The syndrome of Multiple Organ Failure (MOF) has profound effects on splanchnic visceral function and these effects are at least in part due to alterations in normal splanchnic circulation. Eicosanoids (prostaglandins and leukotrienes) have been implicated in normal and abnormal physiology of the splanchnic circulation. This proposal will examine the general hypothesis that hypoxia and hemorrhagic shock alter splanchnic eicosanoid production which has subsequent profound effects on the splanchnic circulation. splanchnic visceral function and the general systemic circulation. This general hypothesis encompasses a specific hypothesis that initial stage of shock causes release of splanchnic thromboxane A2 which decreases splanchnic perfusion and contributes to splanchnic hypoxia. Prostacyclin is generated in the muscularis of the bowel as a later secondary compensation which decreases intestinal vascular resistance but also decreases bowel smooth muscle motility contributing to ileus. The result of early tissue hypoxia and later ileus contributes to evolution of enteric sepsis with release of endotoxin, a potent agonist for systemic release of potent prostaglandins and leukotrienes. This proposal will identify the levels and source of enhanced eicosanoid biosynthetic activity found in the splanchnic circulation in hypoxia and shock. The data will provide insight to the levels in the cascade of arachidonic acid metabolism amenable to use in those patients exposed to conditions predisposing to the syndrome of MOF to avoid the long term sequelae of alterations in gastrointestinal tract function.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
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