Oxygen extraction and vascular dilation are dependently increased in skeletal muscle during canine endotoxemia

The principal aim of these experiments was to evaluate the ability of a skeletal muscle to extract oxygen during endotoxemia, and determine if the decompensatory decrease in skeletal muscle vascular resistance that occurs after exposure to endotoxin is related to muscle oxygen uptake (VO2). A vascularly isolated denervated canine gracilis muscle was perfused in situ at a constant flow (5-7 mL/min/100 g). Endotoxemia was induced by a 30-min intravenous infusion of Escherichia coli endotoxin (2 mg/kg). Perfusion pressure and arteriovenous oxygen difference (a-v O2) were continuously measured, and muscle O2 extraction was calculated (VO2 = flow x a-v O2). These studies found that gracilis muscle oxygen uptake increased from a resting value of 0.30 mL O2/min/100 g to 0.63 mL O2/min/100 g (111% increase) by 90 min post-endotoxin. The arterial conductance (i.e., arterial dilation) increased 58% during this time. The amount of oxygen the muscle extracts was found to be directly related to the degree of vasodilation (r = .97), and inversely correlated to mean arterial pressure (r = .97). Pre-dilating the muscle with sodium nitroprusside did not alter oxygen extraction. However, after the introduction of endotoxin, a pre-dilated muscle increased VO2 94% by 90 min. These observations support the concept that endotoxin causes an increase in VO2 without producing a defect in the ability of muscle to extract oxygen. The vasodilation typically observed in skeletal muscle during endotoxemia is not the cause of the increased oxygen uptake. It seems likely that mediators released by endotoxin metabolically stimulate skeletal muscle cells, which increases oxygen demand, thus promoting vasodilation.