Significance of myocardial eicosanoid production.
The precise role of eicosanoids in the development of myocardial injury during ischemia and reperfusion is still a matter of debate. Enhanced local production of these bioactive compounds appears to be a common response to tissue injury. Most likely, the cardiac tissue has the capacity to generate prostaglandins, thromboxanes as well as leukotrienes. Prostacyclin (PGI2) is the major eicosanoid produced by the jeopardized myocardium. In addition, at sites of tissue injury activation of platelets and infiltrating leukocytes results in the formation of considerable amounts of thromboxanes and leukotrienes. The production of eicosanoids requires prior release of arachidonic acid (AA) from phospholipids. Both ischemia and reperfusion are associated with a rise in the tissue level of AA. The absence of a proportional relationship between the tissue level of AA and the amounts of PGI2 produced suggests that the sites of AA accumulation and PGI2 formation are different. It is conceivable that AA accumulation is mainly confined to myocytes, whereas the capacity to synthesize PGI2 mainly resides in vascular cells. Both beneficial and detrimental effects of eicosanoids on cardiac tissue have been described. Prostaglandins act as vasodilators. Besides, some of the prostaglandins, especially PGI2, are thought to possess cyto-protective properties. Thromboxanes and leukotrienes may impede blood supply by increasing smooth muscle tone. Besides, leukotrienes augment vascular permeability. Experimental studies, designed to evaluate the effect of pharmacological agents, like PGI2-analogues and lipoxygenase and cyclo-oxygenase inhibitors, indicate that eicosanoids influence the outcome of myocardial injury.(ABSTRACT TRUNCATED AT 250 WORDS)
van Bilsen
M
M
Department of Physiology, University of Limburg, Maastricht, the Netherlands.
Engels
W
W
van der Vusse
G J
GJ
Reneman
R S
RS
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D015289:Leukotrienes / Q000502:physiology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology; D013931:Thromboxanes / Q000502:physiology
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes