Cardiac Uses of Phosphodiesterase-5 Inhibitors

Bryan G. Schwartz, MD; Laurence A. Levine, MD; Gary Comstock, MD; Vera J. Stecher, PhD; Robert A. Kloner, MD, PhD

Disclosures

J Am Coll Cardiol. 2012;59(1):9-15. 

In This Article

Doxorubicin Cardiotoxicity

In a model of chronic (8 weeks) doxorubicin cardiotoxicity, sildenafil protected against doxorubicin-induced apoptosis and preserved left ventricular function.[16] In a mouse model, compared with doxorubicin alone, treatment with doxorubicin plus tadalafil significantly improved survival, fractional shortening, ejection fraction, and hypertrophy.[17] Moreover, tadalafil reduced the incidence of apoptosis and preserved the expression of Bcl-2, which blocks the mitochondrial pathway of apoptosis. Tadalafil also increased cardiac cGMP levels and protein kinase G activity, upregulated mitochondrial superoxide dismutase, and prevented lipid peroxidation. The authors concluded that "tadalafil activated mitochondrial antioxidative and anti-apoptotic mechanisms through up-regulation of cGMP, protein kinase G activity, and mitochondrial superoxide dismutase level without interfering with the chemotherapeutic benefits of doxorubicin".[17] Therefore, prophylactic PDE5Is for patients treated with doxorubicin seems promising and deserves further clinical investigation.

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