Left atrial microvascular endothelial dysfunction, myocardial inflammation and fibrosis after selective insular cortex ischemic stroke

• Published in: International journal of cardiology 2019-10, Vol.292, p.148-155
• Main Authors: Balint, Brittany, Jaremek, Victoria, Thorburn, Victoria, Whitehead, Shawn N., Sposato, Luciano A.
• Format: Article
• Language: English
• Subjects: Arrhythmia; Coronary microvascular endothelial dysfunction; Myocardial fibrosis; Myocardial inflammation; Stroke
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2019.06.004

Insular cortex (IC) ischemic strokes are associated with increased risk of cardiac arrhythmias. We have previously hypothesized that the anatomical substrate for post-stroke neurogenic arrhythmias comprises stroke-induced left atrium (LA) coronary microvascular endothelial dysfunction (CMED), and myocardial inflammatory infiltration (MII) leading to myocardial fibrosis. We investigated whether selectively induced IC ischemic stroke in rats results in histopathological changes in the LA. Insular ischemic stroke was induced in 6-month old male Wistar rats via unilateral stereotaxic injection of endothelin-1 into the left or right IC. The control group consisted of rats injected with saline. We histologically examined the LA 28 days after stroke for CMED, MII, and fibrosis. We performed linear regression analyses to assess correlation between the 3 histopathological outcomes. We compared these findings in the distal LA and the LA-pulmonary vein border (LA-PV border), a region of rich autonomic innervation. Right and left IC stroke led to CMED, MII, and fibrosis in the LA. MII was significantly correlated with CMED and fibrosis. The LA-PV border had significantly greater MII and fibrosis than the distal LA. There were no differences in coronary microvascular and myocardial changes between left and right IC strokes. Left and right insular ischemic strokes resulted in CMED, MII, and fibrosis, the pathological hallmark of arrhythmogenic LA tissue. Since these changes were greater within the LA-PV border than in the distal LA tissue, the role of preganglionic fibers at the ganglionated plexi as part of neurogenic arrhythmogenesis warrants further investigation. •Ischemic stroke induced left atrial endothelial dysfunction, inflammation and fibrosis.•Changes were more severe in the periphery of pulmonary vein ganglionated plexi.•There was no evidence of myocardial necrosis, suggesting non-ischemic mechanisms.•There was no increase of troponin T, B-Natriuretic peptide or left atrial enlargement.•Local dysautonomic and inflammatory mechanisms are possible culprits.