size matters. A mouse heart stays healthy (below) when treated with sildenafil, while his counterpart does.
The blockbuster drug sildenafil, sold as Viagra for men with erectile dysfunction, may have another benefit: preventing and reversing heart failure. In mice, the drug blunted an enzyme thought to help stimulate an oversized weakened heart. Mice with induced heart failure improved dramatically, but the approach has not been tested in humans.
Pfizer sildenafil originally developed to treat chest pain called angina. The drug blocks the phosphodiesterase 5A (PDE5A), a dispersed enzyme through smooth muscle cells in the body. Blocking PDE5A prevents the accumulation of another enzyme called cGMP, which in turn causes the arteries to dilate. narrowed arteries, as well as other potentially controlled by PDE5A forces can also play a role in heart failure.
Cardiologists David Kass and Eiki Takimoto of Johns Hopkins University, and colleagues decided to test the effects of sildenafil on the heart. The team recently found PDE5A in the heart muscle. Blocking with sildenafil, they thought, can inhibit the molecular cascade that leads to heart failure. Thus, the team subjected mice to surgery which constriction major cardiac artery and gave some of sildenafil animals. Within 9 weeks the animals who had acquired the drug had a heart much healthier, with improvements such as 67% less fibrosis, animals without drugs, the team reports online in the January 24 Nature Medicine .
to see whether sildenafil could reverse untreated heart failure, Kass group performed the same operation on another set of mouse, then waited 7-10 days. By then, the heart mass of the animals had reached 63%, a key sign of heart weakness. Half of the animals were sildenafil for 2 weeks and the other half received a placebo. Echocardiograms showed that in the treated animals, heart mass decreased gradually. The results may seem counterintuitive given that sildenafil carries warnings that it can cause heart problems, but says Kass, which is because the drug interacts with cardiac treatments such as nitroglycerin, which could trigger blood pressure drops .
"This drug is close the loop," says Robert Kloner, director of research at the Heart Institute at Good Samaritan Hospital and a faculty member of the University of Southern California, referring to Pfizer. Pfizer's early angina tests recently asked the Food and Drug Administration for approval to treat a disorder of life hazard, primary pulmonary hypertension.
Kloner called the new discovery "intriguing." It is also controversial: There is a debate about whether PDE5A is really present in the cardiac muscle, Kloner said, although several groups have recently detected there
Related Sites
information on heart disease. the American heart Association
information on cardiac hypertrophy
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