Sildenafil citrate does not affect cardiac contractility in human or dog heart

SUMMARY

Objective: This study evaluated whether sildenafil citrate, an oral treatment for erectile dysfunction and a selective inhibitor of phosphodiesterase type 5 (PDE5) with modest vasodilating properties, affects cardiac contractility in vitro.

Research design and methods: Slices of freshly obtained human (n = 2) or dog (n = 3) atrial appendage were suspended in organ baths containing Krebs—Ringer bicarbonate buffer (pH 7.4, 37°C) bubbled continuously with 95% O2 and 5% CO2, and isometric tension was recorded using a Gould physiograph. Contractions were elicited by 1-Hz electric pacing. After 15min of equilibration, 1\M sildenafil was added to the bath, followed 15min later (human and dog) by 5|iM epinephrine, an inotropic agent, and 10min later (dog) by 88|iM 3-isobutyl-1 -methylxanthine

(IBMX), a nonselective PDE inhibitor. In a separate experiment, cyclic guanosine monophosphate levels and PDE, protein kinase G, and protein kinase A activities were determined.

Results: Addition of 1 |iM sildenafil to isolated dog or human atrial tissue had no significant effect on force of cardiac contraction, whereas epinephrine produced a robust increase in contractile force in the same muscle strip. The addition of IBMX produced a marked stimulation of contractile force in dog atrial tissue. Very low amounts of PDE5 were found in extracts of human heart, consistent with its known primary location in the smooth muscle of systemic vasculature.

Conclusions: Sildenafil is unlikely to directly produce inotropic effects on cardiac muscle in patients being treated for erectile dysfunction.

Key words: :

• Cardiac contractility
• Erectile dysfunction
• Phosphodiesterase
• Sildenafil citrate