If a coronary occlusion long enough to produce a myocardial infarction is preceded by one or more brief periods of occlusion, the infarct size is reduced with respect to the area at risk. Also the ischaemia reperfusion injury is remarkably reduced. Such effects form the ischaemic preconditioning. Ischaemia-reperfusion injury is attributed to a Ca2+ overload of the myocardial fibres together with an inadequate resynthesis of ATP, a loss of membrane phospholipids and a release of free oxygen radicals. The inadequate resynthesis of ATP is responsible for an increased concentration of nucleosides and purinic bases with swelling of the myocardial fibres. The cell Ca2+ overload depends on a reduced activity of the ionic pumps caused by the oxygen lack during ischaemia. During reperfusion the vascular endothelial cells of the previously ischaemic area release free oxygen radicals in response to the activity of the xanthine-oxidase on hypoxanthine produced by the ischaemic myocardium. This initial release of oxygen radicals is responsible for the adhesion of neutrophils to the endothelium. After adhesion also the neutrophils release free radicals due to the activity of NADPH-oxidase on molecular oxygen. Myocardial, neural and endothelial mechanisms account for the protective effect of preconditioning. Myocardial mechanisms include the release of adenosine as well as of antioxidant enzymes. Adenosine, which activates protein-kinase C, favours the phosphorylation of a protective protein, whereas the antioxidant enzymes impair the activity of the free oxygen radicals. Preconditioning may also involve the synthesis of a heat shock protein. Neural mechanisms are represented by a reduced release of noradrenaline from the sympathetic nerve endings and a reduced sensitivity of myocardium to noradrenaline. Finally, vascular endothelial cells take part in preconditioning by means of an increased production of nitric oxide which seems to exert a protection against arrhythmias.
Mechanisms of ischemic preconditioning: relation with ischemia-reperfusion injury
PAGLIARO, Pasquale;LOSANO, Giovanni
1997-01-01
Abstract
If a coronary occlusion long enough to produce a myocardial infarction is preceded by one or more brief periods of occlusion, the infarct size is reduced with respect to the area at risk. Also the ischaemia reperfusion injury is remarkably reduced. Such effects form the ischaemic preconditioning. Ischaemia-reperfusion injury is attributed to a Ca2+ overload of the myocardial fibres together with an inadequate resynthesis of ATP, a loss of membrane phospholipids and a release of free oxygen radicals. The inadequate resynthesis of ATP is responsible for an increased concentration of nucleosides and purinic bases with swelling of the myocardial fibres. The cell Ca2+ overload depends on a reduced activity of the ionic pumps caused by the oxygen lack during ischaemia. During reperfusion the vascular endothelial cells of the previously ischaemic area release free oxygen radicals in response to the activity of the xanthine-oxidase on hypoxanthine produced by the ischaemic myocardium. This initial release of oxygen radicals is responsible for the adhesion of neutrophils to the endothelium. After adhesion also the neutrophils release free radicals due to the activity of NADPH-oxidase on molecular oxygen. Myocardial, neural and endothelial mechanisms account for the protective effect of preconditioning. Myocardial mechanisms include the release of adenosine as well as of antioxidant enzymes. Adenosine, which activates protein-kinase C, favours the phosphorylation of a protective protein, whereas the antioxidant enzymes impair the activity of the free oxygen radicals. Preconditioning may also involve the synthesis of a heat shock protein. Neural mechanisms are represented by a reduced release of noradrenaline from the sympathetic nerve endings and a reduced sensitivity of myocardium to noradrenaline. Finally, vascular endothelial cells take part in preconditioning by means of an increased production of nitric oxide which seems to exert a protection against arrhythmias.
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