Escherichia coli endotoxin reduces cytochrome aa3 redox status in pig skeletal muscle

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Abstract
Objective To assess the effect of endotoxin on cytochrome aa3 (C aa3) redox status in a controlled blood flow preparation of pig isolated hindlimb, at a constant oxygen delivery (˙Do2limb) (constant flow period) and during progressive ischemia (decreasing flow period). Design Randomized, controlled experimental study. Setting University hospital experimental laboratory. Subjects Ten piglets. Interventions Hindlimb blood flow was restricted to the femoral vessels. The arterial femoral blood flow coming from the carotid artery was controlled by a roller occlusive pump. The femoral venous blood flow was returned to the jugular vein. During the first 100 mins, the hindlimb blood flow was maintained at a normal level and then decreased stepwise. Animals were randomized to receive 150 μg/kg endotoxin lipopolysaccharide (LPS; n = 5) or saline (control; n = 5). Measurements and Main Results Hindlimb muscle C aa3 redox status was monitored by near-infrared spectroscopy. Hindlimb ˙Do2limb and oxygen consumption (V̇o2limb) were calculated. In the LPS group, a rapid reduction of C aa3 redox status was observed after LPS administration, whereas the hindlimb blood flow remained normal with no change in ˙Do2limb and V̇o2limb. A progressive simultaneous decrease in ˙Do2limb and V̇o2limb was observed during the decreasing flow period with no further reduction in C aa3 redox status. In the control group, no change was observed in C aa3, ˙Do2limb, or V̇o2limb during the constant flow period. During the decreasing flow period, C aa3 redox status was reduced as ˙Do2limb and V̇o2limb decreased. Conclusion Our results suggest that endotoxin may induce a reduction of C aa3 redox status independently of ˙Do2 and V̇o2.