Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion.
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.
Pleiner
Johannes
J
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Schaller
Georg
G
Mittermayer
Friedrich
F
Marsik
Claudia
C
MacAllister
Raymond J
RJ
Kapiotis
Stylianos
S
Ziegler
Sophie
S
Ferlitsch
Arnulf
A
Wolzt
Michael
M
D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000975:Antioxidants; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001205:Ascorbic Acid