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Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

BACKGROUND: Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. ME...

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Autores principales: Spurney, Christopher F, Guerron, Alfredo D, Yu, Qing, Sali, Arpana, van der Meulen, Jack H, Hoffman, Eric P, Nagaraju, Kanneboyina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123649/
https://www.ncbi.nlm.nih.gov/pubmed/21575230
http://dx.doi.org/10.1186/1471-2261-11-20
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author Spurney, Christopher F
Guerron, Alfredo D
Yu, Qing
Sali, Arpana
van der Meulen, Jack H
Hoffman, Eric P
Nagaraju, Kanneboyina
author_facet Spurney, Christopher F
Guerron, Alfredo D
Yu, Qing
Sali, Arpana
van der Meulen, Jack H
Hoffman, Eric P
Nagaraju, Kanneboyina
author_sort Spurney, Christopher F
collection PubMed
description BACKGROUND: Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. METHODS: Three month old female mdx mice were exposed to the β(1 )receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining. RESULTS: BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers. CONCLUSIONS: This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.
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spelling pubmed-31236492011-06-26 Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice Spurney, Christopher F Guerron, Alfredo D Yu, Qing Sali, Arpana van der Meulen, Jack H Hoffman, Eric P Nagaraju, Kanneboyina BMC Cardiovasc Disord Research Article BACKGROUND: Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. METHODS: Three month old female mdx mice were exposed to the β(1 )receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining. RESULTS: BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers. CONCLUSIONS: This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice. BioMed Central 2011-05-16 /pmc/articles/PMC3123649/ /pubmed/21575230 http://dx.doi.org/10.1186/1471-2261-11-20 Text en Copyright ©2011 Spurney et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Spurney, Christopher F
Guerron, Alfredo D
Yu, Qing
Sali, Arpana
van der Meulen, Jack H
Hoffman, Eric P
Nagaraju, Kanneboyina
Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title_full Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title_fullStr Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title_full_unstemmed Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title_short Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice
title_sort membrane sealant poloxamer p188 protects against isoproterenol induced cardiomyopathy in dystrophin deficient mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123649/
https://www.ncbi.nlm.nih.gov/pubmed/21575230
http://dx.doi.org/10.1186/1471-2261-11-20
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