O uso precoce de lisinopril e espironolactona preserva a função cardíaca e muscular esquelética em camundongos com distrofia muscular
USA – o lisinopril é uma droga usada no tratamento da hipertensão arterial e insuficiência cardíaca. A espironolactona é um diurético utilizado em insuficiência cardíaca. Os camundongos portadores de uma forma mais grave de distrofia foram tratados a partir dos 4 meses de idade em comparação com os tratados com 8 meses de idade e com os não tratados. Houve melhora das alterações patológicas e da função tanto cardíaca quanto dos músculos esqueléticos, com redução da fibrose. Como são drogas conhecidas e sabidamente úteis no tratamento da doença cardíaca, o seu uso precoce pode ser uma nova estratégia no tratamento da distrofia muscular de Duchenne.
O resumo em inglês pode ser lido abaixo:
(Circulation, 2011) Early Treatment With Lisinopril and Spironolactone Preserves Cardiac and Skeletal Muscle in Duchenne Muscular Dystrophy Mice
Jill A. Rafael-Fortney, Neeraj S. Chimanji, Kevin E. Schill, Christopher D. Martin, Jason D. Murray, Ranjit Ganguly, Jenna E. Stangland, Tam Tran, Ying Xu, Benjamin D. Canan, Tessily A. Mays, Dawn A. Delfín, Paul M.L. Janssen, and Subha V. Raman – USA
Background—Nearly universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death. Because DMD patients show myocardial fibrosis well before functional impairment, we postulated that earlier treatment using drugs with antifibrotic effect may be beneficial.
Methods and Results—Three groups of 10 utrn+/−;mdx, or “het” mice, deficient for dystrophin and haploinsufficient for utrophin with skeletal myopathy and cardiomyopathy that closely mimics clinical DMD were studied. One het group received spironolactone and lisinopril starting at 8 weeks of life (het-treated-8); a second received the same starting at 4 weeks of life (het-treated-4), and the third het group was untreated. At 20 weeks, all mice had normal ejection fractions though circumferential strain rate was abnormal (−0.21±0.08) in untreated hets. This improved to −0.40±0.07 in het-treated-8 mice (P=0.003) and further improved to −0.56±0.10 in het-treated-4 mice (P=0.014 for het-treated-4 versus het-treated-8). Treated mice showed less cardiomyocyte damage, with a 44% reduction in intracardiomyocyte serum immunoglobulin G localization in het-treated-8 mice (P<0.0001) and a further 53% reduction in het-treated-4 mice (P=0.0003 versus het-treated-8); matrix metalloproteinases were similarly reduced. Cardiac, limb, and diaphragm function by ex vivo muscle testing remained at 80% of normal with early treatment compared to a decline to 40% of normal skeletal muscle function without treatment.
Conclusions—These findings offer clinically available medications with proven antifibrotic effect as a new therapeutic strategy in DMD. Early initiation greatly attenuated myocardial disease and, for the first time with these drugs, improved skeletal myopathy. Thus, early initiation of such agents warrants further clinical evaluation to maintain ambulatory, respiratory, and cardiac function for patients with DMD and related myopathies
