Attenuation of Left Ventricular Adverse Remodeling With Epicardial Patching After Myocardial Infarction

Liao, Song-Yan; Siu, Chung‐Wah; Liu, Yuan; Zhang, Yuelin; Chan, Wai-Chi; Wu, Ed X.; Wu, Yin; Nicholls, John M.; Tse, Gary; Benser, Michael E.; Rosenberg, Stuart P.; Park, Euljoon; Lau, Chu‐Pak; Tse, Hung‐Fat

doi:10.1016/j.cardfail.2010.02.007

Cited by 29 publications

(30 citation statements)

References 24 publications

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“…These include cardiac restraint devices, such as epicardial patches and wraps. In the study by Liao et al, 17 localized synthetic patches were sutured to the epicardium over an MI in a pig model. In the study by Dvir et al, 6 bioengineered patches were pre-vascularized via heterotopic transplantation onto the omentum.…”

Section: Discussionmentioning

confidence: 99%

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

et al. 2013

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The material properties of myocardium are an important determinant of global left ventricular function. Myocardial infarction results in a series of maladaptive geometric alterations which lead to increased stress and risk of heart failure. In vivo studies have demonstrated that material injection can mitigate these changes. More importantly, the material properties of these injectates can be tuned to minimize wall thinning and ventricular dilation. The current investigation combines experimental data and finite element modeling to correlate how injectate mechanics and volume influence myocardial wall stress. Experimentally, mechanics were characterized with biaxial testing and injected hydrogel volumes were measured with magnetic resonance imaging. Injection of hyaluronic acid hydrogel increased the stiffness of the myocardium/hydrogel composite region in an anisotropic manner, significantly increasing the modulus in the longitudinal direction compared to control myocardium. Increased stiffness, in combination with increased volume from hydrogel injection, reduced the global average fiber stress by ~14% and the transmural average by ~26% in the simulations. Additionally, stiffening in an anisotropic manner enhanced the influence of hydrogel treatment in decreasing stress. Overall, this work provides insight on how injectable biomaterials can be used to attenuate wall stress and provides tools to further optimize material properties for therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

et al. 2013

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“…Our approach is based in part on successful tissue engineering techniques used to restore LV function in mouse, rat, rabbit, canine, and pig models (16). Human clinical trials with similar strategies are now beginning to appear (17).…”

Section: Discussionmentioning

confidence: 99%

Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cell Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function

Dai

Huang

et al. 2011

Journal of the American College of Cardiology

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Objectives The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. Background Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. Methods In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell–derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis-related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein–positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. Results In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein–positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. Conclusions Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function.

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“…[35] The Penn group later concluded that full cardiac restraint, rather than localized restraint of the infarct region, was required to significantly impact remodeling,[36] but other groups have reported improved remodeling and function with localized reinforcement applied as late as 8 weeks after infarction. [37]…”

Section: Discussionmentioning

confidence: 99%

Model-Based Design of Mechanical Therapies for Myocardial Infarction

Fomovsky

Macadangdang

Ailawadi

et al. 2010

J. of Cardiovasc. Trans. Res.

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The mechanical properties of healing myocardial infarcts are a critical determinant of pump function and the transition to heart failure. Recent reports suggest that modifying infarct mechanical properties can improve function and limit ventricular remodeling. However, little attempt has been made to identify the specific infarct material properties that would optimize left ventricular (LV) function. We utilized a finite-element model of a large anteroapical infarct in a dog heart to explore a wide range of infarct mechanical properties. Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic (ESV) volumes, improved LV contractility, but had little effect on stroke volume. A highly anisotropic infarct, with high longitudinal stiffness but low circumferential stiffness coefficients, produced the best stroke volume by increasing diastolic filling, without affecting contractility or ESV. Simulated infarcts in two different locations displayed different transmural strain patterns. Our results suggest that there is a general trade-off between acutely reducing LV size and acutely improving LV pump function, that isotropically stiffening the infarct is not the only option of potential therapeutic interest, and that customizing therapies for different infarct locations may be important. Our model results should provide guidance for design and development of therapies to improve LV function by modifying infarct mechanical properties.

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Attenuation of Left Ventricular Adverse Remodeling With Epicardial Patching After Myocardial Infarction

Cited by 29 publications

References 24 publications

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

Reduced Collagen Deposition in Infarcted Myocardium Facilitates Induced Pluripotent Stem Cell Engraftment and Angiomyogenesis for Improvement of Left Ventricular Function

Model-Based Design of Mechanical Therapies for Myocardial Infarction

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