In vivo 31P nuclear magnetic resonance spectroscopy of skeletal muscle energetics in endotoxemic rats: a prospective, randomized study.

Objective: To identify possible alterations in the skeletal muscle high-energy phosphate metabolism at the early phase of endotoxic shock in rats.
Design: A prospective, randomized study of skeletal muscle energetics in endotoxemic and in control rats, by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy at rest, under regional ischemia, and during reperfusion.
Setting: Biochemical NMR laboratory equipped for surgery and hemodynamic monitoring.
Subjects: Wistar rats were randomized to different groups. Eight rats were injected with Escherichia coli endotoxin (15 mg/kg, survival time 19 +/- 4 hrs) intraperitoneally. Seven other rats served as controls. The additional nine rats were studied for the saturation recovery pulse sequence.
Interventions: In the treatment group, endotoxin was injected 8 hrs before NMR spectroscopy. The right hind limbs were studied under anaesthesia using a surface coil NMR probe. Their high-energy phosphate contents and intracellular pH were determined by 31P NMR spectroscopy. After baseline measurements, an ischemia-reperfusion challenge was imposed on the muscle by transient clamping of the abdominal aorta. Contralateral femoral artery pressure was constantly monitored.
Measurements and Main Results: During the baseline period, the endotoxin-treated muscles did not show any difference in the distribution of the high-energy phosphate compounds or in intracellular pH, as compared with the controls. Ischemia resulted in a significantly faster decline of the inorganic phosphate/creatine phosphate ratio in the endotoxin-treated rats (1.35 +/- 0.17 vs. 0.51 +/- 0.06 at the end of the 38-min ischemic period). Skeletal muscle acidosis developed earlier and was deeper in the endotoxemic animals (pH: 6.94 +/- 0.02 vs. 7.02 +/- 0.03 at the end of ischemia). During reperfusion, the calculated time constants of recovery of inorganic phosphate to phosphocreatine ratios were identical between groups.
Conclusions: Resting nonischemic muscles of endotoxin-treated rats show no evidence of alterations in high-energy phosphate metabolism. However, under ischemic conditions, high-energy phosphate metabolism deteriorates faster in the skeletal muscles of treated animals. These data support the hypothesis of a greater mismatch during perfusion at very low pressure between residual oxygen availability and oxygen needs in the endotoxin-treated muscle cell.