Experimental model of myocardial infarction: Histopathology and reperfusion damage revisited

Křen, Leoš; Meluzı́n, Jaroslav; Pavlovský, Zdeněk; Mayer, Jiřı́; Kala, Petr; Groch, Ladislav; Horňáček, Ivan; Raušer, Petr; Vlašín, M.

doi:10.1016/j.prp.2010.03.008

Cited by 9 publications

(10 citation statements)

References 3 publications

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“…Several factors could contribute to the lack of significant differences. Kren et al showed accelerated healing and repair kinetics in young pig models of AMI reperfusion like ours [ 67 ], which would limit the length of the experimental window. In addition, high intragroup variability and a reduced number of animals per group are study limitations, especially in the case of negative results.…”

Section: Discussionmentioning

confidence: 93%

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model

et al. 2016

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BackgroundInsulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model.MethodsPig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry.ResultsIntramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium.ConclusionsThe simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0350-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 93%

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model

et al. 2016

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“…Pigs were premedicated as previously described [7]. In brief, propofol (4 mg/kg, IV; Recofol®, Bayer Schering Pharma) was used as an anaesthetic and, after endotracheal intubation, anaesthesia was maintained by 2% sevoflurane inhalation.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, swine are mostly used because of their high similarity to humans, as they share minimal pre-existing coronary collaterals and have a similar coronary physiology and anatomy [6]. Despite acceleration of early myocardial healing process in swine compared to humans [7], histopathologic changes after MI are common with an earliest myocardial necrosis followed by infiltration of myofibroblast and inflammatory cells (i.e. neutrophils, macrophages, lymphocytes and plasma cells), and necrotic tissue replacement by collagen I and III [8].…”

Section: Introductionmentioning

confidence: 99%

Comparison of two preclinical myocardial infarct models: coronary coil deployment versus surgical ligation

et al. 2014

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BackgroundDespite recent advances, myocardial infarction (MI) remains the leading cause of death worldwide. Pre-clinical animal models that closely mimic human MI are pivotal for a quick translation of research and swine have similarities in anatomy and physiology. Here, we compared coronary surgical ligation versus coil embolization MI models in swine.MethodsFifteen animals were randomly distributed to undergo surgical ligation (n = 7) or coil embolization (n = 8). We evaluated infarct size, scar fibrosis, inflammation, myocardial vascularization, and cardiac function by magnetic resonance imaging (MRI).ResultsThirty-five days after MI, there were no differences between the models in infarct size (P = 0.53), left ventricular (LV) ejection fraction (P = 0.19), LV end systolic volume (P = 0.22), LV end diastolic volume (P = 0.84), and cardiac output (P = 0.89). Histologically, cardiac scars did not differ and the collagen content, collagen type I (I), collagen type III (III), and the I/III ratio were similar in both groups. Inflammation was assessed using specific anti-CD3 and anti-CD25 antibodies. There was similar activation of inflammation throughout the heart after coil embolization (P = 0.78); while, there were more activated lymphocytes in the infarcted myocardium in the surgical occlusion model (P = 0.02). Less myocardial vascularization in the infarction areas compared with the border and remote zones only in coil embolization animals was observed (P = 0.004 and P = 0.014, respectively).ConclusionsOur results support that surgical occlusion and coil embolization MI models generate similar infarct size, cardiac function impairment, and myocardial fibrosis; although, inflammation and myocardial vascularization levels were closer to those found in humans when coil embolization was performed.

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“…2E). Calcium deposits associated with reperfusion injury have been documented by magnetic resonance and computed tomography imaging, as well as demonstrated in experimental models [1,2]. The calcific deposits occur in the more recently damaged myocytes.…”

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confidence: 93%

“…They are granular, representing foci of mitochondrial calcium uptake and deposition of calcium phosphate [3]. Calcium overload in reperfused myocardium is thought by some authors to be deleterious since disturbance of calcium balance activates multiple mechanisms that target cell destruction and significantly interfere with repair processes [1][2][3][4]. Other authors have encompassed the possibility that the calcification process is part of the remodeling process, not necessarily affecting long-term cardiac contractility [5].…”

mentioning

confidence: 99%

Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury

Rios

Mâncio

Rodrigues-Pereira

et al. 2014

Cardiovascular Pathology

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Experimental model of myocardial infarction: Histopathology and reperfusion damage revisited

Cited by 9 publications

References 3 publications

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model

Comparison of two preclinical myocardial infarct models: coronary coil deployment versus surgical ligation

Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury

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