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.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Coronary Artery Bypass Grafting
• Intervention / Treatment: Dietary supplement: Melatonin; Other: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: eman A. casper, masters; Phone Number: 0201068731483; Email: drcasper912009@hotmail.com
• Study Contact Backup: Name: sara M. Farid, PhD; Phone Number: 01001232067; Email: sarah.farid@pharma.asu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Melatonin group; Melatonin Group (n=11) patients will receive 60 mg/day Melatonin capsule (M1) from the day five before surgery.	Dietary supplement: Melatonin; patients in the melatonin group will receive 60 mg/day Melatonin capsule (M1) from the day five before surgery.
Placebo Comparator: Control group; 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.	Other: placebo; patients will receive capsules of the same size and color

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nuclear factor-kB (NF-κB)	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	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
interleukin 6 il-6	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.	24 hours
Tumor necrosis factor alpha TNF-α	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.	24 hours
cardiac troponins	cardiac marker	24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVEF%	left ventricular ejection fraction	24 hours
Safety (Adverse effects from melatonin)	Safety of melatonin	5 days
hospital length of stay	Duration of staying in hospital	5-7 days
ICU length of stay	Duration of staying in ICU	2-3 days

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: eman A. casper, masters, Ain Shams University , faculty of pharmacy

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: melatonin; CABG; inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Postoperative Complications; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Reperfusion Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: PHCL91

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No