MITOCHONDRIAL RESPIRATION AFTER SEPSIS AND PROLONGED HYPOXIA

Recently, marked oxygen dependence of respiration by isolated mitochon dria after exposure to prolonged hypoxia has been described. Because m itochondrial oxygen-dependent respiration could significantly influenc e oxygen consumption during critical illness; we sought to confirm the oxygen-dependent behavior of mitochondria. We hypothesized that mitoc hondria isolated during sepsis would exhibit increased oxygen dependen ce. We isolated rat liver mitochondria 16 h after cecal ligation and p uncture 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 wad stable over a 8 0-min period of hypoxia for control rats and decreased slightly for se ptic rats (10-15%). State 3 respiration was 10% lower when mitochondri a were reoxygenated at low (15-25 Torr) versus high (90-100 Torr) and low (10-15 Torr) versus intermediate (40-45 Torr) oxygen tension. Oxyg en consumption with ascorbate + N,N,N',N'-tetramethyl-p-phenylenediami ne was 20% lower at low versus high oxygen tension. Nb increase in oxy gen dependence was observed during 1 h of hypoxic incubation. Our data indicate only a modest oxygen dependence of respiration between 10 an d 100 Torr, which is similar for septic and control mitochondria. Addi tionally, oxygen dependence did not increase significantly during a I- h hypoxic exposure for well-coupled mitochondrial preparations.