Abstract
Oxidative stress is a major contributor to ischaemia reperfusion injurymediated myocardial infarction. Coronary ischemia deprives the heart muscles of nutrients and oxygen in the areas away from the site of arterial blockage, rendering cardiomyocytes unable to utilise aerobic metabolism to support their energy requirements. Homeostatic intracellular signalling systems, such as the hypoxiainducible factor (HIF) transcription factor cascade, sense the low oxygen environment. This in turn stimulates the upregulation of numerous compensatory mechanisms which are ultimately involved in elevating anaerobic glycolysis and promoting angiogenesis and vascularization. The increased anaerobic metabolism increases the production of lactic acid hence metabolic acidosis. This leads to myocyte death and the expansion of the size of the original area of the infarct. Under normal aerobic conditions, the myocardium generally metabolises relatively high levels of adenosine triphosphates (ATP). In contrast, during ischemia, the shift in energy production to glycolysis results in the inefficient production of ATP and constitutes a pathological feature, and if not reversed early, it may lead to complications such as heart failure and ischemia-induced atrial or ventricular fibrillation. Despite the widespread use of fibrinolytic agents and new types of angioplasty procedures for the treatment of myocardial infarction, often new sets of complications persist. These include the occurrence of extensive tissue injury caused by myocardial reperfusion through the reintroduction of oxygen to the previous ischemic tissues because of the excessive generation of reactive oxygen species (ROSs) and depletion of antioxidants. Widespread production of ROS damages the plasma membrane and stimulates the release of various proinflammatory agents. Several proteins become denatured for example receptors, ionic channels, transporters, or components of transduction pathways through oxidation by ROS. Altered protein structure inhibits their functions leading to the disruption of vital cellular processes. The onset of reperfusion injury is further exacerbated by the activation and infiltration of the infarcted area by polymorphonuclear leukocytes (PMNs). Several studies have identified the release of different leukocyte intracellular factors during PMN activation such as selectins and b2-integrins to be related to the magnitude of tissue damage. Some studies have shown that antagonists for leukocytes intracellular factors such as selectins abrogate PMN activation and reduce the infarct size.
More recent publications have shown that PMN activation is closely linked to the activation of other cells involved in the inflammatory response. For example, during myocardial ischemia–reperfusion injury, it has been shown that the activity of neutrophils is also modulated by lymphocytes and macrophages. This chapter summarises the interaction between oxidative stress, activation of different leukocytes and the release of factors involved in the generation of reperfusion injury.