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Am J Physiol Endocrinol Metab 294: E551-E557, 2008. First published December 18, 2007; doi:10.1152/ajpendo.00467.2007
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Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis

Xiao-jun Zhang,1,2 Oivind Irtun,1,2 David L. Chinkes,1,2 and Robert R. Wolfe1,2

1Metabolism Unit, Shriners Hospital for Children and 2Department of Surgery, The University of Texas Medical Branch, Galveston, Texas

Submitted 19 July 2007 ; accepted in final form 12 December 2007

The present experiment was designed to measure the synthetic and breakdown rates of muscle protein in the hindlimb of rabbits with or without clamping the femoral artery. L-[ring-13C6]phenylalanine was infused as a tracer for measurement of muscle protein kinetics by means of an arteriovenous model, tracer incorporation, and tracee release methods. The ultrasonic flowmeter, dye dilution, and microsphere methods were used to determine the flow rates in the femoral artery, in the leg, and in muscle capillary, respectively. The femoral artery flow accounted for 65% of leg flow. A 50% reduction in the femoral artery flow reduced leg flow by 28% and nutritive flow by 26%, which did not change protein synthetic or breakdown rate in leg muscle. Full clamp of the femoral artery reduced leg flow by 42% and nutritive flow by 59%, which decreased (P < 0.05) both the fractional synthetic rate from 0.19 ± 0.05 to 0.14 ± 0.03%/day and fractional breakdown rate from 0.28 ± 0.07 to 0.23 ± 0.09%/day of muscle protein. Neither the partial nor full clamp reduced (P = 0.27–0.39) the intracellular phenylalanine concentration or net protein balance in leg muscle. We conclude that the flow threshold to cause a fall of protein turnover rate in leg muscle was a reduction of 30–40% of the leg flow. The acute responses of muscle protein kinetics to the reductions in blood flow reflected the metabolic priorities to maintain muscle homeostasis. These findings cannot be extrapolated to more chronic conditions without experimental validation.

stable isotope; gas chromatograph-mass spectrometer; arteriovenous balance; fractional synthetic rate; fractional breakdown rate



Address for reprint requests and other correspondence: R. R. Wolfe, Dept. of Geriatrics, Center for Translational Research in Aging & Longevity, Univ. of Arkansas Medical School, 4301 Markham Slot 806, Little Rock, AR 72205 (e-mail: rwolfe2{at}uams.edu)







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