© 2008 European Society of Cardiology
Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart
a Department of Cardiology, Aarhus University Hospital Skejby, Denmark
b The Water and Salt Research Centre, Institute of Anatomy, Aarhus University Denmark
c Department of Anaesthesiology and Intensive Care, Aarhus University Hospital Skejby, Denmark
* Corresponding author. Department of Cardiology, B-research, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, Aarhus, Denmark. Tel.: +45 89496229; fax: +45 26363226. E-mail address: asgerandersen{at}gmail.com (A. Anderson).
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Abstract |
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Background: Sustained pressure overload of the right ventricle (RV) causes RV hypertrophy and failure. Cyclic-GMP has previously been shown to modulate left ventricular hypertrophy.
Aim: To evaluate the effects of sildenafil, a phosphodiesterase-5 (PDE5) inhibitor elevating c-GMP, on myocardial hypertrophy and function in rats with RV hypertrophy.
Methods: Rats were pulmonary trunk banded (PTB) and randomized to receive sildenafil (SIL) or vehicle (VEC) for three (n = 14) and nine weeks (n = 18). In addition, rats with established RV hypertrophy were randomized to SIL or VEC (n = 17) three weeks after PTB. Right ventricular function was evaluated by echocardiography and RV hypertrophy by histology and RV weight.
Results: Sildenafil failed to inhibit the development of RV hypertrophy when given for both 3 and 9 weeks. On the contrary, sildenafil increased RV hypertrophy after 3 weeks (RV/bodyweight: SIL 0.099±0.016 vs. VEC 0.081±0.011; p<0.05) and total heart weight after 9 weeks (SIL 1.05±0.10 vs. VEC 0.93±0.08g; p<0.05). Sildenafil also failed to reverse established RV hypertrophy, but significantly improved RV myocardial function as measured by Tricuspid Annular Plane Systolic Excursion (TAPSE: SIL 1.8±0.027 vs. VEC 1.39±0.037 mm; p<0.05).
Conclusion: PDE5 inhibition by sildenafil failed to prevent or reverse RV hypertrophy in rats operated by pulmonary trunk banding. It actually increased RV hypertrophy and improved RV contractile function when given to rats with established RV hypertrophy.
Key Words: Pulmonary hypertension • Right ventricular hypertrophy • Sildenafil • Pulmonary trunk banding • Echocardiography • Right ventricular failure
Received March 7, 2008; Revised June 27, 2008; Accepted September 30, 2008
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