HEPATIC CELLULAR HYPOXIA IN MURINE PERITONITIS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 85  (6) , 652-661
Abstract
Reduced O2 consumption and lactic acidosis are observed frequently in patients with peritonitis. Whether reduced O2 consumption is secondary to deficient O2 delivery or is a function of primary injury to mitochondria was studied. Peritonitis was produced in rats by cecal ligation and perforation. Animals were killed at 2, 4 and 6 h and agonally. O2 utilization was studied polarographically in isolated hepatic mitochondria with glutamate, pyruvate and succinate substrates. State 3, state 4, respiratory control index (RCI) and ADP:O ratios were determined. Whole tissue and isolated mitochondrial ultrastructure were examined by EM. Systemic blood pressure and oxygenation were monitored. Hepatic tissue oxygenation was examined using a surface O2 electrode. Peritonitis resulted in acceleration of state 3 respiratory rates and increased respiratory control indices at all time intervals. Maimal respiratory control was observed at 4 h with all substrates. Whole tissue mitochondria demonstrated mild swelling and thinning of membranes and matrix. Eperimental and control isolates showed similar orthodox-to-condensed conformational changes. Hepatic tissue oxygenation declined to less than 10% of control by 6 h, while arterial PO2 was unchanged. Lethal peritonitis results in no primary injury to the hepatic mitochondria, increased efficiency of hepatic mitochondrial O2 utilization and reduced hepatic tissue oxygenation. The exact mechanisms of defective O2 delivery require further study. [Defective O2 metabolism and lactic acidosis are predictors of death in severe sepsis].