THE DURATION OF INFECTION MODIFIES MITOCHONDRIAL OXIDATIVE CAPACITY IN RAT SKELETAL-MUSCLE

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr store s in skeletal muscle. To determine if systemic infection impairs mitoc hondrial function, in vivo P-13 magnetic resonance spectroscopy (P-31 MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sh am operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physi ologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. Hig h resolution (8.45 Tesla) P-31 MRS spectra, obtained at rest and durin g exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP , PCr/P-i ratios, and intracellular pH. Steady-state muscle exercise w as induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 m in. Recovery of PCr/(PCr + P-i) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate th e half time for PCr recovery, the initial PCr resynthesis rate, and th e maximal oxidative ATP synthesis rate, which reflect the rephosphoryl ation of ADP and are therefore measures of mitochondrial oxidative cap acity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P-i ratios decreased incrementally (7% in 24 de grees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after o peration the half time for PCr recovery was shortened while the initia l PCr resynthesis rate and maximal oxidative ATP synthesis rate were a ccelerated in CLP animals compared to controls. By 48 hr these indices of mitochondrial function were significantly slowed. Intracellular pH was well maintained in resting skeletal muscle in all animals. These data demonstrate that the reduction in high energy phosphate (PCr) sto res observed during early sepsis are not secondary to mitochondrial dy sfunction; in fact, the organelles' ability to rephosphorylate ADP is enhanced. (C) 1995 Academic Press, Inc.