Viagra May Protect Hearts of Some Muscular Dystrophy Patients

MONDAY, May 12 (HealthDay News) -- Patients with Duchenne muscular dystrophy often suffer from heart failure, but Viagra might prevent or delay the onset of this condition, a new Canadian study finds.

In experiments with mice, researchers showed that Viagra (sildenafil) improved heart performance by preventing the breakdown of a compound called cGMP, which relaxes smooth muscle.

"Duchenne muscular dystrophy is a crippling disease that affects both skeletal muscle and cardiac muscle," said lead researcher Christine Des Rosiers, a professor of cardiology in the department of nutrition at the University of Montreal. "Currently, there is a need for the development of more effective treatment strategies for patients affected with this disease."

In their experiments, the researchers used mice bred to mimic Duchenne muscular dystrophy. Then the scientists gave the rodents doses of Viagra comparable to those taken by men for erectile dysfunction.

The researchers found that Viagra improved heart function in the mice by preventing the breakdown of cGMP.

In a further experiment, the researchers inserted a gene into the hearts of the mice that increased the production of cGMP. The result: The mice were able to maintain normal heart function.

The findings are published in this weeks issue of the Proceedings of the National Academy of Sciences .

"Our findings substantiate benefits for the dystrophic heart using a pharmacological approach, namely with sildenafil, which is safe, well-tolerated and currently available for clinical use," Des Rosiers said. "Hence, this could provide the basis for a new avenue for the treatment. Furthermore, the benefits of this therapeutic approach would be expected to extend beyond the heart to affected skeletal muscle and other tissues."

Dr. Valerie A. Cwik, medical director and vice president of research at the Muscular Dystrophy Association, said there's a need for new approaches to the treatment of heart failure in patients with Duchenne and other forms of muscular dystrophy.

"The findings presented by these authors are interesting and certainly have potential clinical implications for the various forms of dystrophinopathy [heart damage]," she said, adding that heart failure is a major cause of illness and death in late-stage Duchenne muscular dystrophy.

"At the present time, there is no consensus or standard of care for optimal management of the cardiac complications of dystrophinopathies, and further research in this area is clearly needed," Cwik said.

While Viagra hasn't been tested in humans to see if it benefits muscular dystrophy patients, it has been available for years and appears to be safe, Cwik noted.

12 May, 2008
http://www.nlm.nih.gov/medlineplus/news/fullstory_64515.html

 The erectile dysfunction drug Viagra may have found a new, potentially life-saving use in hospital pediatric intensive care units, researchers report.

Australian researchers gave the drug to 15 babies with congenital heart disease who were being weaned from inhaled nitric-oxide therapy, a treatment that ICUs use to help these infants survive. The researchers found that a dose of Viagra prevented a common life-threatening complication called rebound pulmonary hypertension. They also found that it significantly reduced the amount of time the babies spent on mechanical ventilation and in the ICU. "Rebound pulmonary hypertension is a very common problem," said Dr. Steven Abman of The Children's Hospital in Denver, who was not part of the study. "This is the most rigorous study that's ever been done to demonstrate that Viagra can prevent this complication." The study results were published in the November issue of the American Journal of Respiratory and Critical Care Medicine. Viagra is useful for treating both erectile dysfunction and preventing rebound pulmonary hypertension because it affects pathways involved in both conditions. "Viagra enhances the body's levels of cyclic-GMP, a naturally occurring substance that relaxes arteries and reduces their pressure, which is why its primary indication is for men with erectile dysfunction," explained the study's lead researcher, Dr. Lara Shekerdemian of the Pediatric Intensive Care Unit at the Royal Children's Hospital in Melbourne. "However, cyclic-GMP is abundant in the lungs and is the molecule via which nitric oxide acts as a dilator of pulmonary arteries," Shekerdemian said. "That's why its use was explored in the setting of pulmonary hypertension in the newborn." In the study, Shekerdemian and colleagues gave a single dose of Viagra to 15 infants with congenital heart disease who were undergoing withdrawal from nitric oxide, which is used to relax pulmonary blood vessels in mechanically ventilated lungs. Another 14 infants undergoing withdrawal were given placebo. None of the Viagra-treated infants developed rebound pulmonary hypertension compared to 10 of the placebo-treated infants. After more than 24 hours, all of the infants who developed rebound hypertension were given Viagra during a subsequent and successful attempt to wean them from nitric oxide. The Viagra-treated infants also spent less total time on a mechanical ventilator than the placebo-treated infants -- a little over 28 hours compared to 98 hours -- and had a considerably shorter stay in the intensive care unit (47.8 hours vs. 189 hours). "Although we expected to see an avoidance of rebound, we were not expecting to see these additional benefits," Shekerdemian said. "Any intervention that smoothes their course in the intensive-care unit would have at least a short-term positive influence on their recovery from their underlying condition." Unless there's some reason for not using Viagra, Shekerdemian said that it should be routinely used as infants are weaned from nitric oxide. "We certainly do so now in our pediatric intensive-care unit," she said. Many hospitals are already doing just that. "I think it already has become standard clinical practice, because the idea of using Viagra for this is not new," Abman said. "What's new is that this is the first study to look at it with a nice protocol in which they randomized patients and controlled in a blinded way. So it verifies what we've already been doing in clinical practice." Shekerdemian and her team are now conducting a similar study in the Royal Children's Hospital's Neonatal Intensive-Care Unit to see if Viagra can prevent rebound pulmonary hypertension in premature infants.

