Abstract
Abstract P202: Targeting the Cardiac Sympathetic Afferent Reflex in Hypertrophic Cardiomyopathy
Hypertension (Dallas, Tex. 1979), Vol.72(Suppl_1)
09/2018
DOI: 10.1161/hyp.72.suppl_1.P202
Abstract
Sarcomere gene mutations cause hypertrophic cardiomyopathy (HCM). Hallmark features include cardiac hypertrophy, fibrosis, excessive cardiac sympathetic tone, and increased risk of arrhythmias and sudden death. The mechanism(s) of increased sympathetic tone is poorly understood. We hypothesized that cardiac spinal (sympathetic) afferents are sensitized by metabolites (e.g., H+) produced during myocyte energy depletion in HCM, resulting in an enhanced cardiac sympathetic afferent reflex (CSAR). We studied mice with cardiac-specific expression of mutated alpha-tropomyosin (Glu180Gly), an established model of HCM. The CSAR was assessed by measuring mean arterial pressure (MAP) and heart rate (HR) responses to epicardial application of the TRPV1 agonist capsaicin (2.5mM, 2μL) to the left ventricle in anesthetized, ventilated HCM (n=5) and wild-type (WT) littermate control (n=5) mice. Pressor and tachycardic responses to capsaicin were markedly enhanced in HCM mice (Table). Blocking the tonic influence of cardiac afferent activity by epicardial application of the local anesthetic lidocaine (2%) caused small, significant decreases in MAP in both groups of mice; but decreased HR markedly in HCM mice only (n=5) (Table). mRNA expression (qPCR) of acid-sensing ion channel 3 was increased by 2-fold in dorsal root ganglia (T1-T9) of HCM vs. WT mice (n=6 each, P<0.05), suggesting a mechanism for sensitization of cardiac sympathetic afferents in HCM. We conclude that the CSAR is enhanced in HCM mice and speculate that increased activity of cardiac ‘sympathetic’ afferent nerves contributes to increased sympathetic tone, arrhythmias and disease progression in HCM.
Details
- Title: Subtitle
- Abstract P202: Targeting the Cardiac Sympathetic Afferent Reflex in Hypertrophic Cardiomyopathy
- Creators
- Robert A Larson - University of IowaYongjun Lu - University of IowaChristopher J Benson - University of IowaMark W Chapleau - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.72(Suppl_1)
- DOI
- 10.1161/hyp.72.suppl_1.P202
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2018
- Academic Unit
- Cardiovascular Medicine; Molecular Physiology and Biophysics; Neuroscience and Pharmacology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Stead Family Department of Pediatrics; Critical Care
- Record Identifier
- 9984302995302771
Metrics
15 Record Views