Immune-Response Contributes to Primary Cardiac Dysfunction After Intracerebral Hemorrhage
Li W, Yan T, Li L, Venkat P, Chopp M, Chen Z, Landschoot-Ward J, and Chen J. Stroke 2019; 50.
Background: Cardiac damage may occur after stroke in the absence of primary cardiac diseases. In this study, we investigated whether intracerebral hemorrhage (ICH) induces cardiac dysfunction in the absence of primary cardiac disease, and evaluated the role of the immune-response in mediating post ICH cardiac dysfunction in mice. Methods: Adult male C57BL/6J mice were subjected to ICH by blood injection or sham control without blood injection. To identify whether immunoresponse mediates brain-heart interaction after ICH, splenectomy was performed immediately after ICH. The experimental groups include: 1) sham control; 2) ICH group; 3) ICH+ splenectomy (n=10-16/group). Cardiac function was measured by echocardiography at 7 and 28 days after ICH. Neurological and cognitive functional tests, flow cytometry and immunostaining were performed. Results: Compared to sham control mice, ICH mice exhibit significantly (p<0.05): 1) increased neurological and cognitive deficits, and increased cardiac dysfunction identified by decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and fractional shortening (FS) at 7 and 28 days after ICH. 2) increased cardiomyocyte apoptosis, cardiac hypertrophy and fibrosis at 28 days after ICH; 3) increased inflammatory factor monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-9 expression in the heart and increased inflammatory cell (macrophages:CD45+/CD11b+/F480+ and neutrophil:CD45+/CD11b+/Ly6G+) infiltration into the heart at 7 days post-ICH. Compared to ICH control mice, ICH with splenectomy mice exhibited significantly (p<0.05): 1) improved neurological and cognitive functional outcome as well as attenuated cardiac dysfunction with increased LVEF and LVFS; 2) decreased cardiomyocyte apoptosis, cardiac fibrosis and hypertrophy in the heart; 3) decreased infiltration of immune cells and decreased MCP-1 expression in the heart. Conclusions: ICH not only induces neurological and cognitive functional deficit, but also induces cardiac dysfunction and inflammatory cell infiltration into heart. Immune-response, as evidenced by the effects of splenectomy in conjunction with ICH, may contribute to brain-heart adverse interaction after ICH.