Sildenafil, which had been thought to have only peripheral vascular effects, may have a significant, direct cardiac benefit through reduction of beta-adrenergic stimulation of myocardial contractility, according to an article published online October 24th by Circulation.

“Sildenafil effectively puts a ‘brake’ on chemical stimulation of the heart,” said David Kass, MD, a professor at The Johns Hopkins University School of Medicine and its Heart Institute and senior author of the study.

In the current work, 35 healthy men and women, with an average age of 30 years and no previous signs of coronary artery disease, participated in the six-month study. Within a three-hour timeframe, each participant received two separate injections of dobutamine (5 micrograms per kilogram for five minutes). Between injections, study participants were randomly assigned to a group that was treated with sildenafil (100 milligrams taken orally) or to a group given placebo. All participants were then given a second dobutamine injection to see what effects sildenafil or placebo had on the heart.

Measurements of heart function were made before and after each injection, including blood pressure readings, electrocardiograms and echocardiograms, as well as blood samples to confirm relatively equal levels of sildenafil and other enzymes.
Results showed that each dobutamine injection produced inotropic effects. Kass said, “This stimulation is similar to the way the nervous system normally increases heart function when triggered by emotional or exercise stress, or in diseases such as heart failure.”

After the first injection of dobutamine, the force of heart contraction increased by 150 percent in both groups. In the placebo group, this increase repeated itself after the second injection. However, in the group treated with sildenafil, the increased heartbeat was slowed by 50 percent, resulting in a smaller increase in blood flow and blood pressure.

Between injections, heart function was not altered in the sildenafil group, demonstrating the absence of adverse side effects on the resting human heart.
“Knowing more about the effects of sildenafil on heart function will allow for safer evaluation of its use as a treatment for heart problems,” said Kass. “Until now, it was widely thought that drugs like sildenafil had no effects on the human heart and that its only purpose was vasodilation in the penis and the lungs.

“Our results set the stage for further studies of sildenafil’s immediate and long-term effects on the heart and its ability to modify other neurohormonal and stress stimuli, including adrenaline and hypertension,” he added.

Although the precise biological actions of sildenafil in the heart are not fully understood, the drug is known to work by stopping the action of an enzyme called phosphodiesterase 5 (PDE5A). This enzyme is involved in the breakdown of cyclic GMP, which helps control stresses and limit overgrowth in the heart. PDE5A is also the biological pathway blocked in the penis by sildenafil to prevent the relaxation of blood vessels and maintain erections.