scholarly journals miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy

2019 ◽  
Vol 116 (6) ◽  
pp. 1226-1236 ◽  
Author(s):  
Can Gollmann-Tepeköylü ◽  
Leo Pölzl ◽  
Michael Graber ◽  
Jakob Hirsch ◽  
Felix Nägele ◽  
...  
Keyword(s):  
Shock Wave ◽  
Myocardial Fibrosis ◽  
Myocardial Ischaemia ◽  
Heart Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Shock Wave Therapy ◽  
Ventricular Ejection Fraction ◽  
Ischaemic Myocardium

Abstract Aims As many current approaches for heart regeneration exert unfavourable side effects, the induction of endogenous repair mechanisms in ischaemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischaemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischaemia. Methods and results Mechanical stimulation of ischaemic muscle via SWT caused extracellular vesicle (EV) release from endothelial cells both in vitro and in vivo. Characterization of EVs via electron microscopy, nanoparticle tracking analysis and flow cytometry revealed specific exosome morphology and size with the presence of exosome markers CD9, CD81, and CD63. Exosomes exhibited angiogenic properties activating protein kinase b (Akt) and extracellular-signal regulated kinase (ERK) resulting in enhanced endothelial tube formation and proliferation. A miRNA array and transcriptome analysis via next-generation sequencing were performed to specify exosome content. miR-19a-3p was identified as responsible cargo, antimir-19a-3p antagonized angiogenic exosome effects. Exosomes and target miRNA were injected intramyocardially in mice after left anterior descending artery ligation. Exosomes resulted in improved vascularization, decreased myocardial fibrosis, and increased left ventricular ejection fraction as shown by transthoracic echocardiography. Conclusion The mechanical stimulus of SWT causes release of angiogenic exosomes. miR-19a-3p is the vesicular cargo responsible for the observed effects. Released exosomes induce angiogenesis, decrease myocardial fibrosis, and improve left ventricular function after myocardial ischaemia. Exosome release via SWT could develop an innovative approach for the regeneration of ischaemic myocardium.

scholarly journals 4D cardiac magnetic resonance imaging, 4D and 2D transthoracic echocardiography: a comparison of in-vivo assessment of ventricular function in rats

2018 ◽  
Vol 53 (2) ◽  
pp. 169-179
Author(s):  
Hedwig Stegmann ◽  
Tobias Bäuerle ◽  
Katharina Kienle ◽  
Sven Dittrich ◽  
Muhannad Alkassar
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ventricular Function ◽  
Heart Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Technical Effort ◽  
In Vivo Assessment

Preclinical cardiovascular research is the foundation of our understanding and broad knowledge of heart function and cardiovascular disease. Reliable cardiac imaging modalities are the basis for applicable results. Four-dimensional cardiac magnetic resonance (4D CMR) has been set as the gold standard for in-vivo assessment of ventricular function in rodents. However, technical improvements in echocardiography now allow us to image the whole heart, which makes four-dimensional echocardiography (4DE) a possible alternative to 4D CMR. To date, no study has systematically assessed 4DE in comparison with 4D CMR in rats. In total we studied 26 juvenile Sprague-Dawley rats (Crl: CD (SD) IGS). Twenty rats underwent echocardiographic imaging (2D and 4D) and 4D CMR. Five of those rats underwent a ligation of the superior and inferior vena cava to reduce the cardiac inflow as a disease model. Six additional rats were used to assess reproducibility of echocardiography and underwent three echocardiographic examinations. 4D CMR was performed on a 7T scanner; 2D and 4D echocardiography was conducted using a 40 MHz transducer. Correlation between 4D CMR, 4DE and 2DE for left-ventricular ejection fraction (LVEF) was assessed. An excellent correlation was observed between 4DE and 4D CMR ( r = 0.95, p < 0.001). Correlation of 2DE and 4D CMR was weak ( r = 0.57, p < 0.01). 4DE provides results that are equally precise as 4D CMR and highly reproducible with less technical effort than 4D CMR.

