PATHOGENESIS OF MULTIPLE ORGAN FAILURE

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.