3 years ago

Stroke-Induced Chronic Systolic Dysfunction Driven by Sympathetic Overactivity

Takahiro Higuchi, Oliver Ritter, Christoph Kleinschnitz, Ulrich Hofmann, Peter U. Heuschmann, Rudolf A. Werner, Michael Bieber, Stefan Frantz, Edit Tanai, Peter Kraft, Kai Schuh
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. While 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/ana.25073

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