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Shao-Ling Yang ◽  
Ke-Qiang Tang ◽  
Jun-Jia Tao ◽  
Ai-Hong Wan ◽  
Yan-Duan Lin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Rabbit Model ◽  
Physiological Saline ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ventricular Ejection Fraction ◽  
Cluster Of Differentiation

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

Abstract 177: Ticagrelor, but not Clopidogrel, Protects the Heart Against Reperfusion Injury and Improves Remodeling After Myocardial Infarction

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yumei Ye ◽  
Jose R Perez-Polo ◽  
Manjyot K Nanhwan ◽  
Sven Nylander ◽  
Yochai Birnbaum
Keyword(s):  
Myocardial Infarction ◽  
Platelet Aggregation ◽  
Reperfusion Injury ◽  
Heart Function ◽  
Oral Treatment ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Coronary Artery Ligation ◽  
Ventricular Ejection Fraction

Background: Clopidogrel (C) and Ticagrelor (T) are P2Y12 ADP receptor antagonists. In addition, ticagrelor inhibits adenosine cell uptake. In PLATO trial T reduced the incidence of the primary composite endpoint myocardial infarction, stroke or cardiovascular death over C in patients with acute coronary syndromes. Previous data show that 7d pretreatment with T limits infarct size (IS) in rats. We compared the effects of C and T, administered just before reperfusion on IS. We also assessed the effect of T and C, administered just before reperfusion and/or 6w oral treatment on cardiac remodeling. Methods: Rats underwent 30min coronary artery ligation. 1) At 25min of ischemia rats received intraperitoneal (IP) vehicle, T (10 or 30mg/kg), or C (12.5mg/kg). Area at risk (AR) was assessed by blue dye and IS by TTC staining 24h after reperfusion. 2) Rats received vehicle without (sham) or with (control) coronary ischemia, T (30mg/kg) IP (TIP), T (300mg/kg/d) oral for 6w, started a day after reperfusion (TPO), TIP+PO (TIPPO), or C (12.5mg/kg IP +62.5mg/kg/d PO for 6w). LV dimensions and function was assessed by echo at 6w. Results: 1) AR was comparable among groups. IS was 45.3±1.7% of the AR in the control group. T10 (31.5±1.8%; p=0.001) and T30 (21.4±2.6% p<0.001) significantly reduced IS, whereas C (42.4±2.6%) had no effect. Platelet aggregation in the controls was 64.7±1.3% and was comparable in T30 (24.9±1.8%) and C (23.2±1.8%) at 2h post reperfusion. T30 increased Akt, eNOS and ER1/2 phosphorylation 4h after reperfusion, whereas C had no effect. 2) Platelet aggregation at 1w oral treatment was 59.7±3.2% in the control group and was comparable in TIPPO (18.1±1.3%) and C (17.4±0.7%). Left ventricular ejection fraction was 77.6±0.9%*, 44.8±3.5%, 69.5±1.6%*, 69.2±1.0%*, 76.3±1.2%*, and 37.4±3.7% in the sham, vehicle, TIP, TPO, TIPPO and C treated group, respectively (*p<0.001 vs. vehicle). Left ventricular diameters at diastole and systole showed the same pattern. Conclusions: T, but not C, administered just before reperfusion protects against reperfusion injury. Oral T (in combination or not with acute treatment just before reperfusion) treatment for 6w improves heart function. C, despite achieving similar degree of platelet inhibition had no effect on remodeling.

Electrophysiologic properties and ventricular fibrillation in normal and myopathic hearts

1999 ◽  
Vol 77 (7) ◽  
pp. 510-519 ◽  
Author(s):  
Katherine M Kavanagh ◽  
Patricia A Guerrero ◽  
Bodh I Jugdutt ◽  
Francis X Witkowski ◽  
Jeffrey E Saffitz
Keyword(s):  
Ventricular Fibrillation ◽  
Myocardial Dysfunction ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Functional Abnormality ◽  
Ventricular Ejection Fraction ◽  
Anisotropic Properties

This study tests the hypothesis that moderate myocardial dysfunction is associated with altered myocardial anisotropic properties and structurally altered ventricular fibrillation (VF). Mongrel dogs were randomized to either a control group or a group that was rapidly paced at 250 beats/min until the left ventricular ejection fraction was [Formula: see text] 40%. Changes in anisotropic properties and the electrical characteristics of VF associated with the development of moderate myocardial dysfunction were assessed by microminiature epicardial mapping studies. In vivo conduction, refractory periods, and repolarization times were prolonged in both longitudinal and transverse directions in myopathic animals versus controls. VF was different in myopathic versus control animals. There were significantly more conducted deflections during VF in normal hearts compared with myopathic hearts. Propagated deflection-to-deflection intervals during VF were significantly longer in myopathic hearts compared with controls (125.5 ± 49.06 versus 103.4 ± 32.9 ms, p = 0.009). There were no abnormalities in cell size, cell shape, or the number of intercellular gap junctions and there was no detectable change in the expression of the gap junction proteins Cx43 and Cx45. Moderate myocardial dysfunction is associated with significant electrophysiological abnormalities in the absence of changes in myocardial cell morphology or intercellular connections, suggesting a functional abnormality in cell-to-cell communication.Key words: cardiomyopathy, anisotropy, fibrillation, defibrillation.

Abstract 165: The 18 kDa FGF-2 Prevents the Doxorubicin-induced Cardiac Damage and Amp-activated Kinase Activation, in vitro and in vivo

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Navid Koleini ◽  
Jon Jon Santiago ◽  
Barbara E Nickel ◽  
Robert Fandrich ◽  
Davinder S Jassal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cell Death ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Wild Type ◽  
Rat Cardiomyocytes ◽  
Ventricular Ejection Fraction ◽  
Compound C

Introduction: Protection of the heart from chemotherapeutic (Doxorubicin, DOX) drug-induced toxicity is a desirable goal, to limit side effects of cancer treatments. DOX toxicity has been linked to the activation (phosphorylation) of the AMP-activated kinase, AMPK. The 18 kDa low molecular weight isoform of fibroblast growth factor 2 (Lo-FGF-2) is a known cardioprotective and cytoprotective agent. In this study we have tested the ability of Lo-FGF-2 to protect from DOX-induced damage in rat cardiomyocytes in vitro, and in transgenic mouse models in vivo, in relation to AMPK activation. Methods: Rat neonatal cardiomyocytes in culture were exposed to DOX (0.5 μM) in the presence or absence of pre-treatment Lo-FGF-2 (10 ng/ml). Compound C was used to block phosphorylation (activity) of AMPK. Levels of cell viability/death (using Calcein-AM/Propidium iodide assay), phospho -and total AMPK, and apoptotic markers such as active caspase 3 were analyzed. In addition, transgenic mice expressing only Lo-FGF2, and wild type mice, expressing both high molecular weight (Hi-FGF2) as well as Lo-FGF2 were subjected to DOX injection (20 mg/kg, intraperitoneal); echocardiography was used to examine cardiac function at baseline and at 10 days post-DOX. Results: DOX-induced cell death of cardiomyocytes in culture was maximal at 24 hours post-DOX coinciding with significantly increased in activated (phosphorylated) AMPK. Compound C attenuated DOX-induced cardiomyocyte loss. Pre-incubation with Lo-FGF-2 decreased DOX induced cell death, and also attenuated the phosphorylation of AMPK post-DOX. Relative levels of phospho-AMPK were lower in the hearts of Lo-FGF2-expressing male mice compared to wild type. DOX-induced loss of contractile function (left ventricular ejection fraction and endocardial velocity) was negligible in Lo-FGF2-expressing mice but significant in wild type mice. Conclusion: Lo-FGF-2 protects the heart from DOX-induced damage in vitro and in vivo, by a mechanism likely involving an attenuation of AMPK activity.

