Viagra shows potential as a cardiopulmonary drug: vasodilatory effects improve heart and lung function by increasing circulation and relaxing blood ve

Sildenafil (Viagra), the much-joked-about drug for erectile dysfunction (ED), is showing serious promise as an effective treatment for a variety of heart, lung and circulatory diseases. Viagra dilates blood vessels throughout the body, mildly decreasing blood pressure, effectively increasing circulation and protecting the heart and lungs from negative reactions to stress.

Physicians continue to be surprised by a growing list of benefits for patients with such complex, difficult-to-treat illnesses as heart failure, pulmonary hypertension and chronic obstructive lung disease (COPD).

HOW AND WHY VIAGRA WORKS

Viagra blocks an enzyme known as phosphodiesterase 5 (PDE5A). This action causes levels of cyclic guanosine monophosphate (cGMP) to rise inside the smooth muscle cells lining veins and arteries. cGMP plays a central role in relaxing blood vessels; an increase in cGMP causes blood vessels to dilate (open).

Interestingly, Viagra was developed to be a cardiac drug, and its ability to cause erections was an incidental finding. Because Viagra proved to have only modest blood pressure lowering effects, it was not expected to have any significant effect on the heart. Experience has proven this theory wrong, and the millions of men who use Viagra for ED have helped bring its cardiopulmonary benefits to light. Following are some key findings of sildenafil (called Revatio for indications other than ED).

GIVING OOMPH TO FAILING HEARTS

Sildenafil increases nitric oxide uptake, which is known to benefit patients with heart failure. Physicians in Australia wondered if this might improve left ventricular function (LV) in weakened hearts. In a double-blind, crossover study, 20 patients with ejection fractions less than 35 percent were given sildenafil or placebo, and their heart failure medications were withheld for at least 12 hours. The drug each patient received was then switched. A variety of tests showed that sildenafil improved the heart's performance by decreasing LV load through several mechanisms. "This can explain the increase in cardiac output and in exercise capacity with sildenafil in patients with heart failure," said the authors in a recent edition of the American Journal of Cardiology.

BLUNTING THE EFFECTS OF STRESS ON THE HEART

One role of cGMP is to help prevent the heart muscle from growing large and weak in response to stress--a condition called cardiac hypertrophy, which can lead to heart failure. Researchers at Johns Hopkins University questioned if sildenafil's ability to increase levels of cGMP could suppress damage caused by this kind of stress. For the study, they recruited 35 healthy volunteers. The volunteers were given multiple tests to determine how their hearts responded to stimulation by dobutamine, a drug that increases heart rate, before and after receiving sildenafil or placebo. Sildenafil prevented damage from occurring during this drug-induced stress without affecting the heart at rest. This study, reported in a recent issue of Circulation, underscored the importance of earlier studies showing the same beneficial effect on hearts stressed by high blood pressure which appeared in Nature Medicine early last year.

LOWERING PULMONARY HYPERTENSION

Many diseases of the heart, lungs and connective tissues, including emphysema and chronic bronchitis, can cause blood pressure to rise in the main artery leading from the heart to the lungs. Symptoms include severe breathlessness and chest pain. This dangerous condition known as pulmonary hypertension is difficult to treat. In a double-blind study, European physicians gave various doses of sildenafil or placebo for 12 weeks to 278 patients with pulmonary hypertension. At the end of this period, patients who took sildenafil were able to walk about 50 yards farther than those who took placebo. The 222 who continued on sildenafil for one year saw a significant drop in pulmonary arterial pressures and continued improvement in their ability to exercise, regardless of the dose of sildenafil they had been taking, according to an article in a recent issue of the New England Journal of Medicine.

In another study, which appeared in a recent issue of Cerebrovascular Disease, of 11 patients with severe pulmonary hypertension, sildenafil was found to improve blood flow to the brain by relaxing its veins and arteries.

ARE ALL ED DRUGS EQUALLY BENEFICIAL?

This question has not been answered. There are two other medications in the same class as Viagra: tadalafil (Cialis) and vardenafil (Levitra). They also cause erections by acting on intracellular cGMP to dilate blood vessels. All three medications can cause side effects in some patients. While some side effects are not serious and stop when the medication wears off, these medications have been known to cause serious side effects, including sudden and permanent loss of vision, fainting and chest pain. Also, these drugs cannnot be combined with certain prescription or over-the-counter medications or herbal supplements, and should not be taken by patients with certain medical conditions.

Of the three ED drugs, only Viagra's effects on the cardiopulmonary system have been studied extensively to date. Many clinical trials are now underway to further define its effects on the conditions mentioned above, as well as on Raynaud's syndrome, scleroderma and other complex diseases. In the future, it appears that Viagra/Revatio may be just what the doctor orders for patients with a wide variety of serious conditions.

DOCTOR'S PERSPECTIVE

WAIT FOR RESULTS OF MORE TRIALS BEFORE WIDESPREAD USE GARY FRANCIS, MD, Head, Section of Cardiology, Cleveland Clinic, Cleveland, OH

"Viagra and other similar drugs are now widely used to treat erectile dysfunction. Their mechanism of action is similar in that they are phosphodiesterase-5 inhibitors. This inhibition leads to smooth muscle relaxation and vasodilation. We have known for years that such drugs may have more selective vasodilator properties on the pulmonary artery tree than on the systemic circuit. The authors have demonstrated that sildenafil (Viagra) improves the heart's performance by diminishing peripheral vascular resistance. There have been numerous studies indicating that oral phosphodiesterase inhibitors may be effective in patients with pulmonary hypertension from a variety of causes, including primary pulmonary hypertension. The improvement in pulmonary artery pressure is translated into improved clinical outcomes, such as less shortness of breath and the ability to do more physical activity. Clearly, such drugs are an option for patients with primary pulmonary hypertension where the development of new therapies has been slow to evolve until the last 5-10 years. It appears to be safe, is less cumbersome than the use of intravenous prostaglandins, and is less expensive than other oral agents that also lower pulmonary vascular resistance. It is unclear whether all phosphodiesterase inhibitor therapies have the same effects in these patients. To date, Viagra has been the most widely studied. Based on the results of these studies, it seems likely that phosphodiesterase inhibitors given in oral form will continue to be studied in patients with peripheral vasospastic diseases including Raynaud's syndrome and scleroderma. However, it would be prudent to wait for the results of randomized controlled trials before embarking on the widespread use of such agents in patients with complex disorders such as this.


COPYRIGHT 2006 Belvoir Media Group, LLC
COPYRIGHT 2007 Gale Group
Health News