Microcirculatory Changes of the Pancreas in Sepsis and the Relation to Exocrine Pancreatic Function in Rats

Charlotte Bühler Fellowship H 152 Sepsis and pankreas: exokrine secretionand microcirkulation Barabara TRIBL 08.05.2000 Microcirculatory changes of the pancreas in seosis and the relation to exocrine pancreatic function in rats 1. Clinic of Internal Medicine IV, Department of Gastroenterology and Hepatology, University of Vienna, 2. Critical Care Trauma Center, London. Ontario, Canada Sepsis my lead to progressive failure of multiple interdependent organs such as the lung, the kidney, the liver, the cardiovascular and the central nervous system. The function of the exocrine pancreas in sepsis is unknown. Histologic and ultrastructural changes of the pancreas in a hyperdynamic model of sepsis have been shown to be exaggerated over those noted in myocardium, striated muscle, liver and gut. Animal studies have shown an imoaired bicarbonate secretion in endotoxic an hypovolemic shock. In the first study in man we have recently demonstrated a significant impairment of pancreatic secretion of bicarbonate, amylase, trypsin and chymotrypsin in critically ill patients with septic shock. Since animal studies have demonstrated a depression of pancreatic blood flow it may be possible that pancreatic dysfunction complicating sepsis is a consequence of microcirculatory dysfunction in this syndrome. Since thorough investigation of microcirculatory alternations of the pancreas under septic conditions is not possible in man, further investigation in an animal model of sepsis is necessary. The objective of this research project is to correlate data of secretory studies of the exocrine pancreas with data of the microcirculation as well as data of cell injury of the pancreas in a normotensive model of sepsis which is induced by bacterial pneumonia in rats. This model of sepsis with a distant focus of infection has the advantage that direct inflammatory injury cannot complicate microcirculatory alternations of the pancreas as it may occur in peritonitis following cecum ligation and perforation. Examination of the exocrine pancreas is done by collection of pancreatic juice during stimulation of the exocrine pancreas by intravenous administration of secretin. Microcirculatory changes of the pancreas during normotensive sepsis in the same rat model is studied during early and late sepsis by using intravital microscopy. Data on cell injury will be obtained by application of the fluorescent dye propidium isodide, which allows identification of severly injured cells. If a microcirculatory impairment of the exocrine pancreas in this normotensive model of sepsis can be demonstrated, this would provide a strong rationale for application of therapeutical regimen that improve the splanchnic microcirculation in patients with sepsis and septic shock.