This is a proposal to establish a Trauma Research Center at The University of Texas Medical School at Houston for the purpose of elucidating in animal models the antecedents to multiple organ failure. The investigators will test the hypothesis that splanchnic organ failure (liver, gallbladder, pancreas and gut) is a primary early event in the syndrome.
The specific aim encompass five interrelated major areas of inquiry. PROJECT I will examine the response of biliary and gut motility in response to hemorrhagic shock. Opossums will be chronically instrumented for assessment of gallbladder absorption, contractility and emptying, biliary sphincter and gut motility, enterohepatic circulation of bile acids, enterobacteriology, and portal translocation of enteric bacteria and endotoxin. PROJECT II will compare the rate of release of gastrointestinal peptides (insulin, glucagon, somatostatin, pancreatic polypeptide, gastrointestinal polypeptide, cholecystokinin, gastrin, secretin, and vasoactive polypeptide) to specific aspects of hepatic function (organic anion uptake, glucose metabolism, protein synthesis hormone receptor binding, and hepatic regeneration). These relationships will be studied in the pig in the normal state as well as following cardiogenic, hemorrhagic and endotoxic shock. PROJECT III will examine the effects of hypoxia, hemorrhagic shock and spesis on normal splanchnic eicosanoid production. These studies will then determine subsequent effects of altered eicosanoid biosynthesis on the splanchnic circulation, splanchnic visceral function and general systemic circulation. PROJECT IV will focus on the role of the intestinal barrier in preventing the translocation of enteric bacteria into the portal or systemic circulations. Oxygen-free radical activity will be compared to morphologic changes within the gut epithelium following hemorrhagic shock and modification by free radical scavengers.
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