VCU news

By Lorraine Cichowski and Rakesh Kukreja

RICHMOND, Va. – A researcher at Virginia Commonwealth University has invented a new and potentially important use for the male impotence drug, Viagra – heart protection.

The discovery by Dr. Rakesh C. Kukreja, professor of internal medicine and Eric Lipman Chair in cardiology at VCU’s School of Medicine, is reported in the September issue of the American Journal of Physiology – Heart and Circulatory Physiology. The journal, published by the American Physiology Society, is available online at http://ajpheart.physiology.org/.

“Some people who are using Viagra may get an unintentional benefit of protecting the heart,” said Dr. Kukreja.  “If they develop a heart problem later, it might not be as bad.  These results are very exciting because of the possibility that one day we may be able to use Viagra for other cardiovascular diseases, in addition to erectile dysfunction in men.”

Kukreja’s discovery is particularly noteworthy because Viagra generally is not recommended or prescribed now to men with many types of heart problems.

Pfizer Inc. won Federal Drug Administration approval in March 1998 to manufacture and sell the drug, sildenafil, as an oral treatment for impotence, which affects millions of men.  In the past four years, Pfizer Inc. has sold enough of the drug, trade named Viagra, to fill 100 million prescriptions for 20 million patients worldwide, making Viagra one of the world’s largest-selling medicines.

Other than for treating impotence, however, little has been known about additional beneficial effects of Viagra, although researchers and clinicians worldwide have been seeking more uses for the medicine.  Shortly after it was released, reports linked Viagra to sudden heart attacks and hypotension during sex in men who were taking nitroglycerin for cardiovascular disease, prompting the FDA and Pfizer to amend prescription labels to warn doctors against prescribing the drug for impotence in patients with known heart conditions.

Kukreja began looking at Viagra early this year as part of his on-going research into “preconditioning,” which is a way to protect the heart muscle from serious damage in the future by subjecting it to very brief periods of deprivation of blood flow and, therefore, oxygen.  Kukreja and his colleagues at VCU’s School of Medicine have been studying preconditioning for 14 years.

Some preconditioning occurs naturally.  For example, research has shown that people who suffer angina (chest pain) before a heart attack tend to have fewer complications and deaths resulting from the heart attack than those who never suffered angina before the heart attack. At times preconditioning is planned by doctors for its therapeutic effects.  For example, drugs with preconditioning effects can be given to people with heart disease at risk of having a heart attack. Donor hearts removed for transplants and hearts undergoing surgery and placed on cardiopulmonary bypass also can benefit from preconditioning to protect the heart muscle from injury. (For more information, see http://www.americanheart.org/.)

“My hypothesis was that because Viagra causes dilatation of blood vessels and reduces blood pressure, that such a hypotensive effect might lead to the release of certain agents, including bradykinin and nitric oxide, that could trigger signaling in the heart cells, leading to cardio protection -- similar to what is observed after preconditioning,” Kukreja said.

Kukreja gave both oral and intravenous doses of Viagra to adult male New Zealand white rabbits.  In both cases, Viagra reduced the severity of heart damage in the rabbits. The impact was observed in 30 minutes and lasted almost 24 hours after administration of the drug.

Kukreja says more research and extensive clinical trials are needed to understand the molecular reasons that Viagra appears to protect a healthy heart against future damage – research that could take another 2-3 years.  But the implications already are exciting to the medical profession.

“There could be great clinical significance from these findings,” said Dr. George Vetrovec, chair of cardiology at VCU’s School of Medicine and world renowned for his research on coronary artery disease.  “Everything you do to protect the heart muscle reduces the risk of death and improves the outcome for patients with heart attacks.”

Dr. Vetrovec suggested that Viagra one day might be given before surgery to patients who are scheduled for angioplasty or coronary bypass. In addition, he said, it might be given to patients at high, short-term risk of acute myocardial infarction (heart attack), including those patients with such risk factors as high cholesterol, low HDL, hypertension, diabetes or history of smoking.

Kukreja suggested Viagra eventually could be used to protect the brain, liver and other organs against ischemic injury – those injuries that are caused by lack of oxygen.

VCU has applied for a patent on the use of sildenafil for cardio protection.