Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis

Abstract

Zhang X-j, Irtun O, Chinkes DL, Wolfe RR. Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis. Am J Physiol Endocrinol Metab 294: E551-E557, 2008. First published December 18, 2007 doi:10.1152/ajpendo.00467.2007.-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-13 C6]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 Ͻ 0.05) both the fractional synthetic rate from 0.19 Ϯ 0.05 to 0.14 Ϯ 0.03%/day and fractional breakdown rate from 0.28 Ϯ 0.07 to 0.23 Ϯ 0.09%/day of muscle protein. Neither the partial nor full clamp reduced (P ϭ 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 PROTEIN KINETICS in the skeletal muscle have been studied intensively under various conditions, including fasting, spaceflight, exercise, and catabolic illness (5,8,18). The importance of muscle protein metabolism is not only because of its contractile function but also because muscle is the largest mobilizable source of protein. Muscle catabolism provides free amino acids under catabolic states, thereby supporting the continual synthesis of essential proteins in other parts of the body (9,10,19,21). The synthesis of muscle protein, as well as breakdown, depends on blood flow, since the metabolic precursors and products have to be transported into, and removed from, the muscle through the blood stream.The muscle is proposed to have two vascular flow routes: nutritive and nonnutritive (4). Nutritive flow is able to exchange nutrients and hormones with the skeletal muscle myocytes. Although the nonnutritive flow does not have direct nutritional function, it carries a flow reserve and redistributes to nutrition routes in response to increased metabolic demand. It has been demonstrated that increased rates of m...

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