The Effect of Melatonin on Ischemia-reperfusion Injury Following Acute Myocardial Infarction
Status:
Completed
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
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.