Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion

Abstract

Objective: Ischemia-reperfusion (IR) injury causes tissue injury and endothelial dysfunction. There is evidence that oxidative stress plays an important role.

Methods: We tested if IR-induced endothelial dysfunction could be prevented by administration of the antioxidant vitamin C. Twenty-six healthy male subjects and eight male patients with peripheral arterial disease (PAD) were enrolled in this randomised placebo-controlled study. Forearm blood flow (FBF) measurements in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (NTG; endothelium-independent) were performed before and after forearm ischemia for 20 min. FBF responses were reassessed during reperfusion with intra-arterial co-administration of 24 mg/min vitamin C or placebo. In six volunteers responses to the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) were also assessed before and after ischemia with and without vitamin C.

Results: ACh-induced vasodilation was blunted in subjects receiving placebo after reperfusion (p<0.05 versus baseline). Administration of vitamin C completely prevented impaired responsiveness. NTG-induced vasodilation was not affected by reperfusion or vitamin C. This finding was consistent in patients with PAD and impaired endothelial function, where local vitamin C infusion restored FBF reactivity to ACh before and after IR injury (p<0.05 versus baseline). Again, NTG-induced vasodilation was not affected. Blunted L-NMMA responses seen during reperfusion could be completely reversed by vitamin C.

Conclusions: Our data indicate that IR-induced vascular injury can be prevented by administration of antioxidants.