title: Ibuprofen plus isosorbide dinitrate treatment in the mdx mice ameliorates dystrophic heart structure.
abstract: BACKGROUND
  Co-administration of ibuprofen (IBU) and isosorbide dinitrate (ISDN) provides synergistic beneficial effects on dystrophic skeletal muscle. Whether this treatment has also cardioprotective effects in this disease was still unknown.
  
  
  OBJECTIVE
  To evaluate the effects of co-administration of IBU and ISDN (a) on left ventricular (LV) structure and function, and (b) on cardiac inflammatory response and fibrosis in mdx mice.
  
  
  METHODS
  Three groups of mice were studied: mdx mice treated with IBU (50 mg kg⁻¹)+ISDN (30 mg kg⁻¹) administered daily in the diet, mdx mice that received standard diet without drugs and wild type aged-matched mice. Animals were analysed after 10-11 months of treatment. Structural and functional parameters were evaluated by echocardiography while histological analyses were performed to evaluate inflammatory response, collagen deposition, cardiomyocyte number and area.
  
  
  RESULTS
  Treatment for 10-11 months with IBU+ISDN preserved LV wall thickness and LV mass. Drug treatment also preserved the total number of cardiomyocytes in the LV and attenuated the increase in cardiomyocyte size, when compared to untreated mdx mice. Moreover, a trend towards a decreased number of inflammatory cells, a reduced LV myocardial interstitial fibrosis and an enhanced global LV function response to stress was observed in treated mdx mice.
  
  
  CONCLUSIONS
  Treatment for 10-11 months with IBU+ISDN is effective in preventing the alterations in LV morphology of mdx mice while not reaching statistical significance on LV function and cardiac inflammation.
authors: Division of Regenerative Medicine, Ospedale San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy. sciorati.clara@hsr.it
authors: Clara
authors: C
authors: Sciorati
authors: Lidia
authors: L
authors: Staszewsky
authors: Vanessa
authors: V
authors: Zambelli
authors: Ilaria
authors: I
authors: Russo
authors: Monica
authors: M
authors: Salio
authors: Deborah
authors: D
authors: Novelli
authors: Giuseppe
authors: G
authors: Di Grigoli
authors: Rosa Maria
authors: RM
authors: Moresco
authors: Emilio
authors: E
authors: Clementi
authors: Roberto
authors: R
authors: Latini
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002302:Cardiac Output; D007052:Ibuprofen / Q000008:administration & dosage*; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D013318:Stroke Volume; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020030:Nitric Oxide Donors; D007548:Isosorbide Dinitrate; D007052:Ibuprofen