Enhancement of myocardial and vascular function after phosphodiesterase-5 inhibition in a rat model.

Background: Recent studies have shown the potential of PDE-5 inhibition on acute and chronic heart failure. Nevertheless it remained unclear, how far load-reducing properties and direct effects on myocardial contractility are responsible for these observations. In the present study, we investigated the effects of vardenafil on myocardial contractility and vascular function in a dose-response study.

Methods: We performed left ventricular pressure-volume analysis in young adult rats by using a Millar microtip conductance catheter. Pressure-volume loops were recorded before and after intravenous injection of vardenafil (3, 10, 30, 100, 300 μg/kg, n = 6/group).

Results: Treatment with vardenafil resulted in a significant (p < 0.05) increase in the load-independent cardiac contractility parameters reaching its maximum at the dose of 100μg/kg (ESPVR: 2.15 ± 0.15 vs. 3.29 ± 0.26 mm Hg/μL; PRSW: 93.28 ± 4.04 vs. 134.90 ± 6.27 mm Hg; peak positive dP/dt/EDV: 38.73 ± 7.97 vs. 53.02 ± 3.74 mm Hg·s-1·µL-1; before versus after 100 μg/kg vardenafil). Results of the in vitro organ-bath experiments showed an augmented vasorelaxation of precontracted aortic rings after vardenafil treatment.

Conclusion: Our data supports the hypothesis that the usage of vardenafil as "inodilators" could have beneficial effects in heart failure patients.