Journal Article

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

Casper, Eman Ahmed, Khorshid, Ramy, Gamal, Mohamed A., Fahmy, Sarah F., Wakeel, Lamia El, Sabri, Nagwa A.

2025

Overview

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.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Aged / Biochemistry / Biomarkers / Biomarkers - blood / Biomedical and Life Sciences / Biomedicine / Blood pressure / Bypass / Cancer Research / Cardiac patients / Care and treatment / Cell Biology / Clopidogrel / Coronary artery / Coronary artery bypass / Coronary Artery Bypass - adverse effects / Coronary vessels / Female / Grafting / Heart surgery / Humans / Inflammation / Inflammation - drug therapy / Injuries / Interleukin 6 / Interleukin-6 - blood / Ischemia / Male / Melatonin / Melatonin - administration & dosage / Melatonin - therapeutic use / Middle Aged / Myocardial Reperfusion Injury - drug therapy / NF-kappa B - blood / NF-kappa B - metabolism / NF-κB protein / Oncology / Patient outcomes / Patients / Placebos / Prospective Studies / Reperfusion / Side effects / Standard of care / Statistical analysis / Surgery / Thoracic surgery / Thorax / Treatment Outcome / Troponin I - blood / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Virology