Previous studies have demonstrated that ischemic stroke (IS) is associated with changes in autonomic cardiac dynamics, elevated cardiac enzymes and plasma catecholamines. This longitudinal study, (the Stroke-Induced Cardiac Failure in Mice and Men (SICFAIL)), assessed the effect of ischemic stroke on cardiac function in mice and the effect of beta blockers on cardiac function.
METHODSIn an animal model, mice underwent induced IS at either the left or the right middle cerebral artery. Cardiac function was assessed by serial transthoracic echocardiography and hemodynamic measurements for eight weeks post-surgery. Blood was collected to assess levels of brain natruretic protein (BNP), epinephrine, norepinephrine, tumor necrosis factor-alpha (TNF-α), and cortisol levels. In a follow-up, the animals were treated with metoprolol, a selective beta-1 blocker.
RESULTSAfter a focal, right (but not left) hemispheric IS, the mice showed a significant change in LV ejection fraction (P<0.05) and an increase in heart rate (P<0.01). In addition, the IS led to an upregulation of BNP (P<0.01) and TNF-alpha (P<0.05) expression. Eight weeks after surgery, the IS mice had increased levels of plasma norepinephrine, epinephrine and cortisol, as compared with the control and sham surgery mice (P<0.05 and P<0.01). In a follow-up study, as compared to placebo treated controls those treated with metoprolol had a significant decrease in heart rate (P<0.05), end-systolic volume (P<0.05), end-diastolic volume (P<0.001) as well as BNP (P<0.01), TNF-alpha (P<0.05), and MMP-9 gene expression (P<0.05).
CONCLUSIONThis animal study found that right ischemic stroke, leading to the development of chronic systolic dysfunction, driven by increased sympathetic activity, which was suppressed by beta blockade.