The content and nature of dietary polyunsaturated fat can have important effects upon cell function and upon systems as diverse as the vasculature or those mediating immunity. Polyunsaturated lipids of the n-3 type and certain n-6 fatty acids may protect against, or alter the occurrence of, diseases such as coronary atherosclerosis and arthritis. Altered eicosanoid (prostaglandins and thromboxanes) formation may underlie these potentially beneficial effects. However, in addition to an action upon blood vessels and joints, preliminary data from this and other laboratories indicate that the dietary n-3 fatty acids can directly improve the course and outcome of septic shock. Such effects are particularly important as septic shock is not only difficult to treat and often afflicts young people, but in addition has a devastating mortality rate that may be as high as 50%. Even small improvements in management may have important effect on survival. Currently available nutrition products used to support such patients contain little n-3 fatty acids, but have substantial amounts of potentially harmful n-6 fats. Certain n-6 fats may not only fail to offer protection, but may have deleterious effects on vascular tone and tissue perfusion. Preliminary data suggests altered vascular responsiveness as the causative factor. Our purpose is to define in a porcine model the effects of n-3 fatty acids on the physiologic and eicosanoid response to sepsis. Specifically, these studies will determine: (1) whether platelets and endothelial cells release of eicosanoids is influenced by incubation with specific n-6 and n-3 fatty acids, and whether release of these eicosanoids is affected by extracellular fatty acids without the acids necessarily incorporated into the membrane phospholipids of these cells. (2) Whether these same dietary fatty acids influence release of eicosanoids from, and contractility of, pulmonary arteries in vitro. (3) Whether modification of dietary lipid affects platelet function after i.v. administration of low-dose endotoxin. (4) Whether addition of n-3 fatty acids or gamma-linolenic acid to the diet influences the in vitro interaction between platelets and arterial endothelium. To the extent that the pathophysiologic and eicosanoid response to sepsis is altered, these experiments will clarify the role of dietary 18 and 20 carbon chain fatty acids in the pulmonary vascular response to a stress such as sepsis.

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Mayo Clinic, Rochester
United States
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Murray, M J; Svingen, B A; Yaksh, T L et al. (1993) Effects of endotoxin on pigs prefed omega-3 vs. omega-6 fatty acid-enriched diets. Am J Physiol 265:E920-7