December 17, 2007

Amino Acid Supplementation, Blood Flow, and Leg Muscle Protein Synthesis in Peripheral Arterial Disease

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Lois A. Killewich, MD, PhD, Demidmaa Tuvdendorj, MD, PhD, Michael B. Silva, Jr., MD.
University of Texas Medical Branch, Galveston, TX, USA.

Background: Walking intolerance in peripheral arterial disease (PAD) is attributed to reduced blood flow, but muscle abnormalities (reduced protein synthesis) contribute. In healthy elderly, amino acid (AA) supplementation augments leg muscle protein synthesis, which over the long-term improves walking. However, augmentation is dependent upon delivery of AA to muscle via blood. Since PAD patients have reduced blood flow, delivery of AA to muscle could be restricted, preventing stimulation of protein synthesis. We investigated whether reduced leg blood flow in PAD patients would result in reduced basal and AA-stimulated protein synthesis compared to healthy elderly, and whether leg revascularization, by increasing blood flow, would increase synthesis.
Methods: Two groups participated: 11 claudicants and 9 age- and sex-matched healthy controls. Both groups underwent measurement of calf blood flow (strain gauge plethysmography) and protein synthesis (calf muscle biopsies) by measurement of fractional synthetic rate (FSR, %/hour) using stable isotopes. Gas chromatography-mass spectroscopy was used to measure incorporation. Following measurement of basal FSR, both groups drank 15g of essential amino acids, and the measurements of FSR were repeated. The PAD group then underwent surgical bypass to increase blood flow; protein synthesis measurements were repeated 4-6 weeks after.
Results: Calf blood flow was reduced in PAD pre-bypass compared to controls (1.44±0.46 vs. 2.42±0.53 ml/min/100mg tissue, p=.005). Leg revascularization increased blood flow (2.45±0.39, p=.009). Basal and AA-stimulated FSR in the PAD group pre-bypass were equivalent to controls (p>.05). Leg bypass produced further increases (p<.05) in FSR in the PAD patients (table).


	Control	PAD pre-bypass	PAD post-bypass
Basal FSR	0.065±0.026	0.060±0.041	0.111±0.101
AA-stimulated FSR	0.090±0.015	0.086±0.039	0.243±0.145

Conclusions: Reduced calf blood flow in PAD does not limit basal calf muscle protein synthesis nor its enhancement by amino acids. Normalization of blood flow with revascularization produces further increases. These findings suggest that long-term protein supplementation may provide a mechanism to increase walking in PAD.

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