Novel Therapeutic Intervention for Myocardial infarction in large animal Model

2021 ◽  
Author(s):  
Maria Mercedes
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Therapeutic Intervention ◽  
Large Animal Model ◽  
Large Animal ◽  
Novel Therapeutic

scholarly journals A Nonthoracotomy Myocardial Infarction Model in an Ovine Using Autologous Platelets

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Tyler Spata ◽  
Daniel Bobek ◽  
Bryan A. Whitson ◽  
Sampath Parthasarathy ◽  
Peter J. Mohler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Myocardial Infarct ◽  
Border Zone ◽  
Large Animal Model ◽  
Large Animal ◽  
Ovine Model ◽  
Intravascular Thrombosis ◽  
Serial Serum ◽  
Male Sheep

Objective. There is a paucity of a biological large animal model of myocardial infarction (MI). We hypothesized that, using autologous-aggregated platelets, we could create an ovine model that was reproducible and more closely mimicked the pathophysiology of MI.Methods. Mepacrine stained autologous platelets from male sheep (n=7) were used to create a myocardial infarction via catheter injection into the mid-left anterior descending (LAD) coronary artery. Serial daily serum troponin measurements were taken and tissue harvested on post-embolization day three. Immunofluorescence microscopy was used to detect the mepacrine-stained platelet-induced thrombus, and histology performed to identify three distinct myocardial (infarct, peri-ischemic “border zone,” and remote) zones.Results. Serial serum troponin levels (μg/mL) measured0.0±0.0at baseline and peaked at297.4±58.0on post-embolization day 1, followed by153.0±38.8on day 2 and76.7±19.8on day 3. Staining confirmed distinct myocardial regions of inflammation and fibrosis as well as mepacrine-stained platelets as the cause of intravascular thrombosis.Conclusion. We report a reproducible, unique model of a biological myocardial infarction in a large animal model. This technique can be used to study acute, regional myocardial changes following a thrombotic injury.

In vivo 19F MR inflammation imaging after myocardial infarction in a large animal model at 3 T

2018 ◽  
Vol 32 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Maik Rothe ◽  
Annika Jahn ◽  
Kilian Weiss ◽  
Jong-Hee Hwang ◽  
Julia Szendroedi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Inflammation Imaging

Abstract 114: Allogeneic Cardiosphere-Derived Cells Are Safe and Effective in a Pig Model of Myocardial Infarction

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Rachel R Smith ◽  
Michelle Kreke ◽  
Konstantinos Malliaras ◽  
Hideaki Kanazawa ◽  
Christene A Huang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Safety Concern ◽  
Small Animal ◽  
Immunological Response ◽  
Balloon Occlusion ◽  
Large Animal Model ◽  
Large Animal ◽  
Translational Study ◽  
Post Infusion

Allogeneic cardiosphere-derived cells (CDCs) have proven safe and effective in a small animal model of myocardial infarction (MI), and have been shown to act primarily via paracrine mechanisms to stimulate endogenous regeneration. The present translational study tested allogeneic CDCs in a large animal model (mini-pigs). To establish a robust allogeneic model, all pigs were swine leukocyte antigen (SLA) typed by PCR. A male donor and female recipients with full SLA I, II mismatch were used. Pigs underwent balloon occlusion of the LAD for 2.5 hours, followed by reperfusion. Two weeks later, 12.5 million CDCs (n=8) or vehicle (n=6) were infused. Animals were sacrificed 2 weeks or 2 months post-infusion to assess the cellular (histology using a clinical rejection scale) and humoral (donor-specific antibodies, complement-dependent cytotoxicity) immune responses, as well as cardiac function (left ventriculography, hemodynamics, morphometry). Numerous in-life assessments for safety were performed and CDC engraftment was assessed by FISH for Y chromosome. All immunological assays indicated an undetectable response to CDCs. Cardiac enzymes and systemic inflammation showed no differences between groups. There were no systemic histological findings related to CDCs. CDCs did not permanently engraft, with <0.1% persisting 2 weeks post-infusion and none evident 2 months post. Despite evanescent engraftment, functional benefits were seen following infusion of CDCs. Ejection fraction (EF) and infarct size (IS) were significantly improved in CDC-treated animals compared to vehicle-treated 2 weeks post-infusion (EF: 48.6±2.1% vs 38.2±2.6%, p<0.05; IS: 9±2 vs 14±2%, p<0.05). At 2 months, EF still trended higher in CDC-treated animals (42±5 vs 32±10%, p=0.09), and IS still trended lower (14±4 vs 16±7%, p=0.60). Pressure-volume relationships revealed a trend for enhanced contractility in CDC-treated animals (Emax: 3.2±2.2 vs 1.0±1.1 mmHg/mL, p=0.26). The magnitude of the functional benefits was similar to that seen in a prior pig study using autologous CDCs. Overall, results of the present study demonstrate that allogeneic CDCs are largely equivalent to autologous in terms of efficacy, and elicit no detectable immunological response or safety concern.

Testing of Intra-Myocardial Cell Therapy in a Large Animal Model of Myocardial Infarction

2009 ◽  
Vol 18 ◽  
pp. S190
Author(s):  
Anthony J. White ◽  
Shuo-Tsan Lee ◽  
Satoshi Matsushita ◽  
Eduardo Marbán ◽  
Raj Makkar
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Cell Therapy ◽  
Myocardial Cell ◽  
Large Animal Model ◽  
Large Animal

CHALLENGING VOLTAGE MAPPING FOR SCAR DECHANNELING IN A LARGE ANIMAL MODEL OF MYOCARDIAL INFARCTION

2018 ◽  
Vol 71 (11) ◽  
pp. A304
Author(s):  
Tobias Plenge ◽  
Johannes Terporten ◽  
Alexandra Maul ◽  
Arian Sultan ◽  
Jakob Lueker ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Large Animal Model ◽  
Large Animal ◽  
Voltage Mapping

Abstract 14071: In-vivo Assessment of the Peri-infarcted Region by a Novel Micro-electrode Array System in a Large Animal Model of Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tobias Plenge ◽  
Maria Guschlbauer ◽  
Alexandra Maul ◽  
Marcel Halbach ◽  
Benjamin Krausgrill ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Conduction Velocity ◽  
Electrode Array ◽  
Large Animal Model ◽  
Large Animal ◽  
Impulse Propagation ◽  
Micro Electrode Array ◽  
Infarcted Region

Introduction: Ventricular arrhythmias are life threatening complications in ischemic cardiomyopathy associated with significant mortality. Inhomogeneity in conduction and dispersion of refractoriness are substrates for reentry tachycardias. Micro-electrode array (MEA) systems are currently used to study extracellular field potentials of myocytes in vitro. Hypothesis: Aim of this study was to validate and apply for the first time a novel epicardial MEA 128-channel electrode in a large animal model of myocardial infarction (MI). Methods: We induced MI by percutaneous coil occlusion of the proximal LAD in swine (body weight: 20±1.5 kg, n=6). Epicardial mapping in-vivo was performed by a lateral mini thoracotomy (length 5 cm) with placement of a flexible 128-channel-MEA (32x32 mm, 100 μm electrodes with 2.7 mm distance) on (a) healthy, (b) infarcted and (c) peri-infarcted areas of the left ventricle. Animals were stimulated with predefined pacing protocols. Results: We assed global as well as regional function after MI confirming its efficacy and impact. Application of the MEA - electrode was safe and feasible, showing reproducible results in all animals. Analyzing different ventricular regions in 2D- reconstruction maps we found the inhomogeneity of conduction velocity to be significantly increased creating a characteristic pattern in the peri-infarcted region ( Figure A ). At each electrode the local ECG was registered to calculate differences in activation time. In comparison to recordings prior to the MI the peri-infarct tissue exhibited significant aberrations in spontaneous impulse propagation ( Figure B ) as well as in pacing protocol measurements. Conclusions: We applied and demonstrated the feasibility of in-vivo epicardial MEA - mapping in a swine large animal model of MI. We believe this tool holds great potential for evaluating conduction velocity and impulse propagation for testing regenerative and anti-arrhythmic therapeutic strategies.

scholarly journals Electromechanical wave imaging and electromechanical wave velocity estimation in a large animal model of myocardial infarction

2017 ◽  
Vol 62 (24) ◽  
pp. 9341-9356 ◽  
Author(s):  
Alexandre Costet ◽  
Lea Melki ◽  
Vincent Sayseng ◽  
Nadira Hamid ◽  
Koki Nakanishi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Model ◽  
Wave Velocity ◽  
Velocity Estimation ◽  
Large Animal Model ◽  
Large Animal ◽  
Wave Imaging
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