Sildenafil prevents anti-cancer drug induced heart damage

Apr 5 2005

Virginia Commonwealth University researchers have found that the popular impotence drug Viagra prevents damage to the heart from a potent chemotherapeutic agent frequently used in the treatment of breast cancer, leukemia and sarcomas.

In the April 5 issue of Circulation: Journal of the American Heart Association, researchers demonstrated for the first time that administration of clinically relevant doses of Viagra, generically known as sildenafil citrate, one-hour prior to the administration of the anti-cancer drug doxorubicin (DOX) prevented heart damage at the cellular level. The research also showed that the impotence drug also prevented dilated cardiomyopathy and heart failure in a chronic mouse model. Furthermore, researchers observed a reduction of DOX-induced cell death, an improvement of heart function, and a reduction of electrophysiological abnormalities associated with heart sickness.

"Our research holds promise for the potential use of sildenafil in patients receiving DOX as part of their chemotherapeutic regimen with the goal of reducing the incidence of DOX cardiomyopathy," said the lead author of the study, Rakesh C. Kukreja, Ph.D., professor of medicine, physiology and biochemistry at VCU.

"Viagra stabilizes the mitochondria and protects against free-radical damage of the mitochondria and heart dysfunction caused by treatment with DOX by opening the mitochondrial KATP channels in cardiac cells," said Kukreja.

Mitochondria are cellular organelles critical for converting oxygen into ATP, the key fuel for cellular function. According to Kukreja, free radicals generated in the mitochondria of cardiac cells by DOX lead to the break down of regular cellular function, resulting in programmed cardiac cell death. Over time, cell death has been linked to decreased heart function or heart failure.

DOX is an effective chemotherapeutic agent commonly used in the treatment of many blood and solid tumor malignancies. Despite DOX's clinical efficacy for treatment of cancer, its use is associated with a delayed and progressive cardiomyopathy, often presenting several years after treatment cessation.

"Viagra is able to protect the heart from damage that would otherwise disrupt normal cellular functioning," Kukreja said.

Kukreja and his colleagues began studying sildenafil in 2002 as part of ongoing research into "preconditioning," 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. In papers published in the September 2002 issue of the American Journal of Physiology and the March 2003 issue of Circulation Research, Kukreja and his colleagues observed a powerful, protective effect of Viagra in the heart during experimental heart attacks in animal models.

http://www.vcu.edu/