title: Melatonin reduces cardiac remodeling and improves survival in rats with isoproterenol-induced heart failure.
abstract: Melatonin was previously shown to reduce blood pressure and left ventricular (LV) remodeling in several models of experimental heart damage. This study investigated whether melatonin prevents LV remodeling and improves survival in isoproterenol-induced heart failure. In the first experiment, four groups of 3-month-old male Wistar rats (12 per group) were treated for 2 wk as follows: controls, rats treated with melatonin (10 mg/kg/day) (M), rats treated with isoproterenol (5 mg/kg/day intraperitoneally the second week) (Iso), and rats treated with melatonin (2 wk) and isoproterenol (the second week) in corresponding doses (IsoM). In the second experiment, 30 rats were treated with isoproterenol and 30 rats with isoproterenol plus melatonin for a period of 28 days and their mortality was investigated. Isoproterenol-induced heart failure with hypertrophy of the left and right ventricles (LV, RV), lowered systolic blood pressure (SBP) and elevated pulmonary congestion. Fibrotic rebuilding was accompanied by alterations of tubulin level in the LV and oxidative stress development. Melatonin failed to reduce the weight of the LV or RV; however, it curtailed the weight of the lungs and attenuated the decline in SBP. Moreover, melatonin decreased the level of oxidative stress and of insoluble and total collagen and partly prevented the beta-tubulin alteration in the LV. Most importantly, melatonin reduced mortality and prolonged the average survival time. In conclusion, melatonin exerts cardioprotective effects and improves outcome in a model of isoproterenol-induced heart damage. The antiremodeling effect of melatonin may be of potential benefit in patients with heart failure.
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic; 3rd Clinic of Medicine, School of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic; Center of Excellence NOREG, Bratislava, Slovak Republic.
authors.forename: Fedor
authors.initials: F
authors.lastname: Simko
authors.forename: Kristina Repova
authors.initials: KR
authors.lastname: Bednarova
authors.forename: Kristina
authors.initials: K
authors.lastname: Krajcirovicova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Hrenak
authors.forename: Peter
authors.initials: P
authors.lastname: Celec
authors.forename: Natalia
authors.initials: N
authors.lastname: Kamodyova
authors.forename: Lucia
authors.initials: L
authors.lastname: Gajdosechova
authors.forename: Stefan
authors.initials: S
authors.lastname: Zorad
authors.forename: Michaela
authors.initials: M
authors.lastname: Adamcova
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008550:Melatonin; D007545:Isoproterenol
keywords: fibrosis; heart failure; heart hypertrophy; isoproterenol; melatonin; mortality; remodeling