Systemische Wechselbeziehungen zwischen dem ischämischen Schlaganfall und dem Herzen im Mausmodell

Systemic interactions between the ischemic brain and the heart Objectives: To implement a murine model of reperfused acute ischemic stroke (AIS) to study local cardiac and circulatory adaptations Background: Cardiac prognosis in patients with AIS is impaired. Frequent coincidental findings after AIS are systemic inflammation and release of high sensitive Troponin T (hsTnT) with cardiac dysfunction. The nature of cardiac dysfunction and potential therapeutic targets are not known. Standardized models to investigate systemic interferences of the brain-heart-axis and the underlying mechanisms of AIS induced cardiac dysfunction are missing. Methods: Ischemic stroke was induced in 109 C57BL/6J mice by transient right-sided middle cerebral artery occlusion (tMCAO). Cardiac effects were investigated by electrocardiograms, 3D echocardiography, magnetic resonance imaging (MRI), invasive conductance catheter measurements, histology, flow cytometry and determination of plasma hsTnT. Systemic hemodynamics were assessed by conductance catheter measurements. Circulating catecholamines were determined by HPLC and immune-assays. Inflammatory markers were analyzed by flow cytometry. Results: Following tMCAO hsTnT levels were elevated 4-fold compared to sham-operated controls. tMCAO caused a systolic left ventricular dysfunction with significantly reduced stroke volume and impaired global longitudinal strain. Concomitantly reduced cardiac output, impaired ventricular pressure development, and lower mean arterial pressure were observed. Paradoxically, we observed a severe bradycardia. This was accompanied by a systemic inflammatory response characterized by granulocytosis, lymphopenia, increased levels of serum-amyloid A, and interleukin-6. Within myocardial tissue, we noted altered expansion of extracellular space as evidenced by MRI relaxometry, and in parallel number of granulocytes, apoptotic cells, and expression of pro-inflammatory cytokines were elevated. Conclusion: The brain-heart-axis frequently induces specific patterns of cardiac and circulatory adaption to AIS. Acute myocardial infarction does not contribute to this interaction. But an acute myocardial injury with systolic dysfunction and reduced cardiac output occurs, which is accompanied by altered myocardial tissue characteristics associated with a systemic and local myocardial inflammatory response.