Abstract | OBJECTIVE: 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.
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Authors | Michael Bieber, Rudolf A Werner, Edit Tanai, Ulrich Hofmann, Takahiro Higuchi, Kai Schuh, Peter U Heuschmann, Stefan Frantz, Oliver Ritter, Peter Kraft, Christoph Kleinschnitz |
Journal | Annals of neurology
(Ann Neurol)
Vol. 82
Issue 5
Pg. 729-743
(Nov 2017)
ISSN: 1531-8249 [Electronic] United States |
PMID | 29023958
(Publication Type: Journal Article)
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Copyright | © 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. |
Chemical References |
- Adrenergic beta-1 Receptor Antagonists
- Natriuretic Peptide, Brain
- Metoprolol
- Hydrocortisone
- Norepinephrine
- Epinephrine
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Topics |
- Adrenergic beta-1 Receptor Antagonists
(therapeutic use)
- Animals
- Brain Ischemia
(blood, complications, physiopathology)
- Echocardiography
- Epinephrine
(blood)
- Heart Failure
(prevention & control)
- Hemodynamics
(drug effects, physiology)
- Hydrocortisone
(blood)
- Infarction, Middle Cerebral Artery
- Male
- Metoprolol
(therapeutic use)
- Mice
- Natriuretic Peptide, Brain
(blood)
- Norepinephrine
(blood)
- Stroke
(blood, complications, physiopathology)
- Sympathetic Nervous System
(drug effects, physiopathology)
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