scholarly journals Comparative Analysis of Methods to Induce Myocardial Infarction in a Closed-Chest Rabbit Model

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Marc-Antoine Isorni ◽  
Amaury Casanova ◽  
Julie Piquet ◽  
Valérie Bellamy ◽  
Charly Pignon ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Models ◽  
Rabbit Model ◽  
Left Ventricular ◽  
Balloon Occlusion ◽  
Gelatin Sponge ◽  
Large Animal ◽  
Alcohol Injection ◽  
Closed Chest ◽  
Large Animal Models

Objective.To develop a rabbit model of closed-chest catheter-induced myocardial infarction.Background.Limitations of rodent and large animal models justify the search for clinically relevant alternatives.Methods.Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (n=4), interlocking coils (n=4), thrombogenic gelatin sponge (n=4), balloon occlusion (n=4), and alcohol injection (n=8). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction.Results.The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically.Conclusions.By following a stepwise approach, a minimally invasive, effective, and reproducible rabbit model of catheter-induced myocardial infarction has been developed which addresses the limitations of rodent experiments while avoiding the logistical and cost issues associated with large animal models.

scholarly journals Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models

2015 ◽  
Vol 109 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Gerardus P. J. van Hout ◽  
Sanne J. Jansen of Lorkeers ◽  
Kimberly E. Wever ◽  
Emily S. Sena ◽  
Lisanne H. J. A. Kouwenberg ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Animal Models ◽  
Meta Analysis ◽  
Large Animal ◽  
Large Animal Models ◽  
Anti Inflammatory

scholarly journals Reperfused hemorrhagic myocardial infarction in rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243207
Author(s):  
Anand R. Nair ◽  
Eric A. Johnson ◽  
Hsin-Jung Yang ◽  
Ivan Cokic ◽  
Joseph Francis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Major Adverse Cardiovascular Events ◽  
Large Animal ◽  
Ischemic Time ◽  
Rat Models ◽  
Large Animal Models ◽  
Gene And Protein Expression

Background Intramyocardial hemorrhage following reperfusion is strongly associated with major adverse cardiovascular events in myocardial infarction (MI) patients; yet the mechanisms contributing to these outcomes are not well understood. Large animal models have been used to investigate intramyocardial hemorrhage, but they are exorbitantly expensive and difficult to use for mechanistic studies. In contrast, rat models are widely used to investigate mechanistic aspects of cardiovascular physiology, but a rat model that consistently recapitulates the characteristics of an hemorrhagic MI does not exist. To bridge this gap, we investigated the physiological conditions of MI that would create intramyocardial hemorrhage in rats so that a reliable model of hemorrhagic MI would become available for basic research. Methods & results Sprague-Dawley rats underwent either a 90-minute (90-min) ischemia and then reperfusion (I/R) (n = 22) or 30-minute (30-min) I/R (n = 18) of the left anterior descending coronary artery. Sham rats (n = 12) were used as controls. 90-min I/R consistently yielded hemorrhagic MI, while 30-min I/R consistently yielded non-hemorrhagic MI. Twenty-four hours post-reperfusion, ex-vivo late-gadolinium-enhancement (LGE) and T2* cardiac MRI performed on excised hearts from 90-min I/R rats revealed colocalization of iron deposits within the scarred tissue; however, in 30-min I/R rats scar was evident on LGE but no evidence of iron was found on T2* CMR. Histological studies verified tissue damage (H&E) detected on LGE and the presence of iron (Perl’s stain) observed on T2*-CMR. At week 4 post-reperfusion, gene and protein expression of proinflammatory markers (TNF-α, IL-1β and MMP-9) were increased in the 90-min I/R group when compared to 30-min I/R groups. Further, transmission electron microscopy performed on 90-min I/R myocardium that were positive for iron on T2* CMR and Perl’s stain showed accumulation of granular iron particles within the phagosomes. Conclusion Ischemic time prior to reperfusion is a critical factor in determining whether a MI is hemorrhagic or non-hemorrhagic in rats. Specifically, a period of 90-min of ischemia prior to reperfusion can produce rat models of hemorrhagic MI, while 30-minutes of ischemia prior to reperfusion can ensure that the MIs are non-hemorrhagic. Hemorrhagic MIs in rats result in marked increase in iron deposition, proinflammatory burden and adverse left—ventricular remodeling compared to rats with non-hemorrhagic MIs.

scholarly journals iPSC Therapy for Myocardial Infarction in Large Animal Models: Land of Hope and Dreams

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1836
Author(s):  
Daina Martínez-Falguera ◽  
Oriol Iborra-Egea ◽  
Carolina Gálvez-Montón
Keyword(s):  
Myocardial Infarction ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Large Animal ◽  
Technical Application ◽  
In Vivo Models ◽  
Large Animal Models ◽  
Induced Pluripotent

Myocardial infarction is the main driver of heart failure due to ischemia and subsequent cell death, and cell-based strategies have emerged as promising therapeutic methods to replace dead tissue in cardiovascular diseases. Research in this field has been dramatically advanced by the development of laboratory-induced pluripotent stem cells (iPSCs) that harbor the capability to become any cell type. Like other experimental strategies, stem cell therapy must meet multiple requirements before reaching the clinical trial phase, and in vivo models are indispensable for ensuring the safety of such novel therapies. Specifically, translational studies in large animal models are necessary to fully evaluate the therapeutic potential of this approach; to empirically determine the optimal combination of cell types, supplementary factors, and delivery methods to maximize efficacy; and to stringently assess safety. In the present review, we summarize the main strategies employed to generate iPSCs and differentiate them into cardiomyocytes in large animal species; the most critical differences between using small versus large animal models for cardiovascular studies; and the strategies that have been pursued regarding implanted cells’ stage of differentiation, origin, and technical application.

scholarly journals Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat

2010 ◽  
Vol 298 (1) ◽  
pp. H221-H228 ◽  
Author(s):  
Gregory M. Fomovsky ◽  
Jeffrey W. Holmes
Keyword(s):  
Myocardial Infarction ◽  
Mechanical Properties ◽  
Ventricular Function ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Collagen Content ◽  
Lv Function ◽  
Large Animal ◽  
Large Animal Models

The mechanical properties of the healing scar are an important determinant of heart function following myocardial infarction. Yet the relationship between scar structure, scar mechanics, and ventricular function remains poorly understood, in part because no published study has tracked all of these factors simultaneously in any animal model. We therefore studied the temporal evolution of scar structure, scar mechanics, and left ventricular (LV) function in large anterior myocardial infarcts in rats. At 1, 2, 3, and 6 wk after left anterior descending coronary ligation, we examined LV function using sonomicrometry, infarct mechanical properties using biaxial mechanical testing, infarct structure using polarized light microscopy, and scar collagen content and cross-linking using biochemical assays. Healing infarcts in the rat were structurally and mechanically isotropic at all time points. Collagen content increased with time and was the primary determinant of scar mechanical properties. The presence of healing infarcts influenced systolic LV function through a rightward shift of the end-systolic pressure-volume relationship (ESPVR) that depended on infarct size, infarct collagen content, and LV dilation. We conclude that in sharp contrast to previous reports in large animal models, healing infarcts are structurally and mechanically isotropic in the standard rat model of myocardial infarction. On the basis of the regional strain patterns we observed in healing rat infarcts in this study and in healing pig infarcts in previous studies, we hypothesize that the local pattern of stretching determines collagen alignment in healing myocardial infarct scars.

Characteristics and Unmet Clinical Needs Related to Hepatocellular Carcinoma

2017 ◽  
Vol 01 (02) ◽  
pp. 074-082
Author(s):  
Jordan Newson ◽  
Nickolas Kinachtchouk ◽  
Kyle Schachtschneider ◽  
Regina Schwind ◽  
Lawrence Schook
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Models ◽  
Biomedical Research ◽  
Human Disease ◽  
Rabbit Model ◽  
In Vitro Study ◽  
Large Animal ◽  
Curative Therapy ◽  
Large Animal Models

AbstractAdvances in biomedical research require animal models that accurately recapitulate human disease. Without such models, progress against human diseases such as cancer is significantly hindered. Here, we present the current landscape on available and emerging hepatocellular carcinoma (HCC) animal models. HCC is the second leading cause of cancer death worldwide, with an annual death toll exceeding 745,000. Stunningly, only 15% of HCC patients are candidates for curative therapy, leading 85% of patients to seek palliative therapeutic options. The VX2 rabbit model is considered the most relevant and widely used HCC model; however, more reliable HCC models are critically needed. In general, animal models for biomedical research should (1) mimic the human disease on a molecular basis, (2) derive from a relevant cell line that lends itself to in vitro study, (3) be reliable and predictable, (4) manifest survival differences, (5) allow for accurate treatment assessment, (6) be readily imaged, and (7) occur in similar background settings as the human disease. Over the past decades, numerous small animal models have been utilized for HCC studies; however, the development of new large animal models as qualified alternatives to murine models represents a key technology to advance research into human clinical trials.

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