/11 vs 6/8 rats, p<0.05).
Conclusions: Paroxetine treatment for four weeks decreases LV remodeling and susceptibility to arrhythmias following MI, possibly through reduced ROS-production.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Novel Imaging and Therapies in Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1200-259
- 2017 American College of Cardiology Foundation