Mitochondrial respiration after sepsis and prolonged hypoxia.
Recently, marked oxygen dependence of respiration by isolated mitochondria after exposure to prolonged hypoxia has been described. Because mitochondrial oxygen-dependent respiration could significantly influence oxygen consumption during critical illness, we sought to confirm the oxygen-dependent behavior of mitochondria. We hypothesized that mitochondria isolated during sepsis would exhibit increased oxygen dependence. We isolated rat liver mitochondria 16 h after cecal ligation and puncture and found a 30-40% greater oxygen uptake compared with control rats under state 3 conditions. Mitochondria incubated in deoxygenated buffer were studied for oxygen dependence at 10-min intervals for 90 min. Mitochondrial respiration after reoxygenation was stable over a 60-min period of hypoxia for control rats and decreased slightly for septic rats (10-15%). State 3 respiration was 10% lower when mitochondria were reoxygenated at low (15-25 Torr) versus high (90-100 Torr) and low (10-15 Torr) versus intermediate (40-45 Torr) oxygen tension. Oxygen consumption with ascorbate+N, N, N', N'-tetramethyl-p-phenylenediamine was 20% lower at low versus high oxygen tension. No increase in oxygen dependence was observed during 1 h of hypoxic incubation. Our data indicate only a modest oxygen dependence of respiration between 10 and 100 Torr, which is similar for septic and control mitochondria. Additionally, oxygen dependence did not increase significantly during a 1-h hypoxic exposure for well-coupled mitochondrial preparations.
Taylor
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DE
Department of Medicine, University of Texas-Houston Medical Center, Houston, Texas 77030, USA.
Kantrow
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SP
Piantadosi
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CA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002432:Cecum; D000860:Hypoxia; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018805:Sepsis / Q000378:metabolism*; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D013997:Time Factors
D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid