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Animal Models for the Study of Cardiovascular Disease

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A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 43990

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Dr. Manuel Zarzoso

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Guest Editor

Department of Physiotherapy, Universitat de València, 46010 Valencia, Spain
Interests: laboratory animals; experimental models; metabolic syndrome; arrhythmias; basic cardiac electrophysiology

Special Issue Information

Dear Colleagues,

Cardiovascular disease is one of the leading causes of death worldwide. Thanks to animal models, basic research has made a substantial contribution to the knowledge of cardiovascular risk factors and disease pathogenesis, enabling the development of diagnostic techniques and the establishment of therapeutic strategies. Even though animal models never completely resemble the human clinical situation, they can provide important information on the pathologic mechanisms of the disease, allowing the study of several variables under very controlled conditions and applying procedures that are difficult to use in clinical conditions, always prioritizing animal welfare and humane treatment.

On behalf of Animals, we are organizing a Special Issue focused on the use of animal models for the study of cardiovascular disease. Animals is an international peer-reviewed open access journal devoted entirely to animals, including zoology and veterinary sciences. For detailed information on the journal, we refer you to the website: https://www.mdpi.com/journal/animals.

We welcome submissions of original research or review papers, focused on different aspects of animal models applied in the study of cardiovascular disease, including (but not limited to) description and characterization of novel experimental models, the study of pathological mechanisms underlying the different manifestations of cardiovascular disease, and novel methodologies, diagnostic techniques, medical and surgical treatments applied in small or large animals.

Dr. Manuel Zarzoso
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Animals is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

experimental models
hypertension
arrhythmias
cardiac fibrillation
heart failure
myocardial ischemia
blood vessels
cerebrovascular disease
hypercholesterolemia
diabetes

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Published Papers (9 papers)

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Research

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16 pages, 3743 KiB

Open AccessArticle

Cardiovascular Performance Measurement in Water Fleas by Utilizing High-Speed Videography and ImageJ Software and Its Application for Pesticide Toxicity Assessment

by Fiorency Santoso, Viacheslav V. Krylov, Agnes L. Castillo, Ferry Saputra, Hong-Ming Chen, Hong-Thih Lai and Chung-Der Hsiao

Animals 2020, 10(9), 1587; https://doi.org/10.3390/ani10091587 - 5 Sep 2020

Cited by 24 | Viewed by 9370

Abstract

Water fleas are a good model for ecotoxicity studies, and were proposed for this purpose by the United States Environmental Protection Agency, due to their easy culture, body transparency, and high sensitivity to chemical pollution. Cardiovascular function parameters are usually used as an indicator of toxicity evaluation. However, due to the nature of the heart and blood flow, and the speed of the heartbeat, it is difficult to perform precise heartbeat and blood flow measurements with a low level of bias. In addition, the other cardiovascular parameters, including stroke volume, cardiac output, fractional shortening, and ejection fraction, have seldom been carefully addressed in previous studies. In this paper, high-speed videography and ImageJ-based methods were adopted to analyze cardiovascular function in water fleas. The heartbeat and blood flow for three water flea species, Daphnia magna, Daphnia silimis, and Moina sp., were captured by high-speed videography and analyzed using open-source ImageJ software. We found the heartbeat is species-dependent but not size-dependent in water fleas. Among the three water fleas tested, D. magna was identified as having the most robust heartbeat and blood flow rate, and is therefore suitable for the ecotoxicity test. Moreover, by calculating the diameter of the heart, we succeeded in measuring other cardiovascular parameters. D. magna were challenged with temperature changes and a pesticide (imidacloprid) to analyze variations in its cardiovascular function. We found that the heartbeat of D. magna was temperature-dependent, since the heartbeat was increasing with temperature. A similar result was shown in the cardiac output parameter. We also observed that the heartbeat, cardiac output, and heartbeat regularity are significantly reduced when exposed to imidacloprid at a low dose of 1 ppb (parts per billion). The blood flow rate, stroke volume, ejection fraction, and fractional shortening, on the contrary, did not display significant changes. In conclusion, in this study, we report a simple, highly accurate, and cost-effective method to perform physiological and toxicological assessments in water fleas. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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19 pages, 5903 KiB

Open AccessArticle

Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits

by Patricia Genovés, Óscar J. Arias-Mutis, Germán Parra, Luis Such-Miquel, Manuel Zarzoso, Irene Del Canto, Carlos Soler, Ana Díaz, Eva Blanch, Antonio Alberola, Luis Such and Francisco J. Chorro

Animals 2020, 10(9), 1576; https://doi.org/10.3390/ani10091576 - 4 Sep 2020

Cited by 4 | Viewed by 4028

Abstract

A chronic model of acute myocardial infarction was developed to study the mechanisms involved in adverse postinfarction ventricular remodeling. In an acute myocardial infarction (AMI), the left circumflex coronary artery of New Zealand White rabbits (n = 9) was occluded by ligature for 1 h, followed by reperfusion. A specific care protocol was applied before, during, and after the intervention, and the results were compared with those of a sham operated group (n = 7). After 5 weeks, programmed stimulation and high-resolution mapping were performed on isolated and perfused hearts using the Langendorff technique. The infarct size determined by 2,3,5-triphenyltetrazolium chloride inside of the area at risk (thioflavin-S) was then determined. The area at risk was similar in both groups (54.33% (experimental infarct group) vs. 58.59% (sham group), ns). The infarct size was 73.16% as a percentage of the risk area. The experimental infarct group had a higher inducibility of ventricular arrhythmias (100% vs. 43% in the sham group, p = 0.009). A reproducible chronic experimental model of myocardial infarction is presented in which the extent and characteristics of the lesions enable the study of the vulnerability to develop ventricular arrhythmias because of the remodeling process that occurs during cardiac tissue repair. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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15 pages, 511 KiB

Open AccessArticle

Assessment of DNA Methylation and Oxidative Changes in the Heart and Brain of Rats Receiving a High-Fat Diet Supplemented with Various Forms of Chromium

by Wojciech Dworzański, Ewelina Cholewińska, Bartosz Fotschki, Jerzy Juśkiewicz, Piotr Listos and Katarzyna Ognik

Animals 2020, 10(9), 1470; https://doi.org/10.3390/ani10091470 - 21 Aug 2020

Cited by 10 | Viewed by 3150

Abstract

The aim of the study was to determine how feeding rats a high-fat diet supplemented with various forms of chromium affects DNA methylation and oxidation reactions as well as the histology of heart and brain tissue. The rats received standard diet or high-fat diet and chromium at 0.3 mg/kg body weight (BW) in form of chromium (III) picolinate, chromium (III)-methionine, or nano-sized chromium. The content of malondialdehyde (MDA), protein carbonyl (PC), and 8-hydroxydeoxyguanosine (8-OHDG), the level of global DNA methylation and the activity of selected DNA repair enzymes were determined in the blood. In the brain and heart, the content of MDA, PC, 8-OHDG, and levels of global DNA methylation were determined. The brain was subjected to histological examination. The use of a high-fat diet was found to intensify epigenetic changes and oxidation reactions in the heart and brain. It was concluded that epigenetic changes and oxidation of lipids, proteins, and DNA in the heart and brain of rats resulting from the use of a high-fat diet cannot be limited by supplementing the diet with chromium. It was established that the use of chromium to supplement a high-fat diet intensifies the negative epigenetic and oxidative changes in the heart and brain, especially in the case of chromium nanoparticles. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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15 pages, 3552 KiB

Open AccessArticle

Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies

by Armando Pérez de Prado, Claudia Pérez-Martínez, Marta Regueiro-Purriños, Carlos Cuellas-Ramón, María López-Benito, José Manuel Gonzalo-Orden, Rodrigo Estévez-Loureiro, Ana Isabel Cortina-Rivero, David Viñuela-Baragaño, José R Altonaga, Armando Tellez and Felipe Fernández-Vázquez

Animals 2020, 10(9), 1446; https://doi.org/10.3390/ani10091446 - 19 Aug 2020

Viewed by 2555

Abstract

New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity^® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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14 pages, 306 KiB

Open AccessArticle

Echocardiographic Findings in Canine Model of Chagas Disease Immunized with DNA Trypanosoma cruzi Genes

by Olivia Rodríguez-Morales, Francisco-Javier Roldán, Jesús Vargas-Barrón, Enrique Parra-Benítez, María de Lourdes Medina-García, Emilia Vergara-Bello and Minerva Arce-Fonseca

Animals 2020, 10(4), 648; https://doi.org/10.3390/ani10040648 - 9 Apr 2020

Cited by 5 | Viewed by 2699

Abstract

Chagas disease (ChD) is considered an emerging disease in the USA and Europe. Trypanosoma cruzi genes encoding a trans-sialidase protein and an amastigote-specific glycoprotein were tested as vaccines in canine model. The aim for this study was determining the prophylactic effect of these genes in experimentally infected dogs by echocardiography evaluation to compare with our findings obtained by other techniques published previously. Low fractional-shortening values of non-vaccinated dogs suggested an impairment in general cardiac function. Low left ventricular ejection fraction values found in infected dogs suggested myocardial injury regardless of whether they were vaccinated. Low left ventricular diastolic/systolic diameters suggested that progressive heart damage or heart dilation could be prevented by DNA vaccination. Systolic peak time was higher in non-vaccinated groups, increasing vulnerability to malignant arrhythmias and sudden death. High left ventricular volume suggested a decrease in wall thickness that might lead to increased size of the heart cavity, except in the pBCSP plasmid-vaccinated dogs. There was an echocardiographic evidence of left ventricular dilation and reduction in systolic function in experimental chagasic dogs. Echocardiography allowed a more complete follow-up of the pathological process in the living patient than with other techniques like electrocardiography, anatomopathology, and histopathology, being the method of choice for characterizing the clinical stages of ChD. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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17 pages, 6202 KiB

Open AccessArticle

Thymoquinone-PLGA-PVA Nanoparticles Ameliorate Bleomycin-Induced Pulmonary Fibrosis in Rats via Regulation of Inflammatory Cytokines and iNOS Signaling

by Sultan A. M. Saghir, Naif A. Al-Gabri, Asmaa F. Khafaga, Nahla H. El-shaer, Khaled A. Alhumaidh, Mohamed F. Elsadek, Badreldin M. Ahmed, Daniyah M. Alkhawtani and Mohamed E. Abd El-Hack

Animals 2019, 9(11), 951; https://doi.org/10.3390/ani9110951 - 11 Nov 2019

Cited by 35 | Viewed by 5410

Abstract

Pulmonary fibrosis is considered one of the most chronic interstitial illnesses which are not easily treated. thymoquinone’s (TQ) benefits are still partly problematic due to poor water solubility; therefore, it was loaded onto PLGA-PVA carriers. This study aimed to evaluate the potential effect of TQ-PLGA-PVA nanoparticles (TQ-PLGA-PVA-NPs) on pulmonary fibrosis induced by bleomycin in albino rats. Forty male rats were randomized into four groups. The first group served as the control group; the second and the third groups received bleomycin intratracheally, whereas the third group received TQ-PLGA-PVA-NPs after 4 weeks from bleomycin administration. The fourth group was administrated TQ-PLGA-PVA-NPs alone. The designed nanoparticles appeared around 20 nm size (10–30 nm), had a spherical shape, and had 80% encapsulation efficiency. The histological examination of rats simultaneously treated with TQ-PLGA-PVA-NPs and bleomycin revealed reduction in the thickness of the alveolar septa and improvement of the other lung structures, with the presence of lymphocytes admixed with exfoliated epithelium in a few lumina remaining. Ultrastructural findings revealed marked collagenolysis and the release of nanoparticles from ruptured pneumocytes within the alveolar septa after 14 days from TQ-PLGA-PVA-NPs administration. Very active pneumocyte types II were seen in the TQ-PLGA-PVANP group. Additionally, immunohistochemical expression of inducible nitric oxide (iNOS) and estimation of inflammatory cytokines in lung tissues including interleukin 10 (IL 10) and transforming growth factor-beta (TGF-β1) confirmed the antioxidant and anti-inflammatory effects of TQ-PLGA-PVANPs. The study concluded that TQ-PLGA-PVA-NPs could attenuate the bleomycin-induced pulmonary fibrosis, through the inhibition of lung inflammation and the suppression of bleomycin- induced oxidative stress. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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Review

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12 pages, 1506 KiB

Open AccessReview

Large Animal Models of Heart Failure: Reduced vs. Preserved Ejection Fraction

by Christopher J. Charles, Miriam T. Rademaker, Nicola J. A. Scott and A. Mark Richards

Animals 2020, 10(10), 1906; https://doi.org/10.3390/ani10101906 - 18 Oct 2020

Cited by 18 | Viewed by 6767

Abstract

Heart failure (HF) is the final common end point of multiple metabolic and cardiovascular diseases and imposes a significant health care burden worldwide. Despite significant improvements in clinical management and outcomes, morbidity and mortality remain high and there remains an indisputable need for improved treatment options. The pathophysiology of HF is complex and covers a spectrum of clinical presentations from HF with reduced ejection fraction (HFrEF) (≤40% EF) through to HF with preserved EF (HFpEF), with HFpEF patients demonstrating a reduced ability of the heart to relax despite an EF maintained above 50%. Prior to the last decade, the majority of clinical trials and animal models addressed HFrEF. Despite growing efforts recently to understand underlying mechanisms of HFpEF and find effective therapies for its treatment, clinical trials in patients with HFpEF have failed to demonstrate improvements in mortality. A significant obstacle to therapeutic innovation in HFpEF is the absence of preclinical models including large animal models which, unlike rodents, permit detailed instrumentation and extensive imaging and sampling protocols. Although several large animal models of HFpEF have been reported, none fulfil all the features present in human disease and few demonstrate progression to frank decompensated HF. This review summarizes well-established models of HFrEF in pigs, dogs and sheep and discusses attempts to date to model HFpEF in these species. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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25 pages, 711 KiB

Open AccessReview

Optimizing the Use of iPSC-CMs for Cardiac Regeneration in Animal Models

by Alexandra Bizy and Matthew Klos

Animals 2020, 10(9), 1561; https://doi.org/10.3390/ani10091561 - 2 Sep 2020

Cited by 11 | Viewed by 4973

Abstract

Heart failure (HF) is a common disease in which the heart cannot meet the metabolic demands of the body. It mostly occurs in individuals 65 years or older. Cardiac transplantation is the best option for patients with advanced HF. High numbers of patient-specific cardiac myocytes (CMs) can be generated from induced pluripotent stem cells (iPSCs) and can possibly be used to treat HF. While some studies found iPSC-CMS can couple efficiently to the damaged heart and restore cardiac contractility, almost all found iPSC-CM transplantation is arrhythmogenic, thus hampering the use of iPSC-CMs for cardiac regeneration. Studies show that iPSC-CM cultures are highly heterogeneous containing atrial-, ventricular- and nodal-like CMs. Furthermore, they have an immature phenotype, resembling more fetal than adult CMs. There is an urgent need to overcome these issues. To this end, a novel and interesting avenue to increase CM maturation consists of modulating their metabolism. Combined with careful engineering and animal models of HF, iPSC-CMs can be assessed for their potential for cardiac regeneration and a cure for HF. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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14 pages, 1347 KiB

Open AccessReview

Exercise Training Protocols in Rabbits Applied in Cardiovascular Research

by Wilson M. Lozano, Germán Parra, Oscar J. Arias-Mutis and Manuel Zarzoso

Animals 2020, 10(8), 1263; https://doi.org/10.3390/ani10081263 - 24 Jul 2020

Cited by 2 | Viewed by 2864

Abstract

Rabbit exercise protocols allow for the evaluation of physiological and biomechanical changes and responses to episodes of acute or chronic exercise. The observed physiological changes are normal responses to stress, that is, adaptive responses to maintain or restore homeostasis after acute exercise. Indeed, the rabbit model is advantageous since (a) it has important physiological similarities in terms of the functioning of multiple organ systems, and can quickly induce alterations in pathophysiological conditions that resemble those of humans, and (b) it allows the implementation of a low-cost model in comparison with other large animals. When designing an exercise training protocol for rabbits, it is important to consider variables such as race, gender, age and, especially, training parameters such as volume, intensity, or rest, among others, to determine the outcome of the research. Therefore, the objective of this review is to identify and analyze exercise training protocols in rabbits in different experimental applications and the various physiological adaptations that are presented, with special focus in cardiovascular adaptations. Full article

(This article belongs to the Special Issue Animal Models for the Study of Cardiovascular Disease)

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