Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction

Abstract

Background Stroke can lead to cardiac dysfunction in patients, but the mechanisms underlying the interaction between the injured brain and the heart are poorly understood. The objective of the study is to investigate the effects of experimental murine stroke on cardiac function and molecular signalling in the heart. Methods and results Mice were subjected to filament‐induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro‐echocardiography. Left ventricular contractility was reduced early (24–72 h) but not late (2 months) after brain ischaemia. Cardiac dysfunction was accompanied by a release of high‐sensitive cardiac troponin (hsTNT (ng/ml): d1: 7.0 ± 1.0 vs. 25.0 ± 3.2*; d3: 7.3 ± 1.1 vs. 52.2 ± 16.7*; d14: 5.7 ± 0.8 vs. 5.2 ± 0.3; sham vs. 60 min. MCAO; mean ± SEM; * p < 0.05); reduced heart weight (heart weight/tibia length ratio: d1: 6.9 ± 0.2 vs. 6.4 ± 0.1*; d3: 6.7 ± 0.2 vs. 5.8 ± 0.1*; d14: 6.7 ± 0.2 vs. 6.4 ± 03; sham vs. 60 min. MCAO; mean ± SEM; * p < 0.05); resulting from cardiomyocyte atrophy (cardiomyocyte size: d1: 12.8% ± 0.002**; d3: 13.5% ± 0.002**; 14d: 6.3% ± 0.003*; 60 min. MCAO vs. sham; mean ± SEM; ** p < 0.01; * p < 0.05), accompanied by increased atrogin‐1 and the E3 ubiquitin ligase murf‐1. Net norepinephrine but not synthesis was increased, suggesting a reduced norepinephrine release or an increase of norepinephrine re‐uptake, resulting in a functional denervation. Transcriptome analysis in cardiac tissue identified the transcription factor peroxisome proliferator‐activated receptor gamma as a potential mediator of stroke‐induced transcriptional dysregulation involved in cardiac atrophy. Conclusions Stroke induces a complex molecular response in the heart muscle with immediate but transient cardiac atrophy and dysfunction.

Cardiac parameters affect prognosis in patients with non-large atherosclerotic infarction

“…MicroRNA also plays an important role in brain–heart interaction (Han et al 2015 ; Min 2009 ). Chen et al ( 2017b ) found in the study that compared with non-stroke animals, stroke mice have significantly lower heart EF, meanwhile, atrogin-1 and E3 ubiquitin ligase murf-1 were elevated, and the transcription factor peroxisome proliferative activated receptor was a potential mediator of transcriptional dysregulation in stroke-related myocardial atrophy (Veltkamp 2019 ). At the same time, stroke significantly increased macrophage infiltration and increased levels of Interleukin-1(IL-1), Interleukin-6(IL-6), Monocyte-chemoattractant protein-1(MCP-1), tumor necrosis factor-β(TGF-β) and macrophage-related inflammatory cytokines in the heart, and induced cardiac fibrosis (Yan 2020 ).…”

Cachexia as a common characteristic in multiple chronic disease

“…Body weight loss after neurological stroke is frequently observed in clinical and experimental settings and associated with adverse clinical outcome . The consequences of ischaemic stroke on myocardium have been investigated in an experimental study by Veltkamp et al ., which showed a transient myocardial dysfunction and atrophy of cardiomyocytes following the brain ischaemia. Further clinical studies investigating cachexia and muscle wasting in patients with stroke are warranted.…”

Cardiomyocyte Injury Following Acute Ischemic Stroke: Protocol for a Prospective Observational Cohort Study (Preprint)

“…Together with the finding that half of the patients with AIS with markedly elevated cTn had no coronary artery disease at all, this implies that alternative mechanisms beyond ACS may play an important role [17]. This is supported by animal research and clinical and neuroimaging studies, suggesting that stroke-associated myocardial injury may originate from structural and/or functional interference within the central autonomic nervous system (CAN) with an overshooting sympathetic response [18][19][20]. On a cellular basis, it is assumed that excessive catecholamine and cortisol levels lead to an increased sarcoplasmic calcium influx with a consecutive hypercontraction of the sarcomeres, electrical instability, and metabolic and oxidative stress.…”