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.