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

Background 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. Methods 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. Results 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. Conclusions 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.