Hepatomuscular failure in septic catabolism: altered muscular response to plasma proteolytic factor in decreased hepatic mitochondrial redox potential.
To estimate the contribution of muscle protein in whole-body protein catabolism, the muscular contribution index (MCI; urine 3-methylhistidine/urine total nitrogen) was determined in 49 cases of elective laparotomy, together with the arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential. MCI increased after operation and the occurrence of severe infection, provided KBR was maintained above 0.7. In patients with sepsis, however, MCI decreased dependently with KBR (n = 33; p less than 0.01). In these patients, plasma proteolysis-inducing activity determined by in vitro bioassay increased in inverse proportion to KBR (n = 20, p less than 0.01). Moreover, plasma concentrations of not only aromatic but also branched-chain amino acids markedly increased when KBR decreased to below 0.4 (n = 23; p less than 0.05). Thus the role of muscle protein in septic catabolism is diminished under reduced hepatic mitochondrial redox potential, despite the rapid increase of proteolysis-inducing activity. This finally leads to the failure of amino acid uptake by muscles, as well as liver. These results suggest that the deteriorated substrate exchange may form the metabolic background for multiple systems organ failure, which is often preceded by reduced KBR.
Kiuchi
T
T
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Yamaguchi
T
T
Takada
Y
Y
Konishi
Y
Y
Shimahara
Y
Y
Mori
K
K
Kobayashi
N
N
Yamaoka
Y
Y
Ozawa
K
K
D015415:Biomarkers / Q000097:blood / Q000652:urine; D002763:Cholecystectomy; D003082:Colectomy; D005260:Female; D005743:Gastrectomy; D006498:Hepatectomy; D006801:Humans; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008762:Methylhistidines / Q000652:urine; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D011183:Postoperative Complications / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*
D015415:Biomarkers; D007657:Ketone Bodies; D008762:Methylhistidines; D009124:Muscle Proteins; C028118:3-methylhistidine