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ShareFeb. 15, 2006 — The widely used erectile dysfunction drug Levitra is now the second drug in its class found to protect the heart against tissue damage following acute heart attack, according to a new study by Virginia Commonwealth University researchers.
“Our findings further support the concept that the novel class of phosphodiesterase-5 inhibitors, or PDE-5 inhibitors, including Levitra and Viagra, may have a new utility in cardiac protection, in addition to their well-known use for the management of erectile dysfunction in men,” said Rakesh C. Kukreja, Ph.D., professor of medicine, physiology, biochemistry and emergency medicine at VCU. Kukreja is lead author of the study.
In the study, currently available online and to be published in the March issue of the Journal of Molecular and Cellular Cardiology, Kukreja and his team demonstrated for the first time that pretreatment with a clinically relevant dose of Levitra, generically known as vardenafil, induces a protective effect against heart attack injury by opening the mitochondrial KATP channel in an animal model. The Journal of Molecular and Cellular Cardiology is the official publication of the International Society for Heart Research.
According to Kukreja, PDE-5 is an enzyme responsible for the destruction of cGMP, an intracellular messenger molecule, in heart cells. He said that the mitochondrial KATP channel and cGMP play an important role in preconditioning of the heart following a heart attack. The cGMP also has a hand in the dilation of arteries in the body. PDE-5 inhibitor drugs, such as vardenafil, sildenafil, the generic term for Viagra, and tadalafil, the generic name for Cialis, are able to preserve cGMP, and therefore dilation of the arteries by inhibiting PDE-5.
Vardenafil, like sildenafil, stabilizes the mitochondria and protects against damage of the heart by opening the mitochondrial KATP channels in cardiac cells. Mitochondria are cellular organelles critical for converting oxygen into ATP, the key fuel for cellular function.
“This study provides important information about the mechanism by which the PDE-5 inhibitors work. Furthermore, it is proof that the positive findings of prior studies on sildenafil extend to another PDE-5 inhibitor,” said George Vetrovec, M.D., chair of cardiology at VCU’s School of Medicine, who is internationally recognized for his research on coronary artery disease.
Vetrovec suggested that PDE-5 inhibitors such as sildenafil and vardenafil may one day be given to patients who are at high risk for acute heart attack or prior to undergoing coronary artery bypass surgery to optimize heart protection.
In addition, Kukreja said that the PDE-5 inhibitors may be developed for future use to protect the brain, liver and other organs against ischemic injury – those injuries that are caused by lack of oxygen.
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.
This work was supported by a grant from the National Institutes of Health.
Kukreja collaborated with VCU researchers, Fadi N. Salloum, Ph.D., Ramzi A. Ockaili Ph.D., Michael Wittkamp Ph.D., and Vijay R. Marwaha, Ph.D.
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