Ventricular Arrhythmia after Acute Myocardial Infarction: ‘The Perfect Storm’

Bhar-Amato, Justine; Davies, William; Agarwal, Sharad

doi:10.15420/aer.2017.24.1

Cited by 102 publications

(91 citation statements)

References 70 publications

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“…As there is a close relationship between the infarct size and the incidence of VA [30], the significant reduction of the developed VA in the SRI group could not be attributed to the infarct size because there was no significant difference in the infarction area between the SRI and the URI group, early after the second infarction. The Hematoxylin and Eosin staining of the heart sections 48 h after the second intervention (second LAD ligation in SRI and URI groups, re-thoracotomy in MIC group) shows no infarct area expansion and new inflammatory cell infiltration in the MIC group.…”

Section: Discussionmentioning

confidence: 95%

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

Sadraddin

Gaebel

Skorska

et al. 2019

Cells

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Background: Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance. Methods: Human bone marrow derived CD271 + mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2 −/− γc −/− mouse strain subjected to myocardial "infarction-reinfarction". The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 min with a subsequent second permanent LAD ligation after seven days from the first infarct. Results: This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271 + MSC after the first MI significantly reduced VA induced after the second MI. Conclusions: In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271 + stem cells in vivo. make them very unlikely to produce hazardous action potentials or contribute to arrhythmias [10,11]. However, the availability of a realistic small animal model reflecting the situation in patients is of utmost importance. For testing the rhythmological behavior of human cells, Rag2 −/− γc −/− has been selected. These mice (strain C, 129S4-Rag2 tm1.1Flv Il2rg tm1.1Flv /J) have been derived from a V17 embryonic stem cell line (BALB/c × 129 heterozygote) targeted for the Rag2 and Il2rg genes and lack B, T, and natural killer (NK) cells [12]. They have a deletion of the common cytokine receptor γ chain (γc) gene, and thus reduced numbers of peripheral T and B lymphocytes, and absent natural killer cell (NK) activity. A genetic cross with a recombinase activating gene 2 (RAG2) deficient strain produced mice doubly homozygous for the γc and RAG2 null alleles (Rag2 −/− γc −/− ) with a stable phenotype characterized by the absence of all T lymphocyte, B lymphocyte, and NK cell function [13]. This phenotype makes the completely a lymphoid strain useful for studies on human tissue xenotransplantation [14].As previously shown, stem cell antiarrhythmic effects appear after completion of an approximately one-week engraftment period [4]. The major objective of the present study was to develop a mouse model that enables us to reproduce VA several days after an initial MI. In vivo electrophysiological mouse models are well established: Previously, Berul et al. established an open chest epicardial study of conduction properties with the ability to induce second and third degree heart blocks, but no induction of tachyarrhythmias after programmed stimulation [15]. Hagendorff et al. used a rapid t...

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Section: Discussionmentioning

confidence: 95%

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

Sadraddin

Gaebel

Skorska

et al. 2019

Cells

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“…4d ii). Our data shows that bioprinted scars disrupt electrophysiological synchronization in engineered cardiac microtissues, which mimics conduction blocks that can lead to arrythmias following pathological remodeling post-MI 54 .…”

Section: D Bioprinting High-cell Density Tissue Models Through Direcmentioning

confidence: 72%

3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

Daly

Burdick

2020

Preprint

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Cellular models are needed to study human development and disease in vitro, including the screening of drugs for toxicity and efficacy. However, current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a new bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and for the screening of drugs, particularly where high cell densities and heterogeneity are important.

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“…VTA is a common but fatal complication of AMI. Although there are some electrocardiographic and imaging abnormalities, such as EF<35%, long Q-T interval and R on T wave, may have a close relationship with VTA (14,15). Unfortunately, there is no generally accepted prediction model to identify high-risk patients accompanied with ventricle tachyarrhythmia after acute myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Artificial Neural Network-based Predicting the Risk of Complicating Ventricular Tachyarrhythmia After Acute Myocardial Infarction During Hospitalization

Zheng

Nong

Feng

et al. 2020

Preprint

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An artificial neural network (ANN) model was developed to predict the risks of complicating ventricular tachyarrhythmia (VTA) in patients with acute myocardial infarction (AMI). We enrolled information of 503 patients with 13 risk factors from the affiliated hospital of Guangdong medical university from January 2017 to December 2019. Risk factors were dimensionally reduced and simplified as new variables by principal component analysis (PCA). The cohort were randomly divided into a training set and a testing set at the ratio of 70%:30%. Training set was used to develop a model for the prediction of VTA while testing set was used to evaluate the performance of the model. Three new comprehensive variables by PCA are able to reflect all information of the original data. We determined the prediction model with optimizing parameters by cyclic searching which includes an input layer of three comprehensive variables, a single hidden layer composed of two neurons and a output layer. The area under curve (AUC) is 0.812 in training set and confusion matrix with accuracy 94.60%, sensitivity 63.04%, specificity 99.35%, positive predicative value 93.55%, negative predictive value 94.70%. The model displayed a decreased but medium discrimination with an AUC of 0.688 in the independent testing cohort, confusion matrix with accuracy 87.42%, Sensitivity 39.26%, specificity 98.37%, positive predicative value 84.62%, negative predictive value 87.68%. The research suggests that ANN model could be used to predict the risk of complicating ventricular tachyarrhythmia after acute myocardial infarction while should be further improved.

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Ventricular Arrhythmia after Acute Myocardial Infarction: ‘The Perfect Storm’

Cited by 102 publications

References 70 publications

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model

3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

Artificial Neural Network-based Predicting the Risk of Complicating Ventricular Tachyarrhythmia After Acute Myocardial Infarction During Hospitalization

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