Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses

Abstract

Patients with acute ischemic stroke (AIS) present an increased incidence of systemic inflammatory response syndrome and release of Troponin T coinciding with cardiac dysfunction. The nature of the cardiocirculatory alterations remains obscure as models to investigate systemic interferences of the brain-heart-axis following AIS are sparse. Thus, this study aims to investigate acute cardiocirculatory dysfunction and myocardial injury in mice after reperfused AIS. Ischemic stroke was induced in mice by transient right-sided middle cerebral artery occlusion (tMCAO). Cardiac effects were investigated by electrocardiograms, 3D-echocardiography, magnetic resonance imaging (MRI), invasive conductance catheter measurements, histology, flow-cytometry, and determination of high-sensitive Troponin T (hsTnT). Systemic hemodynamics were recorded and catecholamines and inflammatory markers in circulating blood and myocardial tissue were determined by immuno-assay and flow-cytometry. Twenty-four hours following tMCAO hsTnT was elevated 4-fold compared to controls and predicted long-term survival. In parallel, systolic left ventricular dysfunction occurred with impaired global longitudinal strain, lower blood pressure, reduced stroke volume, and severe bradycardia leading to reduced cardiac output. This was accompanied by a systemic inflammatory response characterized by granulocytosis, lymphopenia, and increased levels of serum-amyloid P and interleukin-6. Within myocardial tissue, MRI relaxometry indicated expansion of extracellular space, most likely due to inflammatory edema and a reduced fluid volume. Accordingly, we found an increased abundance of granulocytes, apoptotic cells, and upregulation of pro-inflammatory cytokines within myocardial tissue following tMCAO. Therefore, reperfused ischemic stroke leads to specific cardiocirculatory alterations that are characterized by acute heart failure with reduced stroke volume, bradycardia, and changes in cardiac tissue and accompanied by systemic and local inflammatory responses.

Post-stroke arrhythmia could be a potential predictor for post-stroke depression

“…Various clinical and experimental studies showed that sympathetic overdrive and reduced parasympathetic activity might be the key mediator between stroke and cardiac events including arrhythmia 25 . Besides, experimental studies showed that stroke-heart syndrome was accompanied by systemic inflammation and suggested that inflammation was involved in the pathogenesis of stroke-heart syndrome 26 . Similarly, autonomic dysfunction and inflammation were also important drivers of depression including post-stroke depression 27 , 28 .…”

Stroke–heart syndrome: current progress and future outlook

“…Animal experiments have demonstrated a fourfold increase in cTn level in mice 24 h after middle cerebral artery occlusion (MCAO), correlating with elevated mortality [72]. High initial and peak cTn levels are associated with poorer neurological outcomes and increased mortality, with dynamic cTn changes doubling in-hospital death risk [35].…”

“…Inflammatory responses and immune regulation significantly impact stroke-cardiac interactions [72,84,85,95]. Ischemic stroke (IS) induces systemic and local cardiac inflammation and causes acute HF with increased circulating cTn levels and bradycardia [72,96,97]. Interleukin (IL)-1 is pivotal in SIHI by enhancing the inflammatory response [5].…”

Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk

“…TMAO, a metabolite derived from gut microbes, also adversely affects cardiomyocytes and coronary endothelial cells ( Peh et al, 2022 ). An animal study illustrated that the number of granulocytes in myocardial tissue increased, and the concentrations of proinflammatory cytokines IL-1β and IL-6 were also nearly doubled in mice after transient middle cerebral artery occlusion (tMCAO), which could lead to cardiac dysfunction and hemodynamic impairment ( Vornholz et al, 2021 ). Hermanns et al found that in middle cerebral artery occlusion (MCAO) mice, the severity of neuroinflammation correlated with cardiac function.…”