Dataset Information

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.

SUBMITTER: Veltkamp R

PROVIDER: S-EPMC6438414 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction.

Veltkamp Roland R Uhlmann Stefan S Marinescu Marilena M Sticht Carsten C Finke Daniel D Gretz Norbert N Gröne Herrmann-Josef HJ Katus Hugo A HA Backs Johannes J Lehmann Lorenz H LH

Journal of cachexia, sarcopenia and muscle 20181030 1

<h4>Background</h4>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.<h4>Methods and results</h4>Mice were subjected to filament-induced left middle cerebral artery occlusion for 30 or 60 min or sham surgery and underwent repetitive micro-echoc ...[more]

PMID: 30378296

Similar Datasets

Project description:BackgroundAn increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages.ObjectivesTo assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA).Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting.Selection criteriaWe considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA.Data collection and analysisTwo review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method.Main resultsWe identified no studies that met the inclusion criteria.Authors' conclusionsThere is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.

Project description:ObjectivesThe aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).DesignOur study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).SettingWe derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measuresThe primary outcome was a new stroke, LDL-C goal (LDL-C<1.8mmol/L and LDL-C<1.4mmol/L, respectively) achievement rates, and LLT compliance within 3, 6, and 12 months. The secondary outcomes included major adverse cardiovascular events (MACE) and all caused death at 3 and 12 months.ResultsAmong the 15,166 patients, over 90% of patients received LLT during hospitalization and 2 weeks after discharge; the LLT compliance was 84.5% at 3 months, 75.6% at 6 months, and 64.8% at 12 months. At 12 months, LDL-C goal achievement rate for 1.8mmol/L and 1.4mmol/L was 35.4% and 17.6%, respectively. LLT at discharge was associated with reduced risk of ischemic stroke recurrence (HR=0.69, 95% CI: 0.48-0.99, p=0.04) at 3 months. The rate of LDL-C reduction from baseline to 3-month follow-up was not associated with a reduced risk of stroke recurrence or major adverse cardiovascular events (MACE) at 12 months. Patients with baseline LDL-C ≤1.4mmol/L had a numerically lower risk of stroke, ischemic stroke and MACE at both 3 months and 12 months.ConclusionsThe LDL-C goal achievement rate has increased mildly in the stroke and TIA population in mainland China. Lowered baseline LDL-C level was significantly associated with a decreased short- and long-term risk of ischemic stroke among stroke and TIA patients. LDL-C<1.4mmol/L might be a safe standard for this population.

Project description:Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, all or the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe.

Dataset Information

Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction.

Background

Methods and results

Conclusions

Publications

Experimental ischaemic stroke induces transient cardiac atrophy and dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets