Alterations of hepatic mitochondrial function in a model of peritonitis in immature rats.
Severe intra-abdominal infection results in significant metabolic dysfunction, multiple systems failure, and mortality. Although the course of peritonitis is particularly rapid and severe in neonates and small children, its physiologic consequences have been poorly studied in these age groups. In order to assess hepatic mitochondrial integrity in a model of fulminant peritonitis in immature animals, the following study was undertaken. Thirty-three immature Sprague-Dawley rats (21 to 28 days of age) and 32 mature rats (weight greater than 250 g) were anesthetized and laparotomies performed. The animals received either cecal ligation and gross perforation (CLP) or cecal manipulation alone (sham). Animals were killed at 2 and 4 hours and livers removed. Mitochondria were isolated by differential centrifugation. Mitochondrial respirations were studied polarographically with glutamate and succinate as substrates in the presence (state 3) and absence (state 4) of adenosine diphosphate (ADP). The Respiratory Control Index (RCI) is the ratio of state 3 to state 4 respiration and is a sensitive indicator of mitochondrial coupling. Results revealed that in mature animals, peritonitis produced a significant increase in RCI with glutamate as substrate (5.2 +/- 0.2) by 4 hours duration as compared with sham operated rats (4.3 +/- 0.1, P less than 0.01). Succinate as substrate revealed no significant alteration in mitochondrial coupling in mature rat hepatic mitochondria in animals subjected to peritonitis. By contrast, peritonitis in immature animals produced a significantly decreased RCI (3.6 +/- 0.2) with glutamate as substrate as compared with sham operated animals (4.8 +/- 0.2, P less than 0.01) by two hours duration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D005971:Glutamates / Q000378:metabolism; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption; D010538:Peritonitis / Q000378:metabolism*; D011048:Polarography; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005971:Glutamates