Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy
| Autor: | Jose M. Otero, Matthew F. Sullivan, Victor Chu, James P. Morgan, Thomas G. Hampton, Orlando Lopez, Ivo Amende |
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| Rok vydání: | 2002 |
| Předmět: |
musculoskeletal diseases
Atropine Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty mdx mouse Physiology Duchenne muscular dystrophy Muscarinic Antagonists Nitric Oxide Synthase Type I Baroreflex Autonomic Nervous System Nitric Oxide Cellular and Molecular Neuroscience Electrocardiography Mice Heart Rate Physiology (medical) Internal medicine Heart rate medicine Animals PR interval Mice Knockout Neurons business.industry Muscarinic antagonist Heart musculoskeletal system medicine.disease Mice Inbred C57BL Muscular Dystrophy Duchenne Autonomic nervous system Endocrinology Phenotype Mice Inbred mdx Neurology (clinical) Nitric Oxide Synthase business medicine.drug |
| Zdroj: | Musclenerve. 26(4) |
| ISSN: | 0148-639X |
| Popis: | The mdx mouse is a model of Duchenne muscular dystrophy (DMD). As many DMD patients die of cardiac failure, we investigated whether mdx mice exhibited clinically relevant cardiac phenotypes. We applied a recently developed method for noninvasively recording electrocardiograms (ECGs) to study male mdx mice (n = 15) and control mice (n = 15). The mdx mice had significant tachycardia and decreased heart rate variability, consistent with observations in DMD patients. Heart rate was nearly 15% faster in mdx mice than control mice (P < 0.05). The rate-corrected QT interval duration and PR interval were shorter in mdx compared to control mice (P < 0.05). The muscarinic antagonist atropine significantly increased heart rate and decreased PR interval in C57 mice. In contrast, atropine significantly decreased heart rate and increased PR interval in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. Baseline ECGs and contrary responses to muscarinic blockade by atropine in mice deficient in neuronal nitric oxide synthase (nNOS) suggest that the autonomic dysfunction in mdx mice may be independent of decreased myocardial nNOS. These electrocardiographic findings in dystrophin-deficient mice may provide new bases for diagnosing, understanding, and treating DMD patients. |
| Databáze: | OpenAIRE |
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