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Paolo Gresele, Rino Migliacci, Alessandra Procacci, Paola De Monte, Erminio Bonizzoni
Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication
Keywords: Flow-mediated vasodilation, intermittent claudication, ischemia/ reperfusion injury, nitric oxide
Ischemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day 1 (pre-treatment: aspirin = 3.1 0.5%, nitroaspirin = 3.9 0.7%, p = NS), and on day 28 (aspirin = 3.4 0.7%, NCX 4016 = 3.2 0.6%, p = NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = 1.15%, nitroaspirin = 1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirintreated group (1.46%) while it was abolished in the NCX 4016-treated group (+0.79%, p = 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-1 which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 97, 03/2007
Pages: 444 - 450