Hepatic cellular hypoxia in murine peritonitis.
Reduced oxygen consumption and lactic acidosis were observed frequently in patients with peritonitis. This study was designed to evaluate whether reduced oxygen consumption is secondary to deficient oxygen delivery or is a function of primary injury to mitochondria. Peritonitis was produced in rats by cecal ligation and perforation. Animals were killed at 2, 4, and 6 hours and agonally. Oxygen 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 electron microscopy. Systemic blood pressure and oxygenation were monitored. Hepatic tissue oxygenation was examined using a surface oxygen electrode. Peritonitis resulted in acceleration of state 3 respiratory rates and increased respiratory control indices at all time intervals. Maximal respiratory control was observed at 4 hours with all substrates. Whole tissue mitochondria demonstrated mild swelling and thinning of membranes and matrix. Experimental and control isolates showed similar orthodox-to-condensed conformational changes. Hepatic tissue oxygenation declined to less than 10% of control by 6 hours, while arterial Po2 was unchanged. The conclusions of this study are that lethal peritonitis results in (1) no primary injury to the hepatic mitochondria, (2) increased efficiency of hepatic mitochondrial oxygen utilization, and (3) reduced hepatic tissue oxygenation. The exact mechanisms of defective oxygen delivery require further study.
D000818:Animals; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010538:Peritonitis / Q000150:complications* / Q000503:physiopathology; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013386:Succinates / Q000378:metabolism
D005971:Glutamates; D011773:Pyruvates; D013386:Succinates; D010100:Oxygen