送交者: Latino2 于 2005-1-26, 12:56:12:
Viagra for Broken Hearts?
The blockbuster drug sildenafil, marketed as Viagra to men with erectile
dysfunction, may have another benefit: preventing and reversing heart failure.
In mice, the drug blunted an enzyme thought to help spur an oversized,
weakened heart. Mice with induced heart failure improved dramatically, but
the approach has not yet been tested in humans.
Pfizer originally developed sildenafil to treat chest pain called angina.
The drug blocks phosphodiesterase 5A (PDE5A), an enzyme scattered across
smooth muscle cells throughout the body. Blocking PDE5A prevents the buildup
of another enzyme called cyclic GMP, which in turn forces arteries to dilate.
Constricted arteries, along with other forces potentially controlled by
PDE5A, can also play a role in heart failure.
Cardiologists David Kass and Eiki Takimoto of Johns Hopkins University,
and their colleagues decided to test sildenafil's effects on the heart.
The team had recently found PDE5A in heart muscle. Blocking it with sildenafil,
they thought, might inhibit the molecular cascade that leads to heart failure.
So the team subjected mice to surgery that constricted a major cardiac
artery and gave some of the animals sildenafil. Within 9 weeks, the animals
who had gotten the drug had markedly healthier hearts, with improvements
such as 67% less fibrosis, than the animals without the drug, the team reports
in the 24 January online Nature Medicine.
To see whether sildenafil could reverse untreated heart failure, Kass's
group performed the same surgery on another set of mice, and then waited
7 to 10 days. By then, the animals' heart mass had soared 63%, a key sign
of heart weakness. Half the animals got sildenafil for 2 weeks, and half
received a placebo.
Echocardiograms showed that in the treated animals, heart mass gradually
declined. The results may seem paradoxical given that sildenafil carries
warnings that it can cause heart trouble, but, says Kass, that's because
the drug interacts with cardiac treatments like nitroglycerine, potentially
triggering drops in blood pressure.
"This drug is coming full circle," says Robert Kloner, director of research
at the Heart Institute at Good Samaritan Hospital and a faculty member at
the University of Southern California, referring to Pfizer's early angina
testing. Pfizer recently applied to the Food and Drug Administration for
approval to treat a related life-threatening disorder, primary pulmonary
hypertension.
Kloner calls the new finding "intriguing." It's also controversial: There's
some debate over whether PDE5A is really present in heart muscle, Kloner
says, though several groups have recently detected