title: Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.
abstract: Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm3, p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark. thomasravnl@clin.au.dk.|Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark. thomasravnl@clin.au.dk.
authors.forename: Thomas Ravn
authors.initials: TR
authors.lastname: Lassen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.
authors.forename: Jan Møller
authors.initials: JM
authors.lastname: Nielsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Johnsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.|MR Research Center, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ringgaard
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.|Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.
authors.forename: Steen Buus
authors.initials: SB
authors.lastname: Kristiansen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004452:Echocardiography; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D017374:Paroxetine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D017374:Paroxetine; D017382:Reactive Oxygen Species; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antioxidant; Heart failure; Myocardial infarction; Paroxetine; Reactive oxygen species; Remodeling