Document Detail

Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies.
MedLine Citation:
PMID:  21076027     Owner:  NLM     Status:  MEDLINE    
Cardiac dysfunction is a common cause of death among pediatric patients with mutations in the lysosomal hydrolase α-l-iduronidase (IDUA) gene, which causes mucopolysaccharidosis type I (MPS-I). The purpose of this study was to analyze adrenergic regulation of cardiac hemodynamic function in MPS-I. An analysis of murine heart function was performed using conductance micromanometry to assess in vivo cardiac hemodynamics. Although MPS-I (IDUA(-/-)) mice were able to maintain normal cardiac output and ejection fraction at baseline, this cohort had significantly compromised systolic and diastolic function compared with IDUA(+/-) control mice. During dobutamine infusion MPS-I mice did not significantly increase cardiac output from baseline, indicative of blunted cardiac reserve. Autonomic tone, measured functionally by β-blockade, indicated that MPS-I mice required catecholaminergic stimulation to maintain baseline hemodynamics. Survival analysis showed mortality only among MPS-I mice. Linear regression analysis revealed that heightened end-systolic volume in the resting heart is significantly correlated with susceptibility to mortality in MPS-I hearts. This study reveals that cardiac remodeling in the pathology of MPS-I involves heightened adrenergic tone at the expense of cardiac reserve with cardiac decompensation predicted on the basis of increased baseline systolic volumes.
Nathan J Palpant; Fikru B Bedada; Brandon Peacock; Bruce R Blazar; Joseph M Metzger; Jakub Tolar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-12
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  2014-06-23    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H356-65     Citation Subset:  IM    
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MeSH Terms
Adrenergic beta-1 Receptor Agonists / pharmacology
Blotting, Western
Dobutamine / pharmacology
Heart / drug effects,  physiopathology*
Heart Diseases / metabolism*,  physiopathology*
Linear Models
Mice, Knockout
Mucopolysaccharidosis I / metabolism*,  physiopathology*
Myocardium / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Adrenergic beta-1 Receptor Agonists; 0/AnOV compound; 0/Anthracenes; 3S12J47372/Dobutamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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