Intracerebral Hemorrhage Induces Cardiac Dysfunction in Mice Without Primary Cardiac Disease

Figures

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  Figure 1. ICH induces progressive cardiac contractile functional deficits and cardiac hypertrophy measured by echocardiography. (ICH) in mice induces acute (7 days) and chronic (28 days) cardiac dysfunction. (A) Representative pictures of echocardiography, (B) left ventricular ejection fraction (LVEF), (C) left ventricular fractional shortening (LVFS) dimension at end diastolic and end systolic, (D) inter ventricular septum (IVS) dimension at end diastolic and end systolic, (E) left ventricle internal diameter (LVID) dimension at end diastolic and end systolic, (F) left ventricular volume (LV volume) dimension at end diastolic and end systolic. Bar graphs summarize the results from sham mice, ICH mice at 7 days after ICH and at 28 days after ICH. n = 8/group for echocardiography. Data are presented as mean ± SE; *p < 0.05.

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  Figure 2. ICH increases apoptosis, cardiac fibrosis and cardiomyocyte hypertrophy at 28 days after ICH; ICH does not affect DAP, MAP, and SAP compared to sham control mice. ICH in mice induces cardiac fibrosis and cardiomyocyte hypertrophy as well as apoptosis at 28 days after ICH (A) Terminal deoxynucleotidyl transferase (TUNEL) staining for cardiomyocyte apoptosis and quantitative data, scale bar, 20 μm; (B) Picro Sirius Red (PSR) staining and quantitative data for interstitial collagen fraction (ICF) and cardiomyocyte cross-sectional areas (MCSA) measurement at 28 days after ICH, scale bar, 20 μm. (C–E) (DAP), mean arterial pressure (MAP) and systolic arterial pressure (SAP) measurement at 1, 3, 7 days after ICH. Data are presented as mean ± SE, *p < 0.05 compared with sham control.

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  Figure 3. ICH significantly increases systemic inflammatory factor expression and oxidative stress compared to sham control mice. (A) Western blot assay shows that ICH significantly increases systemic inflammatory factor expression at 7 days after ICH such as (B) intercellular adhesion molecule-1 (ICAM-1), (C) Molecular interleukin-1beta (IL-1β) and (E) Transforming growth factor beta (TGF-β). ICH also significantly increases oxidative stress indicated by (D) NADPH oxidase-2 (NOX-2) expression in serum. Data are presented as mean ± SE, *p < 0.05 compared with sham control.

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  Figure 4. ICH significantly increases cardiac inflammatory factor expression and oxidative stress compared to sham control mice. (A) Western blot assay shows that ICH significantly increases cardiac inflammatory factor expression such as (B) intercellular adhesion molecule-1 (ICAM-1), (C) NOX-2, (D) monocyte chemotactic protein-1(MCP-1), and (E) matrix metalloproteinase-9 (MMP-9) in heart tissue at 7 days after ICH compared to sham control group. Data are presented as mean ± SE, *p < 0.05 compared with sham control.

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  Figure 5. ICH model induces brain hemorrhage and increases inflammatory factor leukocyte and macrophage infiltration into brain at 7 days after ICH compared to sham control mice. (A) Hematoxylin and Eosin (H&E) staining images showing that ICH model in mice induces brain hemorrhage. ICH in mice significantly increases expression of (B) leukocyte (marker CD45, scale bar, 20 μm) and (C) microglia/microphage (marker IBA1, scale bar, 50 μm) in brain tissue at 7 days after ICH compared to sham control mice. ICH in mice significantly increases (D) M1 macrophage indicated by CD86 (scale bar, 20 μm) and (E) M2 macrophage indicated by CD206 (scale bar, 20 μm) in brain compared to sham control mice. Data are presented as mean ± SE, *p < 0.05 compared with sham control.

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  Figure 6. ICH significantly increases cardiac inflammatory cell infiltration compared to sham control mice. ICH increases cardiac inflammatory cells infiltration at 7 days after ICH. (A) CD45 (leukocyte marker) and (B) IBA1 (macrophage marker) immunostaining and quantitative data at 7 days after ICH. ICH in mice significantly increases (C) M1 macrophage indicated by CD86 and (D) M2 macrophage indicated by CD206 in heart compared to sham control mice. (A,B) scale bar, 50 μm; (C,D) scale bar, 20 μm. Data are presented as mean ± SE. *p < 0.05 compared with sham.