Potential Role for Sildenafil in Cardiomyopathy Treatment

WEDNESDAY, May 14 (HealthDay News) -- Enhancing cyclic guanosine monophosphate (cGMP) signaling via genetic avenues as well as with sildenafil (Viagra) protected cardiac contractile function in a mouse model of dystrophin-deficient cardiomyopathy, according to an article published in the May 13 issue of the Proceedings of the National Academy of Sciences.

Maya Khairallah, of the Montreal Heart Institute in Quebec, Canada, and colleagues used both genetic means and pharmacologic approaches to test the hypothesis that enhancement of cGMP signaling had beneficial effects in dystrophin-deficient mouse hearts.

The investigators found that the hearts of dystrophin-deficient mice with overexpression of a gene that increased cGMP levels maintained their contractile performance when perfused ex vivo, while the hearts of dystrophin-deficient mice without this genetic alteration demonstrated severe deterioration in contractile function. In addition, treating dystrophin-deficient mice with sildenafil, which enhances cGMP levels by inhibiting its breakdown, protected cardiac myocytes from damage induced in vivo by increasing the cardiac workload caused by isoproterenol administration.

These data "suggest that defective cGMP signaling within cardiac muscle cells may play a fundamental role in the pathogenesis of the cardiomyopathy associated with dystrophin deficiency," the authors conclude. "In addition, our study raises the possibility that a new therapeutic approach based on cGMP up-regulation with phosphodiesterase-5 inhibitors could be an effective treatment for this condition."

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