Stroke‐induced chronic systolic dysfunction driven by sympathetic overactivity

• Published in: Annals of neurology 2017-11, Vol.82 (5), p.729-743
• Main Authors: Bieber, Michael, Werner, Rudolf A., Tanai, Edit, Hofmann, Ulrich, Higuchi, Takahiro, Schuh, Kai, Heuschmann, Peter U., Frantz, Stefan, Ritter, Oliver, Kraft, Peter, Kleinschnitz, Christoph
• Format: Article
• Language: English
• Subjects: Adrenergic beta-1 Receptor Antagonists - therapeutic use; Animals; Autonomic nervous system; Beta blockers; Brain; Brain Ischemia - blood; Brain Ischemia - complications; Brain Ischemia - physiopathology; Cardiovascular system; Catecholamines; Cerebral blood flow; Coronary artery disease; Deceleration; Echocardiography; Epinephrine - blood; Health risks; Heart; Heart diseases; Heart failure; Heart Failure - prevention & control; Hemodynamics - drug effects; Hemodynamics - physiology; Hydrocortisone - blood; Infarction, Middle Cerebral Artery; Ischemia; Male; Medical personnel; Metoprolol; Metoprolol - therapeutic use; Mice; Natriuretic Peptide, Brain - blood; Norepinephrine - blood; Occlusion; Pharmacology; Physicians; Risk analysis; Risk factors; Rodents; Signaling; Stroke; Stroke - blood; Stroke - complications; Stroke - physiopathology; Surgery; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology; Ventricle
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.25073

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