Small Animal Physiology Core
The Core provides support for animal studies involving cardiovascular diseases and measuring in vivo cardiac physiology.
We have developed and standardized many small animal surgical models and measuring instruments suitable for translational research. The Core is located in the Center for Translational Medicine on the 5th floor of Jefferson Alumni Hall and is under the direction of Nadan Wang, MS.
The Core provides numerous state-of-the-art approaches to use small animals as models for human disease. We offer a variety of invasive surgical procedures and noninvasive ultrasound imaging services for comprehensive evaluation of cardiovascular phenotypes of transgenic and knockout mice. Although current services emphasize models of cardiovascular disease, the core has expertise in surgery and model development to support a wide range of protocols.
The Core currently provides the following services for Physiological Function Assessment and Animal Microsurgical Models.
If you have a research project that would benefit from our services, please fill out the Service Request Form. We would be happy to work with you on developing any animal models or new surgical procedures that fit your research. For additional information, please contact Dr. Raymond Penn, Director, Center for Translational Medicine.
Physiological Function Assessment
Echocardiography (including 2-D, M-mode, Doppler flows, or complete analysis) for evaluating cardiac structure and function.
- Echocardiography in adult, neonatal and fetal mice
- Carotid artery ultrasound imaging
Invasive hemodynamic measurements of in vivo cardiac function and analysis. Indices of left / right ventricular contractile performance are determined in mice under isoflurane anesthesia by introducing a 1.4 Fr. Millar catheter into the right carotid artery / right jugular vein and gently advancing into left / right ventricular cavity. Pressure waves are recorded and analyzed using a data acquisition system (LabChart 7, AD Instruments).
Animal Microsurgical Models
Common carotid artery ligation completely ceases blood flow through the common carotid and downstream branches and induces vascular smooth muscle cell proliferation and neointimal and medial vessel wall growth.
Hindlimb ischemia model is a classic mouse model of angiogenesis, and could be used to evaluate therapeutic angiogenesis with gene or stem cell therapy. Also, it is a model of peripheral arterial disease. The femoral artery ligation provides a simpler model of ischemia with low mortality rate.
Rat carotid artery balloon injury model using the balloon catheter completely removes the endothelium and creates an injury site in the operated artery. The process allows for investigation of the response to experimentally induced injury, including the vascular smooth muscle cell proliferation, migration, apoptosis; and vascular endothelial cell regeneration.
Transverse aortic constriction (TAC) model in mice is a commonly used animal model for pressure overload-induced cardiac hypertrophy and heart failure. This model can be used to research the left ventricular hypertrophic response and remodeling under chronic pressure overload or heart failure development.
Myocardial infarction (MI) model is by permanent ligation of the left anterior descending coronary artery (LAD) for adult/newborn mice. The LAD formed a local region of permanent ischemia in the heart. It is a useful model of ischemic heart failure, and can be used to study heart regeneration.
Mouse heart ischemia reperfusion (I/R) is a mouse model to induce acute myocardial infarction for a short time, and then reperfuse the ischemic tissues by release of the ligation site. Reperfusion produces tissue damage on ischemic myocardium, including inflammation, oxidative damage and apoptosis.
Sepsis model was created more than 30 years ago, and now is the most frequently used model of sepsis. Usually the mice develop typical symptoms of sepsis after cecum ligation and puncture. This model is used to study the systemic inflammatory response and immunosuppression.
Osmotic pump implantation is used to control systemic delivery to the mouse or rat. The minipumps deliver a wide range of experimental agents, including siRNA, peptides, growth factors, cytokines, drugs, and antibodies, for durations ranging from one day to six weeks.
Publications that Involved the Core
- Du S, Zhou L, Alexander GS, Park K, Yang L, Wang N, Ma X, Wang Y, Dicker AP, Lu B. (2017) PD-1 modulates radiation-induced cardiac toxicity through cytotoxic T lymphocytes. J Thorac Oncol. pii: S1556-0864(17)33081-2.
- Ajay P Nayak, Deepak A Deshpande, Roslyn Yi, Nadan Wang, Raymond B Penn (2017) Targeting GPCR (OGR1) with desmethyl benzodiazepine drugs in an allergen-induced murine asthma model. 10th Annual Young Investigator’s Meeting on Smooth Muscle in Airways & Vascular Disease
- Sharma P, Yi R, Nayak AP, Wang N, Tang F, Knight MJ, Pan S, Oliver B, Deshpande DA. (2017) Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice. Sci Rep. 7:46166.
- Paillard M, Csordás G, Szanda G, Golenár T, Debattisti V, Bartok A, Wang N, Moffat C, Seifert EL, Spät A, Hajnóczky G. (2017) Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU. Cell Rep. 18(10):2291-2300.
- Yan G, Zhu N, Huang S, Yi B, Shang X, Chen M, Wang N, Zhang GX, Talarico JA, Tilley DG, Gao E, Sun J. (2015) Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response to Beta-Adrenergic Stimulation. Mol Cell Biol. 35(19): 3312-23.
- Shah D, Romero F, Duong M, Wang N, Paudyal B, Suratt BT, Kallen CB, Sun J, Zhu Y, Walsh K, Summer R. (2015) Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury. Sci Rep. 5:11362.
- Pan S, Wang N, Bisetto S, Yi B, Sheu SS. (2015) Downregulation of adenine nucleotide translocator 1 exacerbates tumor necrosis factor-α-mediated cardiac inflammatory responses. Am J Physiol Heart Circ Physiol. 308(1): H39-48.
- Huo Y, Yi B, Chen M, Wang N, Chen P, Guo C, Sun J. (2014) Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation. Biochem Pharmacol. 92(4): 590-8.
- Pan S, Wang N, Sheu SS. (2014) A Protective Role Of Adenine Nucleotide Translocator 1 In The Inflammatory Response Following Myocardial Infarction. Circ Res. 115: A59.
- Pan S, Wang N, Bisetto S, Yi B, Sheu SS. (2014) Down-regulation of adenine nucleotide translocator 1 exacerbates cardiac inflammation. 35th ISHR North American Section Meeting
- Li P, Zhu N, Yi B, Wang N, Chen M, You X, Zhao X, Solomides CC, Qin Y, Sun J. (2013) MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation. Circ Res. 113(10): 1117-27.
- Eisner V, Cupo RR, Gao E, Csordás G, Slovinsky WS, Paillard M, Cheng L, Ibetti J, Chen SR, Chuprun JK, Hoek JB, Koch WJ, Hajnóczky G.(2017) Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity. Proc Natl Acad Sci USA. 114(5):E859-E868.
- Zhang Y, Zhao J, Li R, Lau WB, Yuan YX, Liang B, Li R, Gao EH, Koch WJ, Ma XL, Wang YJ. (2015) AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings. Am J Physiol Endocrinol Metab. 309(3): E275-82
- Wang Y, Gao E, Lau WB, Wang Y, Liu G, Li JJ, Wang X, Yuan Y, Koch WJ, Ma XL. (2015) G-protein-coupled receptor kinase 2-mediated desensitization of adiponectin receptor 1 in failing heart. Circulation. 131(16): 1392-404.