Left bundle branch pacing improved heart function in a 10-year-old child after a 3-month follow-up

EP Europace ◽  
2020 ◽  
Vol 22 (8) ◽  
pp. 1234-1239
Author(s):  
Wei Ji ◽  
Xueying Chen ◽  
Jie Shen ◽  
Diqi Zhu ◽  
Yiwei Chen ◽  
...  
Keyword(s):  
Heart Function ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Bundle Branch Block ◽  
Ventricular Ejection Fraction ◽  
Intracardiac Electrogram ◽  
Ventricular Activation ◽  
Pacing Lead

Abstract Aims As a physiological pacing strategy, left bundle branch pacing (LBBP) were used to correct left bundle branch block (LBBB), however, there is no relevant report in children. We aimed to evaluate the feasibility of LBBP in children. Methods and results Left bundle branch pacing was performed in a 10-year-old girl with a second-degree atrioventricular and LBBB. Under the guide of fluoroscopy, the pacing lead was deeply screwed into the interventricular septum to gain right bundle branch block (RBBB) pattern of paced QRS. Selective LBBP was achieved with a typical RBBB pattern of paced morphology and a discrete component between stimulus and ventricular activation in intracardiac electrogram and reached the standard of the stimulus to left ventricular activation time of 56 ms. At a 3-month follow-up, the LBBP acquired the reduction of left ventricular size and enhancement of left ventricular ejection fraction. Conclusion The application of LBBP in a child was first achieved with inspiring preliminary results. The LBBP can be carried out in children by cautiousness under the premise of strict grasp of indications.

scholarly journals A model based on clinical parameters to identify myocardial late gadolinium enhancement by magnetic resonance in patients with aortic stenosis: An observational study

2020 ◽  
Vol 9 ◽  
pp. 204800402092240
Author(s):  
Mariya Kuk ◽  
Simon Newsome ◽  
Francisco Alpendurada ◽  
Marc Dweck ◽  
Dudley J Pennell ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Aortic Stenosis ◽  
Risk Stratification ◽  
Myocardial Fibrosis ◽  
Surgical Intervention ◽  
Severe Aortic Stenosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Study Patient ◽  
Ventricular Ejection Fraction

Objective With increasing age, the prevalence of aortic stenosis grows exponentially, increasing left heart pressures and potentially leading to myocardial hypertrophy, myocardial fibrosis and adverse outcomes. To identify patients who are at greatest risk, an outpatient model for risk stratification would be of value to better direct patient imaging, frequency of monitoring and expeditious management of aortic stenosis with possible earlier surgical intervention. In this study, a relatively simple model is proposed to identify myocardial fibrosis in patients with a diagnosis of moderate or severe aortic stenosis. Design Patients with moderate to severe aortic stenosis were enrolled into the study; patient characteristics, blood work, medications as well as transthoracic echocardiography and cardiovascular magnetic resonance were used to determine potential identifiers of myocardial fibrosis. Setting The Royal Brompton Hospital, London, UK Participants One hundred and thirteen patients in derivation cohort and 26 patients in validation cohort. Main outcome measures Identification of myocardial fibrosis. Results Three blood biomarkers (serum platelets, serum urea, N-terminal pro-B-type natriuretic peptide) and left ventricular ejection fraction were shown to be capable of identifying myocardial fibrosis. The model was validated in a separate cohort of 26 patients. Conclusions Although further external validation of the model is necessary prior to its use in clinical practice, the proposed clinical model may direct patient care with respect to earlier magnetic resonance imagining, frequency of monitoring and may help in risk stratification for surgical intervention for myocardial fibrosis in patients with aortic stenosis.

scholarly journals Management of perioperative myocardial ischaemia after isolated coronary artery bypass graft surgery

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001027 ◽  
Author(s):  
Davorin Sef ◽  
Janko Szavits-Nossan ◽  
Mladen Predrijevac ◽  
Rajna Golubic ◽  
Tomislav Sipic ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Angiography ◽  
Coronary Artery Bypass ◽  
Myocardial Ischaemia ◽  
Graft Failure ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

