Objective
To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic
parameters in patients with peripheral artery disease.
Patients and Methods
Forty patients with Fontaine stage II peripheral artery disease who were seen between
September 2000 and March 2001 at the vascular laboratory and ward of the Division
of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind,
placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment
with intravenous glutathione twice a day or saline solution twice a day for 5 days.
Treatments were administered in a double-blind manner. The 2 groups of patients underwent
measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with
postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements
and tests were repeated 12 hours after the last infusion.
Results
Between the 2 groups, hemodynamic tests showed no differences in baseline values and
at rest after treatment. At rest, no differences were observed between basal and posttreatment
values; findings in the saline group were similar during tests before and after the
infusion period. In the glutathione group, we observed increases in PFWD (196±15 vs
143±11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end
of treatment (9.3±2 vs 2.8±0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion
units (PU), at the end of infusions (14.4±3.2 vs 6.18±1.5 PU; P<.005), with a greater area under the curve after treatment (705±103 vs 508±45 PU/s;
P<.001) and reduced time to flow motion (32±4 vs 48±11 seconds; P<.05).
Conclusion
In patients with peripheral artery disease, glutathione prolongs PFWD and shows an
improvement of macrocirculatory and microcirculatory parameters.
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REFERENCES
- Vitamin C intake and mortality among a sample of the United States population.Epidemiology. 1992; 3: 194-202
- Randomised controlled trial of vitamin E in patients with coronary artery disease: Cambridge Heart Antioxidant Study.Lancet. 1996; 347: 781-786
- Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease.Circulation. 1999; 99: 3234-3240
- Long-time treatment of intermittent claudication with vitamin E.Am J Clin Nutr. 1974; 27: 1179-1181
- Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension.Circulation. 1993; 87: 1468-1474
- Close relation of endothelial function in the human coronary and peripheral circulations.J Am Coll Cardiol. 1995; 26: 1235-1241
- The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress.N Engl J Med. 1991; 325: 1551-1556
- Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor.Nature. 1986; 320: 454-456
- Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.J Biol Chem. 1995; 270: 319-324
- Enhancement of platelet function by superoxide anion.J Clin Invest. 1977; 59: 959-965
- UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species.Br J Haematol. 1993; 83: 253-258
- Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells.J Arterioscler Thromb Vasc Biol. 1997; 17: 3570-3577
- Laminar shear stress and redox sensitive regulation of human vascular endothelial cell VCAM-1 gene expression [abstract].Circulation. 1994; 90 (Abstract 0438.): I-83
- Vascular free radical release: ex vivo and in vivo evidence for a flow-dependent endothelial mechanism.Circ Res. 1994; 74: 700-709
- Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression.J Cell Physiol. 1998; 175: 156-162
- The cardiovascular effects and implications of peroxynitrite.Cardiovasc Res. 1999; 44: 47-59
- Glutathione-ascorbic acid antioxidant system in animals.J Biol Chem. 1994; 269: 9397-9400
- Nitric oxide synthesis is impaired in glutathione-depleted human umbilical vein endothelial cells.Am J Physiol. 1993; 265: C728-C732
- Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents.J Am Coll Cardiol. 1993; 22: 854-858
- Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.N Engl J Med. 1986; 315: 1046-1051
- L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease.J Clin Invest. 1998; 101: 1408-1414
- Glutathione peroxidase potentiates the inhibition of platelet function by S-nitro-sothiols.J Clin Invest. 1995; 96: 394-400
- Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation.Circulation. 1998; 97: 2299-2301
- Metabolic activity of skeletal muscle in patients with peripheral arterial insufficiency.Eur J Clin Invest. 1974; 4: 9-15
- L-propionyl carnitine effect on postexercise and postischemic hyperemia in patients affected by peripheral vascular disease.Angiology. 1995; 46: 705-713
- Evaluation of compensation of chronic arterial occlusions [in German].Vasa. 1973; 2: 4-11
- Management of peripheral arterial disease (PAD).Int Angiol. 2000; 19: 73
Kappert A. Angiologia, fisiopatologia e clinica. In: Lehrbuch und Atlas der Angiologie. 12th ed (Italian edition). 1991: 77-78.
- Evaluation of postischemic hyperemia on the skin using laser Doppler velocimetry: study on patient s with claudication intermittens.Microvasc Res. 1986; 32: 289-299
- Laser Doppler flowmetry in evaluation of skin post-ischaemic reactive hyperaemia: a study in healthy volunteers and atherosclerotic patients.J Cardiovasc Surg (Torino). 1989; 30: 70-75
- Analysis of flow motion by the laser Doppler technique in patients with peripheral arterial occlusive disease.Int J Microcirc Clin Exp. 1988; 7: 223-236
- Guidelines for therapeutic studies on peripheral arterial occlusive disease in Fontaine stages II-IV [in German] [published correction appears in Vasa. 1993;22:190].Vasa. 1992; 21: 333-343
- Contributions of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery.Am J Physiol. 1997; 273: H2388-H2395
- Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability.J Am Coll Cardiol. 1999; 34: 507-514
- Periodic cutaneous blood flow during postocclusive reactive hyperemia.Am J Physiol. 1986; 250: H765-H768
- Microvascular vasomotion: origin of laser Doppler flux motion.Int J Microcirc Clin Exp. 1994; 14: 151-158
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© 2002 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
