Monday, October 24, 2005

Hilarious Journal Articles #19: Viagra Helps the Heart Respond to Stress

Apparently Viagra, a phosphodiesterase inhibitor, was originally designed as a medication for the heart, but it failed in initial trials. It was shelved until someone realized that Viagra's unusual side effect of improving erections might be potentially useful.

Now, an article in Circulation has resurrected interest in the cardiovascular benefits of Viagra. From Forbes:
Viagra, famous for improving men's sexual function, also appears to reduce the effects of hormonal stress on the heart by 50 percent, claims a report by researchers at Johns Hopkins University...

"Unlike what was previously thought, drugs like Viagra can in fact alter heart function," said lead researcher Dr. David Kass, a professor of medicine at Johns Hopkins. "It alters it particularly when the heart is stimulated by hormones..."

Kass noted that his group is starting a clinical trial to see if Viagra can be effective in patients with heart failure. "If you gave a drug like Viagra not just acutely, but chronically, you might be able to improve heart function and reduce the chronic stress response in patients with hypertrophy..."
From the article in Circulation, "Sildenafil Inhibits ß-Adrenergic–Stimulated Cardiac Contractility in Humans":
Background— Sildenafil inhibits phosphodiesterase 5 (PDE5A) to elevate intracellular cGMP and to induce vasodilation. This effect has led to its use for treating erectile dysfunction. Although its influence on rest heart function has appeared minimal, recent animal studies suggest that sildenafil can have potent effects on hearts stimulated by ß-adrenergic or pressure overloads. We therefore tested whether sildenafil blunts dobutamine-stimulated cardiac function in humans.

Methods and Results— Thirty-five healthy volunteers underwent a randomized, double-blind, placebo-controlled study in which cardiac function was assessed in response to dobutamine before and after oral sildenafil (100 mg, n=19) or placebo (n=16). Echo Doppler and noninvasive blood pressure data yielded load-independent contractility indexes (maximal power index and end-systolic elastance), ejection fraction, and measures of diastolic function. In the initial dobutamine test, systolic and diastolic function improved similarly in both treatment groups (eg, peak power index rose 80±28% in the placebo group and 82±31% in the sildenafil group; P=NS). However, in subjects who then received sildenafil, their second dobutamine response was significantly blunted, with peak power, ejection fraction, and end-systolic elastance changes reduced by 32±34%, 66±64%, and 56±63%, respectively (each P<0.001 versus the initial response). This contrasted to the placebo group, which displayed similar functional responses with both dobutamine tests. Sildenafil treatment did not significantly alter diastolic changes induced by dobutamine compared with results with placebo.

Conclusions— PDE5A inhibition by sildenafil blunts systolic responses to ß-adrenergic stimulation. This finding supports activity of PDE5A in the human heart and its role in modifying stimulated cardiac function.
(According to another article, Viagra also helps save endangered species.)

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