Leukocyte-derived metabolites of arachidonic acid in ischemia-induced myocardial injury.
Within minutes of occlusion of a major coronary artery the polymorphonuclear leukocytes (PMNs) are activated whereby they adhere to the vascular endothelium and migrate through the endothelial layer. Interactions with the endothelium can promote increased vascular resistance, diminished collateral flow, capillary blockade, and predisposition to vasospasm, as well as enhanced vascular permeability. On subsequent reperfusion entrapped leukocytes contribute to the no-reflow phenomenon, while more leukocytes gain access to the previously ischemic region. The leukocytes infiltrate the myocardium where they exacerbate the process of tissue injury and the development of arrhythmias. The release of leukocyte-derived mediators including arachidonic acid (AA) metabolites and oxygen-derived free radicals probably underlies these activities of the leukocytes. PMNs contain active lipoxygenase enzymes capable of metabolizing AA to products that are not normally found in the myocardium, and can dominate the metabolic profile of that tissue, leading to changes in myocardial integrity and function. Inhibitors of the lipoxygenase enzymes suppress the accumulation of leukocytes into the ischemic myocardium and reduce infarct size. However, because the drugs prevent cell invasion it cannot be inferred that a lipoxygenase metabolite per se is deleterious to the ischemic heart, inasmuch as any leukocyte-dependent mechanism of injury will be attenuated whether it is mediated by eicosanoids or by any other leukocyte-derived product. Additional studies with specific inhibitors/antagonists are required to determine the biochemical mechanisms underlying the different aspects of leukocyte-mediated myocardial injury.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism
D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid