Table 1.
The effect of melatonin supplementation on cardiac diseases: animal studies.
| Animal model | Genre and strain | Age or weight | Sample size | Melatonin administration | Effect | References | ||
|---|---|---|---|---|---|---|---|---|
| Dose | Mode and duration | |||||||
| Arrhythmias | Myocardial I/R Arrhythmias in normal rats (in vitro) |
Male Sprague-Dawley rats | 280–320 g | n = 10/group | 1, 10, 50 μM | In the perfusate either during entire experiment or 2 min before reperfusion | Cardioprotection | Tan et al., 1998 |
| Myocardial I/R Arrhythmias normal rats (ex vivo) |
Male Wistar rats | 280–350 g | n = 6/group | 1 or 10 mg/kg | I.P. at 10 min before ischemia | Cardioprotection | Lagneux et al., 2000 | |
| Myocardial I/R Arrhythmias in pinealectomized rats (in vivo) |
Male Wistar rats | 150–200 g | n = 16/group | 0.4 / 4 mg/kg | I.V. at 10 min before ischemia or just prior to reperfusion | Cardioprotection No effect in non-pinealectomized rats | Sahna et al., 2002 | |
| Myocardial I/R Arrhythmias in spontaneously hypertensive and fructose-induced metabolic syndrome rats (ex vivo) |
Male Wistar Kyoto (WKY) rats | 12 wk | n = 12/group | 50 μM | In the perfusate at reperfusion (15 min regional ischemia) | Cardioprotection | Diez et al., 2013 | |
| Myocardial I/R injury | Myocardial I/R in normal rabbits (in vivo) | Male New Zealand white rabbits | 2.2–3.2 kg | n = 8/group | 10 mg/kg/day | I.V. at 10 min before ischemia and 15 min before reperfusion | No effect | Dave et al., 1998 |
| Myocardial I/R injury in normal rats (ex vivo) | Male Wistar rats | 250–300 g | n = 6/group | 50 μM | In the perfusate for 15 min before ischemia and during 2h of reperfusion | Cardioprotection | Petrosillo et al., 2009 | |
| Myocardial I/R injury in diet induced obesity rats (ex vivo) |
Male Wistar rats | 4 wk 180–220 g |
n = 6/group | 4 mg/kg/ day | Oral for 6 or 3 wk | Cardioprotection | Nduhirabandi et al., 2014 | |
| Myocardial I/R injury in normal rats and mice (in vivo and ex vivo) |
Male Wistar rats and C57BL6 mice | 240–300 g (Rats) 12–16 wk (Mice) | n > 5/group | 75 ng/L | Oral for 2 wk before I/R injury | Cardioprotection | Lamont et al., 2015 | |
| Myocardial I/R injury in normal mice (ex vivo) | Male C57BL mice | 12–16 wk | n = 6/group | 75 ng/L | In the perfusate before ischemia |
Cardioprotection | Nduhirabandi et al., 2016 | |
| Myocardial I/R injury in normal rats (ex vivo) | Male Wistar rats | 240–300 g | n = 36 (5–7/group) | 75 ng/L | In the perfusate before ischemia |
Cardioprotection | Nduhirabandi et al., 2016 | |
| Myocardial I/R injury in a closed-chest porcine model in normal pigs (in vivo) | Female Danish Landrace pigs | Not given | n = 20 | 5 mg/kg (0.4 mg/mL) |
IV infusion at 5 min before reperfusion for 30 min and intracoronary infusion at 1 min to reperfusion for 2 min | No effect | Ekelof et al., 2016 | |
| Myocardial I/R injury in hyper- glycaemic rats (in vivo) | Male Sprague-Dawley rats | 200–220 g | n = 6/group | 10 mg/kg/day | I.V. at 5 min before and during ischemia and 4 h reperfusion | Cardioprotection | Yu et al., 2017a | |
| Myocardial I/R injury in diabetic rats (in vivo) | Male Sprague-Dawley rats | 8 wk 180–220 g |
n = 6/group | 10 mg/kg/day | Oral for 5 days and I.P at 10 min before reperfusion | Cardioprotection | Yu et al., 2017b | |
| Myocardial I/R injury in normal fed mice (in vivo) | Male C57BL/6 mice | 8 wk 20–22 g | n = 8 group | 20 mg/kg/day | I.P at 10 min before reperfusion. | Cardioprotection | Zhai et al., 2017a | |
| Heart failure | Myocardial infarction-induced heart failure in normal rats (in vivo) | Male Wistar albino rats | 200–250 g | n = 6/group | 10 mg/kg/day | I.P for 4 wk | Cardioprotection | Sehirli et al., 2013 |
| Post-infarction cardiac remodeling and dysfunction in normal mice (in vivo) | Male C57BL Mice | 8–12 wk | n = 6/group | 20 mg/kg/day | Oral for 1 wk before MI | Cardioprotection | Hu et al., 2017 | |
| Isoproterenol-induced myocardial infarction in normal rats (in vivo) | Male Sprague-Dawley rats | 10 wk 175–225 g | n = 6/group | 10 mg/kg/day | I.P. for 1 wk | Cardioprotection | Patel et al., 2010 | |
| Isoproterenol-induced heart failure in normal rats (in vivo) | Male Wistar rats | 12 wk | n = 12/group | 10 mg/kg/day | Oral for 2 or 4 wk | Cardioprotection But no effect on LV or RV hypertrophy | Simko et al., 2014a | |
| Pathological cardiac hypertrophy induced by transverse aortic constriction in normal mice (in vivo) | Male C57BL/6 mice | 20–25g 8–10 wk |
n = 85 (n = 10–40/group) | 20 mg/kg/day | Oral for 4 or 8 wk | Cardioprotection | Zhai et al., 2017b | |
| Pulmonary hypertension | Chronic hypoxia-induced RV hypertrophy and pulmonary hypertension (in vivo) |
Male Sprague–Dawley rats | 200–250g | n = 7/group | 15 mg/kg/day | I.P. morning /wk prior to hypoxic and 4 wk hypoxia | Cardioprotection | Jin et al., 2014 |
| Monocrotaline-induced pulmonary hypertensive rats (ex vivo heart perfusion) | Male Long Evans rats |
150–175g | n = 6/group | 75 ng/L 6 mg/kg/day | Oral for 2 or 4 wk | Cardioprotection | Maarman et al., 2015 | |
| Hypertensive heart disease | Continuous light-induced hypertensive rats (6 wk) (in vivo) |
Male Wistar rats | 12 wk | n = 10/group | 10 mg/kg/day | Oral for 6 wk | Cardioprotection But no effect on LV hypertrophy | Simko et al., 2014b |
I/R, ischemia reperfusion; MI, myocardial infarction; LV, left ventricular; RV, right ventricular; IV, intravenous injection; IP, intraperitoneal injection; wk, week.