Submit manuscript...
eISSN: 2471-139X

Anatomy & Physiology

Editorial Volume 2 Issue 1

Animal models in cardiovascular diseases

Jonathan Fox, Mini Chandra, Manikandan Panchatcharam, Sumitra Miriyala

Department of Cell biology and Anatomy, Louisiana State University Health Sciences Center, USA

Correspondence: Sumitra Miriyala, Department of Cell biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA

Received: January 11, 2016 | Published: January 18, 2016

Citation: Fox J, Chandra M, Panchatcharam M. Animal models in cardiovascular diseases. MOJ Anat Physiol. 2016;2(1):17–18. DOI: 10.15406/mojap.2016.02.00034

Download PDF


The use of animal models, which can range from mice to even fruit flies,1 has added to increasing our Understanding and providing new methodologies focused to advance the diagnostic and treatment of certain pathologies. A number of models have been shaped to address cardiovascular complications, however factors such as genetics and environment, play a role in cardiovascular pathophysiology and have made it quite difficult to match a particular disease, with just a single experimental model. The development of animal models of cardiovascular diseases (CVD), including cardiac and athero thrombotic diseases, has provided us today with important insights into the pathophysiology, and they were found to be essential tools to evaluate new therapeutic strategies to predict and to prevent these complications.2 Coronary artery ligation is a commonly used model of myocardial infarction for assessing intramyocardial therapeutic delivery of genes, cells or proteins. In this procedure, Zaragoza et al.3 explained that first a thoracotomy is performed on the anesthetized animal, and the heart is rapidly exteriorized by gentle pressure on the right side of the thorax. The coronary artery is either ligated or heat cauterized between the pulmonary artery outflow tract and the left atrium. The heart is then returned to its normal position and the thorax immediately closed.3 There are two main ligation models, permanent left main descending coronary artery (LCA) occlusion to induce a myocardial infarction (MI) and a temporary coronary artery occlusion to induce ischemia/reperfusion injury (IR).4 Of course one obvious drawback is that animals have different physiologies than humans,5 so as researchers we must take this into consideration. However there are some benefits to this model procedure such as undamaged pectoral muscles, which is significant because these muscles are essential to cover the opening once the heart has been returned to the thoracic space and excludes the stitching of the muscle. In junction with the coronary ligation model, administration of the drug isoproterenol is used since in certain dosages, the drug can cause heart lesions similar to myocardial infarction.6

In low dosage, Isoproterenol is used primarily for the treatment of cardiovascular problems such as bradycardia (slow heart rate) or heart block (condition that causes a fault with the SA node due to an obstruction).By the activation of β1 and β2-receptors in the heart, it can induce a chronotropic, dromotropic, and inotropic effect. However, associated with the drug are its negative cardiovascular side effects such as tachycardia or cardiac dysrhythmias. Isoproterenol has been observed to produce certain biochemical, electrophysiological and histological alterations in the heart. In a study done by Jaehnig et al.7 and Zhengrong et al.8 showed that in rabbits with electrical storm (recurrent multiple ventricular fibrillation episodes associated with myocardial infarction) and ventricular arrhythmia, Isoproterenol was able to prolong action potential duration and increased type calcium current. Thus showing the important role of isoproterenol in the mechanism of cardio electrophysiology. The genetic and physiological similarities between animals, like mice, and humans have focused considerable attention on potential models of human health and diseases.9 In the last few decades, there has been generation of genetic animal models to observe disease conditions. Specifically, researchers are now able to use gene alterations which can control expression of an animal model used. Using site-specific recombinase (SSR) systems, we can knock out the target gene within a particular cell type at certain developmental phases (conditional knockout).10 The Cre-lox recombination system is widely used to carry out deletions, insertions, translocations and inversions at specific sites in the DNA. Another successful method used for conditional gene expression is the tetracycline (Tet)-inducible system, which is responsible for the reversibly turning on or off of genes in the presence of the antibiotic tetracycline or its derivatives.11 This system is similar to the Cre-lox systems except for the fact that the Tet- inducible system is reversible (which makes this system an advantage to the Cre-lox system). Gene knockout animal models are proven to be an important component in conjunction with transgenic lines of mice as a means of generating “humanized” mouse models as part of drug discovery strategies.9,12‒17



Conflict of interest

Author declares that there is no conflict of interest.


  1. Chorro FJ, Such-Belenguer L, López-Merino V. Animal models of cardiovascular disease. Rev Esp Cardiol. 2016;62(1):69‒84.
  2. Chandrasekera PC, Pippin JJ. The Human Subject: an Integrative Animal Model for the 21st Century Heart Failure Research. Am J Transl Res. 2015;7(9):1636‒1647.
  3. Zaragoza C, Gomez-Guerrero C, Martin-Ventura JL, et al. Animal Models of Cardiovascular Disease. J Biomed Biotechnol. 2011;2011:497841.
  4. Gao E, Lei YH, Shang X, et al. A Novel and Efficient Model of Coronary Artery Ligation and Myocardial Infarction in the Mouse. Circ Res. 2010;107(12):1445‒1453.
  5. Halapas A, Papalois A, Stauropoulou A, et al. In VivoModels for Heart Failure Research. In Vivo. 2008;22(6):767‒780.
  6. Rahmathulla Mahammad, Devi Kodidhela Lakshmi. Origination and Development of Isoproterenol Induced Myocardial Infarction in Male Wistar Rats. International Research Journal of Pharmacy. 2013;4(5):26‒35.
  7. Jaehnig EJ, Heidt AB, Greene SB, et al. Increased Susceptibility to Isoproterenol-Induced Cardiac Hypertrophy and Impaired Weight Gain in Mice Lacking the Histindine-Rich Calcium Binding Protein. Mol Cell Biol. 2006;26(24):9315‒9326.
  8. Zhengrong Huang, Wihua Li, et al. Studies on Ionic Mechanisms of the Effects of Isoproterenol on Brugada Syndrome. Heart. 2011;97:A35.
  9. Doyle A, McGarry MP, Lee NA, et al. The Construction of Transgentic and Gene Knockout/Knockin Mouse Models of Human Diseases. Transgenic Res. 2012;21(2):327‒349.
  10. Zhang J, Zhao J, Jiang WJ, et al. Conditional Gene Manipulation: Cre-ating a New Biological Era. J Zhejiang Univ Sci. 2012;13(7):511‒524.
  11. Sun Y, Chen X, Xiao D. Tetracycline-Inducible Expression Systems: New Strategies and Practices in the Transgenic Mouse Modeling. Acta Biochem Biophys Sin (Shanghai). 2007;39(4):235‒246.
  12. Hasenfuss G. Animal Models Cardiovascular Disease, Heart Failure and hypertrophy. Cardiovasc Res. 1998;39(1):60‒76.
  13. Klocke R, Tian W, Kuhlmann MT, et al. Surgical Animal Models of Heart Failure Related to Coronary Heart Disease. Cardiovasc Res. 2009;74(1):29‒38.
  14. Grimm D, Elsner D, Schunkert H, et al. Development of Heart Failure Following Isoproterenol Administration in the Rat: Role of the Renin-Angiotensin System. Cardiovasc Res. 1998;37(1):91‒100.
  15. Marecki JC, Parajuli N, Crow JP, et al. The Use of the Cre/loxP System to Study Oxidative Stress in Tissue-Specific Manganese Superoxide Dismutase Knockout Models. Antioxid Redox Signal. 2014;20(10):1655‒1670.
  16. Holley AK, Bakthavatchalu V, Velez-Roman JM, et al. Manganese Superoxide Dismutase: Guardian of the Powerhouse. Int J Mol Sci. 2001;12(10):7114‒7162.  
  17. Brenchenridge Ross. Animal Models of Myocardial Disease. Animal Models For the Study of Human Disease. 2013:145‒164.
Creative Commons Attribution License

©2016 Fox, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.