The role of acute stress in arrhythmias associated with remodeled ischemic scars

Natalie Hess (Berlin)1, L. Barth (Berlin)1, N. Hegemann (Berlin)1, M. Morneweg (Berlin)1, W. Kübler (Berlin)2, J. Grune (Berlin)1

1Deutsches Herzzentrum der Charite (DHZC) Klinik für Herz-, Thorax- und Gefäßchirurgie Berlin, Deutschland; 2Deutsches Herzzentrum der Charite (DHZC) Institut für Physiologie Berlin, Deutschland


Background: Ventricular tachycardia frequently occurs after acute myocardial infarction (MI). Months and even years after the acute event, MI patients are at increased arrhythmia risk, which may results in complications such as stroke related to atrial fibrillation or, in the worst case, sudden cardiac death due to ventricular arrhythmia. Why MI patients experience arrhythmias in the long run after the acute event and, more importantly, what triggers these arrhythmias remains unknown. Preliminary data from us revealed that immune cells, particularly neutrophils, play a causal role in arrhythmia development after acute MI through the production of reactive oxygen species. Neutrophils are also known to accumulate in the heart during acute stress. Here, we investigate acute stress and the associated immune cell dynamics as trigger for arrhythmia onset in long-term infarcts.

8-12 weeks old, female C57BL/6J mice were subjected to a surgically-induced small-to-mid-size MI with a range of 5-20% necrotic area using permanent ligation of the left coronary artery. Four weeks post-MI, animals were divided into the following groups: i) mice undergoing restraining for 1 hour, serving as a physical stressor, ii) mice exposed to 0.5 ml trimethylthiazoline (TMT), an equivalent of fox urine, for 3 hours, serving as a psychological stressor, and iii) unstressed control mice. Electrocardiograms were recorded before, during and after stress exposure to monitor arrhythmia burden using a telemetric system. Blood samples to assess immune cell counts were taken immediately after stress exposure using flow cytometry.

Ventricular extrasystoles (VES), ventricular salves, bigeminy and atrioventricular blocks (AV-blocks) were observed in all groups with long-term infarcts. In animals exposed to physical and psychological stress, the number of arrhythmias detected during or after stress was higher than before stress exposure. During and after stress, animals with physical stress showed 20% more VES and salves than before restraining. Mice exposed to psychological stress presented with new onset AV-blocks early during exposure, transitioning to cumulative VES and salves later in TMT exposure compared to the time before exposure. Arrhythmia burden of the control group was stable throughout the time of recording. Flow cytometric analyses revealed, that physical stress elevated neutrophil counts and decreased Ly6Chi monocyte counts in the blood compared to unstressed controls. Interestingly, mice stressed psychologically did not show an increase in neutrophil counts, but lower Ly6Chi monocyte counts compared to restrained and unstressed mice. 

Acute physical and psychological stress increases arrhythmia burden in hearts with ischemic scars. Acute stress causes fundamental changes in circulating immune cell populations like neutrophils and Ly6Chi monocytes. Ongoing experiments will reveal if stress-associated immune cell dynamics are causally related to arrhythmia onset in long-term infarcts. Expected results from this project will inform clinical management of MI patients regarding immune cell dynamics and stress management.
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