ObjectivesUpdated knowledge about perioperative myocardial ischaemia (MI) after coronary artery bypass grafting (CABG) and treatment of acute graft failure is needed. We analysed main factors associated with perioperative MI and effects of immediate coronary angiography-based treatment strategy on patient outcome.MethodsAmong 1119 consecutive patients with coronary artery disease who underwent isolated CABG between January 2011 and December 2015, 43 (3.8%) patients underwent urgent coronary angiography due to suspected perioperative MI. All the data were prospectively collected and retrospectively analysed. The primary endpoint was 30-day mortality; postoperative left ventricular ejection fraction) and major adverse cardiac events were secondary endpoints.ResultsOverall, 30-day mortality in patients with CABG was 1.4% while in patients who developed perioperative MI was 9% (4 patients). Angiographic findings included incorrect graft anastomosis, graft spasm, dissection, acute coronary artery thrombotic occlusion and ischaemia due to incomplete revascularisation. Emergency reoperation (Redo) was performed in 14 (32%), acute percutaneous coronary intervention (PCI) in 15 (36%) and conservative treatment (Non-op) in 14 patients. Demographic and preoperative clinical characteristics between the groups were comparable. Postoperative LVEF was significantly reduced in the Redo group (45% post-op vs 53% pre-op) and did not change in groups PCI (56% post-op vs 57% pre-op) and Non-op (58% post-op vs 57% pre-op).ConclusionsUrgent angiography allows identification of the various underlying causes of perioperative MI and urgent treatment when this is needed. Urgent PCI may be associated with improved clinical outcome in patients with early graft failure.

scholarly journals Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial

2020 ◽  
Vol 71 (702) ◽  
pp. e62-e70
Author(s):  
Yuzhong Wu ◽  
Wengen Zhu ◽  
Xin He ◽  
Ruicong Xue ◽  
Weihao Liang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Retrospective Analysis ◽  
Heart Function ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

BackgroundPolypharmacy is common in heart failure (HF), whereas its effect on adverse outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear.AimTo evaluate the prevalence, prognostic impacts, and predictors of polypharmacy in HFpEF patients.Design and settingA retrospective analysis performed on patients in the Americas region (including the US, Canada, Argentina, and Brazil) with symptomatic HF and a left ventricular ejection fraction ≥45% in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, an international, randomised, double-blind, placebo-controlled study conducted during 2006–2013 in six countries.MethodPatients were categorised into four groups: controls (<5 medications), polypharmacy (5–9 medications), hyperpolypharmacy, (10–14 medications), and super hyperpolypharmacy (≥15 medications). The outcomes and predictors in all groups were assessed.ResultsOf 1761 participants, the median age was 72 years; 37.5% were polypharmacy, 35.9% were hyperpolypharmacy, and 19.6% were super hyperpolypharmacy, leaving 7.0% having a low medication burden. In multivariable regression models, three experimental groups with a high medication burden were all associated with a reduction in all-cause death, but increased risks of HF hospitalisation and all-cause hospitalisation. Furthermore, several comorbidities (dyslipidemia, thyroid diseases, diabetes mellitus, and chronic obstructive pulmonary disease), a history of angina pectoris, diastolic blood pressure <80 mmHg, and worse heart function (the New York Heart Association functional classification level III and IV) at baseline were independently associated with a high medication burden among patients with HFpEF.ConclusionA high prevalence of high medication burden at baseline was reported in patients with HFpEF. The high medication burden might increase the risk of hospital readmission, but not the mortality.

Pharmacological Management of a Heart Failure Patient with Severe Obesity

Cardiology ◽  
2017 ◽  
Vol 138 (Suppl. 1) ◽  
pp. 11-12 ◽  
Author(s):  
Gerardo Riccio
Keyword(s):  
Heart Failure ◽  
Severe Obesity ◽  
Heart Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Pharmacological Management ◽  
Ventricular Ejection Fraction ◽  
Present Case Report ◽  
Patients With Heart Failure

Obesity is one of the commonest comorbidities in patients with heart failure, and it is associated with increased mortality risk. However, obese patients are often underrepresented in clinical trials and therefore evidence on their management remains scant. In order to expand knowledge on the management of these patients, anecdotal reports may be considered. In the present case report, we discuss the successful management of an obese patient who received sacubitril/valsartan therapy. This treatment was initiated after a 12-month period of losartan therapy, which did not provide any benefit in terms of heart function. Importantly, during this period the patient required frequent hospitalizations, with a marked decrease in quality of life. After the switch to sacubitril/valsartan, a 10% increase in left ventricular ejection fraction was observed (from 30 to 40%) over a 12-month period. Moreover, no hospitalizations were required, and the patient was able to carry on at least some of his daily activities.

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