Pathogenesis of varicose veins and implications for clinical management.

Varicose veins (VVs) classically result from venous hypertension owing to incompetence of the major communications between the superficial and deep veins of the lower extremity. In a significant number of patients, there is no demonstrable truncal saphenous reflux and varicosities are the result of isolated perforating and nonsaphenous vein incompetence. The clinical and histologic features of VVs are the result of disruption of the normal architectural structure of the venous wall as a consequence of remodeling of the extracellular matrix (ECM) in response to increased venous distention and altered hemodynamic shear stress. Although a number of genes, growth factors, proteases, and their inhibitors known to modulate the ECM have been implicated in the pathogenesis of VVs, their etiology remains unknown. The complex variations in venous anatomy in patients with VVs require detailed vein mapping to determine the source and drainage locations of reflux if the rates of residual and recurrent varicosities are to be reduced. The distinct pathogenic mechanisms involved in the development of VVs have important implications for the management of VVs that include a wide spectrum of treatment modalities ranging from reassurance, alternative medicines, conservative management or compression therapy, and surgical or endovascular therapy.

Amino acids stimulate leg muscle protein synthesis in peripheral arterial disease.

OBJECTIVE: Older patients with peripheral arterial disease (PAD) and intermittent claudication have impaired walking ability resulting from reduced lower extremity blood flow. Evidence suggests that leg muscle abnormalities may also contribute to walking intolerance in claudicants. In healthy elderly people, leg muscle protein synthesis can be augmented by nutritional supplementation with amino acids; preliminary data suggest that this increases muscle mass, walking ability, and functional status. In this study, we investigated whether amino acid supplementation would improve leg muscle protein synthesis in elderly PAD subjects, given that reduced leg blood flow might restrict the availability of amino acids to muscle. METHODS: Two groups participated in the study: a group of 11 claudicants (mean age, 62 years; mean ankle-brachial index, 0.62; 46% male) and a group of 9 age- and sex-matched healthy controls (mean ankle-brachial index, 1.1). Both groups underwent measurement of leg blood flow by using strain gauge plethysmography, as well as measurement of baseline and amino acid-stimulated protein synthesis in leg muscle. Protein synthesis was quantified from calf muscle biopsy samples by measurement of the fractional synthetic rate (FSR) of protein, by using the incorporation of the stable isotope l-[ring-(2)H(5)]-phenylalanine into muscle protein. Total protein was extracted from muscle samples, and gas chromatography/mass spectroscopy methodology was used to measure incorporation rates. After measurement of basal FSR, all subjects were given an oral drink of 15 g of essential amino acids, and the measurements of FSR were repeated. Data are expressed as mean +/- SD; statistical analysis of differences between the two groups (with and without amino acid supplementation) was performed by using analysis of variance with repeated measures. RESULTS: Calf blood flow was reduced in the PAD subjects compared with controls (1.44 +/- 0.53 mL/min per 100 mg of tissue vs 2.40 +/- 0.57 mL/min per 100 mg of tissue; P = .005; t test). FSR in the basal state was equivalent between the two groups (healthy, 0.060% +/- 0.025% per hour; PAD, 0.061% +/- 0.029% per hour; P = .97). Equivalent increases (P < .05) occurred in both groups in response to oral amino acid supplementation (healthy, 0.087% +/- 0.012% per hour; PAD, 0.104% +/- 0.041% per hour; P > .05; analysis of variance). CONCLUSIONS: Despite reduced leg blood flow, elderly PAD patients synthesize calf muscle protein in the basal state in a fashion similar to that in healthy elderly people. More importantly, administration of exogenous amino acids produces a significant increase in protein synthesis in these patients that is also equivalent to that in healthy elderly people. Our goal is to use these results as the basis for an intervention study to determine whether long-term oral amino acids, by augmenting calf muscle protein synthesis, increase calf muscle mass, walking ability, and functional status in elderly claudicants.