The objective of this study was to investigate early effects of peritoneal
inflammation on the mitochondrial function in the vital organs, liver and kidney, and their relation to inflammatory and oxidative stress mediators. The study was performed on 14 domestic pigs. Peritoneal
inflammation was induced in anesthetized pigs after a midline
laparotomy by autologous feces. Fluid
resuscitation maintained a MAP above 60 mmHg. Animals were sacrificed 12 h later, and tissue samples were obtained to determine mitochondrial function,
mRNA levels of relevant genes [inducible
NO synthase (iNOS), inducible HO (HO-1),
tumor necrosis factor-alpha (
TNF-alpha)], generation of
reactive oxygen species (ROS), and HO-1 activity. We found impaired mitochondrial function in both liver and kidney, based on decreased state 3 respiration in the liver and increased states 2 and 4 respiration in the kidney at 12 h. This was accompanied by increased
TNF-alpha protein in the blood and up-regulation of
TNF-alpha mRNA in the liver. Free
iron was elevated in the liver but not in the kidney. In the kidney, mitochondrial ROS production was increased.
Nitric oxide levels in blood remained unchanged, corresponding to unchanged levels of iNOS
mRNA expression in liver and kidney. Similarly, HO-1
mRNA and
heme oxygenase (HO)-activity were unchanged. The inflammatory response in the absence of characteristic septic symptoms was not associated with morphological organ damage at this early time point. Peritoneal
inflammation in pigs caused
mitochondrial dysfunction in liver and kidney, preceding signs of organ damage. We did not find proof that
mitochondrial dysfunction was due to increased levels of either
nitric oxide (NO) or products of HO, but it was accompanied by increased levels of oxidative stress markers.