Melatonin Impact on the Outcomes of Myocardial Ischemia/Reperfusion Injury During Coronary Artery Bypass Grafting Surgery

Melatonin Impact on the Outcomes of Myocardial Ischemia/Reperfusion Injury During Coronary Artery Bypass Grafting Surgery

The Effect of Melatonin on the Outcomes of Myocardial Ischemia/Reperfusion Injury During Coronary Artery Bypass Grafting Surgery

The ischemia/reperfusion (I/R) injury of the myocardium initiates a variety and complex sets of inflammatory reactions that may both exaggerate local injury as well as provoke injury of distant organ function . I/R injuries are the main causes of heart failure, morbidity, and mortality after cardiac surgery such as coronary artery bypass graft (CABG surgery) . The reactive oxygen species are believed to be excessively elevated during coronary artery bypass surgery (CABG) due to compromised free radical scavenging mechanism in the myocardium that can make myocardium highly susceptible to oxidative stress and inflammation and result in reperfusion injury . Melatonin and its metabolites protect against inflammation by regulating several inflammatory cytokines. Additionally, melatonin is a free radical scavenger and an antioxidant agent. the current study is designed to investigate the protective effects of melatonin against myocardial I/R injury in patients undergoing coronary artery bypass grafting (CABG) surgery.

Myocardial ischemia is a situation where there is an inadequate blood and oxygen supply to the heart muscles due to partial or complete obstruction of the coronary arteries, predisposing the affected cardiac muscle to death. Hence, restoration of blood supply is critical to reestablish myocardial reperfusion. The ischemia/reperfusion (I/R) injury of the myocardium initiates a variety and complex sets of inflammatory reactions that may both exaggerate local injury as well as provoke injury of distant organ function . I/R injuries are the main causes of heart failure, morbidity, and mortality after cardiac surgery such as coronary artery bypass graft (CABG surgery) . The reactive oxygen species are believed to be excessively elevated during coronary artery bypass surgery (CABG) due to compromised free radical scavenging mechanism in the myocardium that can make myocardium highly susceptible to oxidative stress and inflammation and result in reperfusion injury . Strategies to improve the CABG related complications are much needed to augment the positive outcomes in the post-operative surviving patients. There are various therapeutic approaches to decrease or ameliorate myocardial I/R injury, these include reperfusion controlling, cardioprotective events and management via various interventions. Melatonin (N-acetyl 5-methoxy-tryptamine) is mainly secreted by the pineal gland to regulate sleep. Since 1993 when melatonin was first reported, a wide range of melatonin functions have been directly confirmed by multiple scientific studies . Melatonin and its metabolites protect against inflammation by regulating several inflammatory cytokines. Additionally, melatonin is a free radical scavenger and an antioxidant agent. Early studies have shown that melatonin exerts beneficial effects in the context of renal I/R, myocardial I/R, and hepatic I/R. The ability to protect against I/R injury may relate to the functions of melatonin as both an anti-inflammatory and an antioxidant agent . Some authors show an anti-apoptotic action of melatonin in different organs of the body, such as thymus, kidney, brain and liver . the current study is designed to investigate the protective effects of melatonin against myocardial I/R injury in patients undergoing coronary artery bypass grafting (CABG) surgery.

Melatonin Group (n=11) patients will receive 60 mg/day Melatonin capsule (M1) from the day five before surgery.

Control group (n=11) patients will receive placebos with the same appearances and packaging at the same dose and time as those in the melatonin group.

patients in the melatonin group will receive 60 mg/day Melatonin capsule (M1) from the day five before surgery.

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor that is involved in inflammatory and immune responses, as well as in regulation of expression of many other genes related to cell survival, proliferation, and differentiation

Interleukin-6 is a widely used cytokine that causes inflammation and oxidative stress, which would further result in cardiac and cerebral injury. The increased expression of interleukin-6 is closely related to atherosclerosis, myocardial infarction, heart failure and ischemic stroke. It is a key risk factor for these diseases by triggering inflammatory reaction and inducing other molecules release.

Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated heart diseases.

Inclusion Criteria: Patients who will undergo elective CABG, ready to participate in the study and can be reached by phone Exclusion Criteria: • Patients who will require urgent surgery and won't have adequate time to take medications for 5 days, Re-operative patients (CABG), Off-pump CABG, Patients who have concomitant renal failure, Patients with severe respiratory problems. Patients with previous stroke or significant cerebrovascular disease, Patients with hepatitis b,c and HIV. Inflammatory disease ex. Rheumatoid arthritis, psoriasis…, Patients with ejection fraction (EF%) lower than 40%, Patients undergo CABG surgery with simultaneous heart valve repair or replacement, resection of a ventricular aneurysm, or other operations. Pregnancy and lactation.