Chronic heart failure can be treated with a drug that is used to treat gout according to a scientist at the University of Dundee who publishes his findings this week in the American Heart Association journal.
Professor Allan Struthers has found that the drug - allopurinol improves blood vessel function in heart failure patients possibly by blocking the creation of harmful free radicals.
"These results are the first to show that treatment with alloprurinol can improve vessel dilation in heart failure patients," said Allan Struthers, professor of cardiovascular medicine and therapeutics at the University of Dundee. "The data are particularly noteworthy because allopurinol is sometimes prescribed anyway in heart failure patients, although only when gout co-exists. It is safe and relatively cheap."
This study belongs to the TICR group who are currently fundraising for a new institute at Ninewells, Dundee.
Chronic heart failure (HF) - when the heart cannot pump enough blood to meet the body's needs, is a common condition that causes death and disability. People with HF often experience chest pain and breathlessness when they are physically active. In people with HF, the vessels fail to relax, forcing the failing heart to work even harder. The diuretic drugs used to treat the fluid retention of heart failure can result in gout, a buildup of uric acid in the blood. Gout occurs when excess uric acid is converted to sodium urate crystal and deposits in joints and other tissues, often in the big toe. Hence, the need for allopurinol in those heart failure patients who do develop coincidental gout.
HF is also linked to oxidative stress, an increase in harmful free radicals that can damage blood vessels. The free radical superoxide is a form of oxygen that neutralizes nitric oxide, a substance created by the endothelium (the inner lining of the arteries) that dilates healthy vessels to accommodate increased demands during exercise.
In this randomized, placebo-controlled, double-blind crossover study, researchers gave 11 patients with mild to moderate HF allopurinol or placebo daily for one month. While measuring the response, the researchers then gave the subjects a short-acting drug called acetylcholine that acts on the endothelium to cause dilation in healthy vessels. Next, they crossed-over the patients to either allopurinol or placebo and repeated the experiment. They discovered that the allopurinol increased average forearm blood flow nearly 50 percent more than the placebo, says Struthers.
"Allopurinol is thought to work by blocking the action of xanthine oxidase, which produces the superoxide that promotes oxidative stress," he says. "Much of the previous work on reducing free radicals has focused on using antioxidant vitamins to negate their effect. This represents an alternate strategy of preventing the formation of oxygen-free radicals." It is also possible the drug reduces concentrations of uric acid, the culprit in gout. Earlier studies have shown an association between mortality and uric acid concentration, he says. Uric acid concentrations fell nearly 60 percent in patients taking allopurinol, even though their levels were in the normal range to begin with, he says. "We cannot tell from this study, whether allopurinol produced its benefit by way of decreasing superoxide anions or decreasing uric acid or both," he says.
Struthers says similar results have been found in patients with diabetes and high cholesterol levels, two other conditions associated with high levels of free radicals. In an accompanying editorial, Ulf Landmesser, M.D., and Helmut Drexler, M.D., professors at Medical School Hanover (Germany), praised the work saying, "If this concept holds true and can be confirmed in a larger patient population - it could pave the way to an inexpensive and possibly effective addition to the treatment of patients with chronic heart failure."
Perhaps allopurinol could improve the quality of life for patients with CHF by improving their exercise capacity, the ability to exert themselves without experiencing painful symptoms, a possibility outlined by Drexler in a 1998 Circulation article, Struthers says. Co-authors are Colin A. J. Farquharson, M.B.CH.B., M.R.C.P.(UK); Robert Butler, M.D., M.R.C.P. (UK); Alexander Hill, Ph.D.; and Jill J. F. Belch,M.D., F.R.C.P.
This research was funded by the British Heart Foundation.
See http://circ.ahajournals.org/cgi/content/abstract/106/2/221
Contact Professor Allan Struthers 01382 632574.