Background: The incidence of cardiovascular diseases is approximately three times higher in patients with neurological diseases than in patients without neurological diseases. Clinical findings have demonstrated that 70% of stroke patients exhibit cardiac dysfunction. Myocardial injury may occur after stroke in the absence of primary cardiac causes. In this study, we tested the hypothesis that age affects brain-heart interaction after cerebral ischemic stroke, and that aging increases cardiac dysfunction after stroke.
Methods: Young adult (2-3 months), middle age (8-9 months) and aged (17-18 months) male C57BL mice were subjected to distal middle cerebral artery occlusion (dMCAo) or sham control (n=10/group). Cardiac hemodynamics and function were measured by transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after surgery. Immunostaining of heart tissues were performed. To elucidate the mechanisms of stroke mediated cardiac dysfunction, heart tissue flow cytometry was employed to measure myocardial inflammation at 4 days after stroke in middle aged mice (n=6/group).
Results: 1) Stroke mice exhibited an age dependent decrease in cardiac function: Stroke in young adult mice induced mild cardiac dysfunction; While the middle age and aged stroke mice exhibited significantly increased cardiac dysfunction compared to age matched sham controls, respectively (p<0.05). Middle age stroke mice exhibit significantly decreased ejection fraction (EF), and increased left ventricular systolic volume (LVVOLs) and LV volume during diastole (LVVOLd); Aged stroke mice exhibited significantly decreased EF and fractional shortening, increased LVVOLs LVVOLd, LV end-diastolic and end-systolic diameter, when compared to age matched sham controls, respectively. 2) Middle age and aged stroke mice exhibited significantly increased myocyte hypertrophy and fibrosis measured by Sirius red collagen staining. 3) Middle aged stroke mice exhibited significantly increased CD45 and CD11bhigh/CD45+ inflammation cell infiltration in the heart compared to middle age sham controls.
Conclusion: Stroke induces cardiac dysfunction. Age affects brain-heart interaction, and age aggravates heart damage after cerebral ischemic stroke.