2 Nov, 2006
http://www.nlm.nih.gov/medlineplus/news/fullstory_40844.html

 Viagra Helps COPD Patients Control Pulmonary Blood Pressure

The drug sildenafil, popularly known as Viagra, may help people with chronic obstructive pulmonary disease control the illness-related blood pressure spikes in the heart's pulmonary artery, a new study found.

The medication, in addition to its use as a popular treatment for impotence, has already been approved by the U.S. Food and Drug Administration for the treatment of the chronic version of such blood pressure spikes, known as pulmonary arterial hypertension (PAH). The drug has been marketed specifically for this purpose under the trade name Revatio. Another drug -- bosentan -- is also approved for similar purposes.

The new research suggests that sildenafil may help all chronic obstructive pulmonary disease (COPD) patients -- even those not diagnosed with full-blown PAH -- who experience potentially dangerous pulmonary arterial blood pressure increases both at rest and following exercise.

The research was led by Dr. Sebastiaan Holverda of the department of pulmonary medicine at VU University Medical Center in Amsterdam, the Netherlands. Holverda and his VU colleagues were to present their findings Wednesday at a Salt Lake City meeting organized by the journal Chest.

According to the American Lung Association, COPD is actually a catch-all for two lung diseases that often strike in tandem -- chronic bronchitis and emphysema. In both cases, airflow is obstructed, impeding normal breathing.

Smoking is the leading cause of COPD, responsible for between 80 percent and 90 percent of all cases in the United States. More than 11 million Americans are estimated to have the illness, and more than 122,000 die from it each year. Women appear to be slightly more at risk than men.

There's no known cure for the disease, and medications primarily take aim at symptom relief and slowing the progressive disability the illness brings.

Pulmonary hypertension -- the incurable condition of continuous high blood pressure in the pulmonary artery located in the right ventricle of the heart -- is one of many serious complications that can strike COPD patients. PAH causes the artery, which is responsible for delivering blood from the heart to the lungs, to work harder than normal. A weakening of the heart muscle can ensue over time, increasing the risk of heart failure and even death.

The Dutch researchers noted that pulmonary hypertension is typically mild to moderate among COPD patients but is particularly aggravated while exercising.

Faced with the combined COPD-PAH threat, the Dutch team explored the potential benefit of treating at-risk chronic obstructive pulmonary disease patients with sildenafil both while at rest and during exercise. The drug works by shifting the activity of an enzyme called phosphodiesterase, reducing arterial blood pressure by dilating the smooth muscle of blood vessels that line the lungs. As these vessels expand, blood flow increases, the researchers explained.

The study authors focused on 12 patients who had been diagnosed with chronic obstructive pulmonary disease and were suspected of having PAH. Throughout the study, right heart blood pressure was tracked among all 12 patients by inserting a thin plastic tube into the pulmonary artery -- a procedure known as cardiac catheterization. Cardiac blood pressure was measured at rest and just after all the patients cycled for three minutes.

Then, the study participants were given 50 milligrams of oral sildenafil; 45 minutes later, resting and post-exercise blood pressure readings were taken again.

Holverda and his colleagues found that half the patients had PAH. But, both non-PAH and PAH patients experienced significant cardiac blood pressure increases when exercising.

Sildenafil appeared to control such increases after exercise, reigning in pulmonary blood pressure to markedly lower levels -- higher than at rest, but lower than non-medicated post-exercise readings. And, the non-PAH patients appeared to experience pulmonary blood pressure reductions after taking the drug, both while resting and exercising.

The authors concluded that the drug may help COPD patients -- whether they have developed PAH or not -- quickly control their pulmonary blood pressure in some situations.

Dr. Bartolome R. Celli, chief of pulmonary care at St. Elizabeth's Medical Center in Boston, applauded the Dutch study but called for more research.

"Pulmonary arterial pressure -- when it is elevated -- is a poor prognostic sign and reducing its levels should be of help," he said. "However, more testing is needed to see if those changes in pulmonary arterial pressure are translated into better clinical outcomes and not into any unwanted side effects."

25 Oct, 2006
http://www.nlm.nih.gov/medlineplus/news/fullstory_40520.html