Document Detail


Early Right Ventricular Fibrosis and Reduction in Biventricular Cardiac Reserve in the Dystrophin-Deficient mdx Heart.
MedLine Citation:
PMID:  25485898     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Duchenne muscular dystrophy (DMD) is a progressive disease of striated muscle deterioration. Respiratory and cardiac muscle dysfunction are particularly clinically relevant because they result in the leading causes of death in DMD patients. Despite the clinical and physiological significance of these systems, little has been done to understand the cardio-respiratory interaction in DMD. We show here that prior to the onset of global cardiac dysfunction, dystrophin-deficient mdx mice have increased cardiac fibrosis with the right ventricle being particularly affected. Using a novel biventricular cardiac catheterization technique coupled with cardiac stress testing, we demonstrate that both the right and left ventricles have significant reductions in both systolic and diastolic function in response to dobutamine. Unstimulated cardiac function is relatively normal except for a significant reduction in the ventricular pressure transient duration compared to controls. These biventricular analyses also reveal the absence of a dobutamine-induced increase in isovolumic relaxation in the right ventricle of control hearts. Simultaneous assessment of biventricular pressure demonstrates a dobutamine-dependent enhancement of coupling between the ventricles in control mice, which is absent in mdx mice. Further, studies probing the passive-extension properties of the left ventricle demonstrate that the mdx heart is significantly more compliant compared to age matched C57BL/10 hearts, which have an age-dependent stiffening that is completely absent from dystrophic hearts. These new results indicate that right ventricular fibrosis is an early indicator of the development of dystrophic cardiomyopathy, suggesting a mechanism by which respiratory insufficiency may accelerate the development of heart failure in DMD.
Authors:
Tatyana A Meyers; DeWayne Townsend
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-5
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-8     Completed Date:  -     Revised Date:  2014-12-9    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  ajpheart.00485.2014     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
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