Oxygen Free Radicals and the Effect of a Free Radical Scavenger in Patients with Intermittent Claudication

Abstract

Oxygen free radicals (OFRs) are implicated in tissue injury during postischemic reperfu sion and play an important role in the pathogenesis of atherosclerosis. In patients with intermittent claudication the ischemia-reperfusion phenomenon could be reproduced after exercise, thus influencing the evolution of chronic peripheral arterial occlusive disease (CPAOD). The aim of this study was to investigate the behavior of OFRs and the effect of a free radical scavenger in patients with stage II_B CPAOD. Malondialdehyde (MDA), a reliable index of OFRs production, was measured in the serum of 19 patients with stage II_B CPAOD and 42 healthy controls. The blood samples were collected from a foot vein in resting condition and during reperfusion after 5 minutes of provoked ischemia. These measurements were repeated after 3 and 12 weeks of oral treatment with the free radical scavenger trimetazidine hydrochloride (60 mg daily). Statistical analysis of the findings revealed that resting MDA was significantly higher in claudicants when compared to the healthy controls (1.247 ±0.25 μmol/L vs 1.021 ±0.278 μmol/L, p<0.005). During postischemic reperfusion (PIR) the MDA levels were significantly increased in claudicants (resting vs PIR: 1.247 ± 0.25 vs 4.60 ± 0.86 μmol/L, p<0.001). The administration of trimetazidine led to a significant reduction of the PIR MDA levels (before treatment 4.60 ±0.86 μmol/L vs 3 weeks 3.93 ±0.63 μmol/L and vs 12 weeks of treatment 2.98 ±0.29 μmol/L, p < 0.001 and p < 0.001, respectively). These findings indicate that claudicants are at increased risk of oxidative damage after exercise. Long- term administration of the free radical scavenger trimetazidine attenuates reperfusion injury in patients with stage II_B CPAOD.