HP19P EARLY ORGAN SPECIFIC MITOCHONDRIAL DYSFUNCTION SEEN DURING EXPERIMENTAL ACUTE PANCREATITIS

Background and Aims:   Multiple organ dysfunction syndrome (MODS) is the main cause of death in severe acute pancreatitis. Primary mitochondrial dysfunction is now thought to play a central role in the development and progression of organ failure in critical illness. The aim of this study was to investigate mitochondrial function in seven tissues during early acute pancreatitis in two experimental rodent models. Methods:   Twenty-eight male Wistar rats were studied. Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein induced acute pancreatitis; Group 3, (n = 7) sham surgical controls; Group 4 (n = 7), taurocholate induced acute pancreatitis. Animals were euthanased at 6 h from the start of the experimental protocol and mitochondrial function was assessed in the heart, lung, liver, kidney, pancreas, duodenum and jejunum. Mitochondrial function was assed using a substrate and inhibitor protocol on the Oroboros machine. Results:   Significant mitochondrial dysfunction was present in the pancreas, lung and jejunum in the models of acute pancreatitis compared to control groups. The heart, liver, kidney and duodenal mitochondria were unaffected. Conclusion:   This study found an early inhibition of mitochondrial function present selectively in the lung and jejunum during acute pancreatitis. Subsequent failure of these two organ systems is implicated in the morbidity and mortality associated with severe acute pancreatitis and MODS. These findings suggest that early mitochondrial dysfunction occurs selectively in certain organs remote from the pancreas as a key event during early pancreatitis. Further research is now needed to evaluate the use of early mitochondrial specific therapies in early acute pancreatitis.