Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies

Nathan J. Palpant, Fikru B. Bedada, Brandon Peacock, Bruce R. Blazar, Joseph M. Metzger, Jakub Tolar

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)H356-H365
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1
StatePublished - Jan 2011


  • Cardiomyopathy
  • Hurler syndrome
  • Phosphorylation


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