Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: A randomized, double-blind, placebo-controlled trial

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 11 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 +/- 0.2 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 PFVVD and shows an improvement of macrocirculatory and microcirculatory parameters.