Cargando…
Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity
OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is establi...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765487/ https://www.ncbi.nlm.nih.gov/pubmed/29023958 http://dx.doi.org/10.1002/ana.25073 |
_version_ | 1783292241028055040 |
---|---|
author | Bieber, Michael Werner, Rudolf A. Tanai, Edit Hofmann, Ulrich Higuchi, Takahiro Schuh, Kai Heuschmann, Peter U. Frantz, Stefan Ritter, Oliver Kraft, Peter Kleinschnitz, Christoph |
author_facet | Bieber, Michael Werner, Rudolf A. Tanai, Edit Hofmann, Ulrich Higuchi, Takahiro Schuh, Kai Heuschmann, Peter U. Frantz, Stefan Ritter, Oliver Kraft, Peter Kleinschnitz, Christoph |
author_sort | Bieber, Michael |
collection | PubMed |
description | OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function. METHODS: To determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure. RESULTS: Focal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction. INTERPRETATION: Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743 |
format | Online Article Text |
id | pubmed-5765487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57654872018-02-01 Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity Bieber, Michael Werner, Rudolf A. Tanai, Edit Hofmann, Ulrich Higuchi, Takahiro Schuh, Kai Heuschmann, Peter U. Frantz, Stefan Ritter, Oliver Kraft, Peter Kleinschnitz, Christoph Ann Neurol Research Articles OBJECTIVE: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function. METHODS: To determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure. RESULTS: Focal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction. INTERPRETATION: Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743 John Wiley and Sons Inc. 2017-11-06 2017-11 /pmc/articles/PMC5765487/ /pubmed/29023958 http://dx.doi.org/10.1002/ana.25073 Text en © 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Bieber, Michael Werner, Rudolf A. Tanai, Edit Hofmann, Ulrich Higuchi, Takahiro Schuh, Kai Heuschmann, Peter U. Frantz, Stefan Ritter, Oliver Kraft, Peter Kleinschnitz, Christoph Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title | Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title_full | Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title_fullStr | Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title_full_unstemmed | Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title_short | Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
title_sort | stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765487/ https://www.ncbi.nlm.nih.gov/pubmed/29023958 http://dx.doi.org/10.1002/ana.25073 |
work_keys_str_mv | AT biebermichael strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT wernerrudolfa strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT tanaiedit strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT hofmannulrich strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT higuchitakahiro strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT schuhkai strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT heuschmannpeteru strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT frantzstefan strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT ritteroliver strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT kraftpeter strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity AT kleinschnitzchristoph strokeinducedchronicsystolicdysfunctiondrivenbysympatheticoveractivity |