Sepsis does not impair tricarboxylic acid cycle in the heart.
Sepsis has been reported to cause mitochondrial dysfunction and inhibition of key enzymes that regulate the tricarboxylic acid (TCA) cycle. We investigated the effect of sepsis on high-energy phosphates, glycolytic and TCA cycle intermediates, and specific amino acids that are involved in regulating the size of the TCA cycle pool during changes in metabolic state of the heart. Sepsis was induced in 12 female rats by the cecal ligation and perforation technique under halothane anesthesia; seven control rats underwent cecal manipulation without ligation. At 36-42 h postsurgery, the rats were reanesthetized, the chest was opened, and the hearts were freeze-clamped. Perchloric acid extracts of the hearts were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy. There were no significant differences in the levels of the TCA cycle intermediates or high-energy phosphates between the septic and control rats. The major metabolic changes were the 28% decrease in alanine and the 31% decrease in glutamate in the septic hearts compared with control (P less than 0.05 and P less than 0.005, respectively). Phosphocholine, a component of membrane phospholipids, was increased by 91% in the septic hearts (P less than 0.01). We conclude that sepsis does not impair the TCA cycle or induce significant cellular ischemia in the heart. The increase in phosphocholine may represent significant cellular membrane disruption during sepsis.
Hotchkiss
R S
RS
Department of Anesthesiology, Washington University School of Medicine, St. Louis 63110.
Song
S K
SK
Neil
J J
JJ
Chen
R D
RD
Manchester
J K
JK
Karl
I E
IE
Lowry
O H
OH
Ackerman
J J
JJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002952:Citric Acid Cycle; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate; D006400:Hematocrit; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology
D010725:Phosphocreatine; D009243:NAD; D010758:Phosphorus; D009249:NADP; D000255:Adenosine Triphosphate