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Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart.
Eur J Heart Fail. 2008 Dec; 10(12):1158-65.EJ

Abstract

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+/-0.08 g; 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 1.85+/-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.

Authors+Show Affiliations

Department of Cardiology, Aarhus University Hospital, Skejby, Denmark. asgerandersen@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19004667

Citation

Andersen, Asger, et al. "Effects of Phosphodiesterase-5 Inhibition By Sildenafil in the Pressure Overloaded Right Heart." European Journal of Heart Failure, vol. 10, no. 12, 2008, pp. 1158-65.
Andersen A, Nielsen JM, Peters CD, et al. Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. Eur J Heart Fail. 2008;10(12):1158-65.
Andersen, A., Nielsen, J. M., Peters, C. D., Schou, U. K., Sloth, E., & Nielsen-Kudsk, J. E. (2008). Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. European Journal of Heart Failure, 10(12), 1158-65. https://doi.org/10.1016/j.ejheart.2008.09.016
Andersen A, et al. Effects of Phosphodiesterase-5 Inhibition By Sildenafil in the Pressure Overloaded Right Heart. Eur J Heart Fail. 2008;10(12):1158-65. PubMed PMID: 19004667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart. AU - Andersen,Asger, AU - Nielsen,Jan Møller, AU - Peters,Christian Daugaard, AU - Schou,Uffe Kjaer, AU - Sloth,Erik, AU - Nielsen-Kudsk,Jens Erik, Y1 - 2008/11/12/ PY - 2008/03/07/received PY - 2008/06/27/revised PY - 2008/09/30/accepted PY - 2008/11/14/pubmed PY - 2009/3/12/medline PY - 2008/11/14/entrez SP - 1158 EP - 65 JF - European journal of heart failure JO - Eur J Heart Fail VL - 10 IS - 12 N2 - 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+/-0.08 g; 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 1.85+/-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. SN - 1388-9842 UR - https://www.unboundmedicine.com/medline/citation/19004667/Effects_of_phosphodiesterase_5_inhibition_by_sildenafil_in_the_pressure_overloaded_right_heart_ L2 - https://doi.org/10.1016/j.ejheart.2008.09.016 DB - PRIME DP - Unbound Medicine ER -