ORGAN SPECIFIC RELATIONSHIP BETWEEN MITOCHONDRIAL FUNCTION AND TISSUE DAMAGE IN A MODEL OF PERITONITIS IN PIGS

Abstract

Introduction: The aim of this study was further clarification of the impact of mitochondria to multiple organ failure induced by septic shock. Methods: Peritonitis was induced in pigs by inoculating autologue feces pellets suspended in saline. Liver, heart, and kidney withdrawn 7 hours later were used for histological examination and determination of mitochondrial function. Since one of the mechanisms causing necrosis is a decreased energy supply within the cells, in tissue homogenates of the same organs we also determined the rate of mitochondrial respiration in state 3, which reflects the rate of ATP synthesis. Results: No morphological signs of damage were found in the kidney. In contrast, multiple focal necroses were observed in heart and liver. The state 3 respiration rates were significantly increased in kidney of pigs with peritonitis compared to controls with both substrate of complex I (glutamate-malate) and substrate of complex II (succinate). In contrast, the state 3 respiration rates in liver were significantly decreased both with succinate and with glutamate-malate. A similar decrease in state 3 respiration rates was observed in heart but only with substrate of complex I, indicating malfunction of mitochondria in heart is likely due to a defect in complex I. Conclusions: Our data show organ specific relationship between mitochondrial dysfunction and tissue damage. This supports an existing hypothesis that mitochondria are involved as mechanisms of peritonitis-induced tissue damage.