The Effect of Melatonin on Ischemia-reperfusion Injury Following Acute Myocardial Infarction

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In Denmark, 12.000 people a year, is struck by acute myocardial infarction. A third of these cannot be saved before treatment is possible.

Despite quick and effective reperfusion of the coronary arteries using PCI (Percutaneous Coronary Intervention) after an acute ST-elevation myocardial infarction, substantial morbidity and mortality remain. Infarct size is an important determinant of the short-and long-term outcome after acute myocardial infarction. The most widely used and most effective proven therapy to limit infarct size is the early reperfusion induced by or PCI.

Although beneficial in terms of myocardial salvage, reperfusion itself may contribute to additional damage of the myocardium; the damage due to the combined processes is known as "ischemia-reperfusion injury". The pathogenesis of myocardial ischemia-reperfusion injury is a multifactorial process involving the interaction of multiple mechanisms. Numerous studies indicate that there are three pivotal factors in the pathogenesis of ischemia-reperfusion injury: elevated oxidative damage, depressed energy metabolism, and altered calcium homeostasis.

Partially reduced species of oxygen, including the superoxide anion radical, hydroxyl radical, and hydrogen peroxide, are generated intracellularly as by-product of oxygen metabolism. These reactive oxygen species cause peroxidation af membrane lipids, denaturation of proteins, and modification of DNA, all of which ultimately can lead to cell death. In mammals, cell damage induced by partially reduced oxygen species can also initiate local inflammatory responses, which then lead to further oxidant-mediated tissue injury.

Melatonin is mainly known for its role as an endogenously produced circadian hormone.

For the last twenty years, increasing evidence has proven melatonin to be a very potent direct and indirect antioxidant.

Recent experimental studies have documented the beneficial effects of melatonin in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion.

Primary hypothesis: Melatonin given to patients undergoing PCI can reduce the myocardial damage sustained by ischemia-reperfusion.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Herlev Hospital
• Treatments: Melatonin

Criteria

Inclusion criteria:

• Adults who are able to give informed consent

• 1 significant coronary occlusion (>2mm) with TIMI 0-1 expected to undergo PCI.

• The occlusion must be ECG-verified with new ST-elevations ≥ 0.2 mV in V2-V3 and/or ≥ 0.1 in the other leads or a new onset left bundle branch block.

• Having onset of symptoms of qualifying AMI and undergo PCI within 6 hours.

• If the patients do not fulfill the ECG inclusion criteria they can still be included if the primary PCI reveals an acute coronary occlusion (>2mm) with TIMI 0-1.

Exclusion criteria:

• Patients with prior myocardial infarction

• more than one significant occlusion

• prehospital thrombolysis

• known history of renal failure

• history of autoimmune diseases

• pregnancy, fertile women or breastfeeding

• severe concurrent illness with reduced short-term prognosis

• pacemaker

• claustrophobia

• cardiogenic shock

• metals in the body

• atrial fibrillation

• BMI ≥ 40.