Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including
obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of
acute coronary syndromes and
myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during
heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of
ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of
ischemia-reperfusion is not completely understood, there is considerable evidence implicating
reactive oxygen species (ROS) as an initial cause of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize
proteins to inactive states and cause
DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of
ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-
ischemia, with recent studies supporting a role for them in
infarction,
necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following
ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous
free radical scavengers such as
superoxide dismutase,
catalase, and the
glutathione peroxidase and
thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various
antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from
ischemia-reperfusion injury. This review summarises the role of myocardial
antioxidant enzymes in
ischemia-reperfusion injury, particularly the
glutathione peroxidase (GPX) and the
thioredoxin reductase (TxnRed) systems. GPX and TxnRed are
selenocysteine dependent
enzymes, and their activity is known to be dependent upon an adequate supply of dietary
selenium. Moreover, various studies suggest that the supply of
selenium as a cofactor also regulates gene expression of these
selenoproteins. As such, dietary
selenium supplementation may provide a safe and convenient method for increasing
antioxidant protection in aged individuals, particularly those at risk of
ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial
hypoxia.