Melatonin ameliorates inflammation and improves outcomes of ischemia/reperfusion injury in patients undergoing coronary artery bypass grafting surgery: a randomized placebo-controlled study

Abstract

To investigate the protective role of high dose melatonin concerning myocardial I/R injury and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG) surgery by evaluating IR/inflammatory biomarkers and clinical outcomes. This was a prospective; randomized; single-blinded placebo-controlled study conducted at cardio-thoracic surgery department of the Academy of the Cardiovascular and Thoracic Surgery, Ain Shams University. Eligible patients were randomly allocated to; melatonin-treated group (MTG) or placebo-treated group (PTG). The MTG (n = 17) received 60 mg/day melatonin capsules daily starting 5 days before surgery in addition to the standard of care. PTG (n = 17) received placebo also 5 days before surgery plus standard of care. The levels of nuclear factor kappa beta (NF-κb) (primary outcome), tumor necrosis factor (TNF-α), cardiac troponins I, and IL-6 levels were all assessed for both groups at five time points: baseline before melatonin or placebo administration (T0), before cross-clamp application(T1), 5 min after cross-clamp removal(T2), 6 h after cross-clamp removal(T3) and 24 h after cross-clamp removal(T4). Blood pressure was assessed at baseline, pre-operative and 24-hours post-operative. The Quality of recovery-40 score (QOR-40) was assessed for both groups on day 4 after surgery. TNF-α levels decreased in the MTG at T1(p = 0.034) versus PTG. At T2(p = 0.005), and T3(p = 0.04), TNF-α significantly increased in PTG versus MTG. Troponins significantly increased in PTG at T3 (p = 0.04) versus MTG. NF-κB levels declined at T1 (p = 0.013) and T2 (p = 0.0001) in MTG compared to PTG. IL-6 significantly increased in PTG versus MTG at T3 (p = 0.04). The QOR-40 score significantly decreased in MTG versus PTG. MTG had statistically significant decrease in DBP compared to the placebo group (p = 0.024). MTG had a statistically significant shorter intubation time than did the placebo group (p = 0.03). Melatonin 60 mg was well-tolerated without any reported side effects. Our findings suggested that melatonin could ameliorate myocardial I/R injury after on-pump CABG and that this outcome was essentially correlated to its antiapoptotic and anti-inflammatory effects. Trial registration: ClinicalTrials.gov registration number NCT05552586, 9/2022.

Keywords: CABG; IL-6; Ischemia/reperfusion injury; Melatonin; NF-kB; TNF-α; Troponins.

Fig. 1

Consort Study flow diagram

Fig. 2

Nuclear factor Kappa Beta (NF-κB), interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and Troponins levels in the plasma of the participants in the Melatonin-treated group (MTG) and placebo-treated group(PTG). A: NF-κB protein expression levels in both groups. B: IL-6 protein expression levels in both groups. C: TNF-α protein expression levels in both groups. D: Cardiac Troponins I protein expression levels in both groups. T0, baseline; T1, pre-cross clamp; T2, after cross clamp removal; T3, 6 h after cross-clamp removal; t4T4, 24 h after cross-clamp removal. *P < 0.05