Allopurinol improves endothelial dysfunction in chronic heart failure.
BACKGROUND
Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure.


RESULTS
We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy.


CONCLUSIONS
We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.
Farquharson
Colin A J
CA
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
Butler
Robert
R
Hill
Alexander
A
Belch
Jill J F
JJ
Struthers
Allan D
AD
D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase