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Chronic Heart Failure,CHF

Introduction: Heart failure is a syndrome caused by myocardial damage, which results from myocardial infarction, cardiomyopathy and inflammation, etc. Such myocardial damage leads to changes in myocardial structure and function, resulting in a low capability of ventricular filling and pumping. Chronic Heart Failure (CHF) refers to a long-term and consistent state of heart failure, which can be classified as stable, compensated, or decompensated. In general, the surgical models are achieved by either permanent ligation of left coronary artery, cardiac ischemia-reperfusion injury, or Transverse Aortic Constriction (TAC). It usually takes a few days or several weeks to develop into consistent and end-stage heart failure. This model can be used in basic medicine or new drugs preclinical research.

Animal requirement: Rats and mice - males are preferable. In special cases, female animals may be used. Age and weight can be adjusted accordingly.

Brief Protocol:

CHF can be achieved by three surgical models as below:
  • 1) Myocardial infarction induced by permanent ligation of the left coronary artery;
  • 2) Heart failure induced by cardiac ischemia-reperfusion injury;
  • 3) Heart failure induced by Transverse Aortic Constriction (TAC)

Turnaround time:

Chronic experiment. Postoperative time ranges from a few days to several weeks.

Pre/Post-operative management and delivery:

The whole process, including the breeding, surgery and post-operative management is carried out in Cyagen AAALAC-accredited SPF-level breeding facility.

Before the surgery, animals can be supplied by customers. Alternatively, Cyagen can help purchase Bio-standard animals (C57 mice, Wistar rats, or any commercially available GEMs worldwide). After full recovery from surgery, disease models can be delivered to customers by dedicated express.

Follow-up service:

  1. After-surgery routine observation: daily activities and diet intake are observed by full-time veterinarians, and pain relief treatment is applied accordingly.
  2. Cardiac ultrasonography: comprehensive evaluation of cardiac structure and function is achieved by ultra-high-definition small-animal-specific ultrasound machine. The evaluation of cardiac function before and after surgery (different periods of ventricular hypertrophy or heart failure development) includes the wall thickness (IVSs, IVSd, LVPWs, LVPWd), ventricular volume (LV Vols, LV Vold), ventricular lumen diameter (LVIDs, LVIDd), ejection fraction (EF%), fractional shortening (FS%) etc.. Customized ultrasonic tests can be performed upon request.
  3. Post-operative electrocardiogram detection: ECG records analysis at multiple time points.
  4. Blood sample collection: 0.7-1.0 mL venous blood, collected from adult mice or rats according to weight, can be used for various biochemical tests. The serum or plasma is stored in a -80⁰C refrigerator until delivery or biochemical detection.
  5. Cardiopulmonary specimen collection: Cardiopulmonary specimens are collected from different sections. The heart and lung specimens can be used to calculate the heart weight to body weight ratio and lung weight to body weight ratio. Besides, the specimens can be stored in a -80⁰C refrigerator or fixed with formalin for further pathological examination.

Animal ethical censorship and management

The Institutional Animal Care and Use Committee (IACUC) reviews the experimental protocol and manages the entire surgical procedure, including anesthesia, analgesia, animal preparation, and post-operative management.

Contact us:

For any surgical disease model, the strategy can be adjusted according to the scientific problems that researchers want to solve. If you have any special requests, please contact 86 20-31601779 or email apac-service@cyagen.com. Cyagen provides surgical model services personalized for your research goals - our senior technical team will develop a detailed experimental plan according to your needs and keep you updated throughout the model generation process.

References:

  1. L. H. Michael, M. L. Entman, C. J. Hartley, K. A. Youker, J. Zhu, S. R. Hall, H. K. Hawkins, K. Berens, and C. M. Ballantyne. Myocardial ischemia and reperfusion: a murine model. Am J. Physiol. 1995; 269 (Heart Circ. Physiol. 38): 2147-2154.
  2. Rongli Zhang, Douglas T. Hess, James R. Reynolds, Jonathan S. Stamler. Hemoglobin S-nitrosylation plays an essential role in cardioprotection. Journal of Clinical Investigation, 2016; 126(12): 4654-4658.
  3. Rongli Zhang, Yuyan Shen, Lin Zhou, Panjamaporn Sangwung, Hisashi Fujioka, Lilei Zhang, Xudong Liao. Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure. Journal of Molecular and Cellular Cardiology, 2017, 112: 64-73. doi:10.1016/j.yjmcc.2017.09.001
  4. Xudong Liao, Rongli Zhang, Yuan Lu, Domenick A Prosdocimo, Panjamaporn Sangwung, Lilei Zhang, Guangjin Zhou, Puneet Anand, Ling Lai, Teresa C Leone, Hisashi Fujioka, Fang Ye, Mariana G Rosca, Charles L Hoppel, P Christian Schulze, E Dale Abel, Jonathan S Stamler, Daniel P Kelly, Mukesh K Jain. Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis. Journal of Clinical Investigation, 2015;125(9):3461-3476. doi:10.1172/JCI79964.
  5. Lilei Zhang, Rongli Zhang, Chih-Liang Tien, Ricky E. Chan, Keiki Sugi, Chen Fu, Austin C. Griffin, Yuyan Shen, Thomas P. Burris, Xudong Liao, Mukesh K. Jain. REV-ERBα ameliorates heart failure through transcription repression. JCI Insight. 2017; 2(17): e95177. doi:10.1172/jci.insight.95177.
  6. Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T. Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E. Lemieux, Jonathan D. Brown, Deepak Srivastava, James E. Bradner, Timothy A. McKinsey, Saptarsi M. Haldar. BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure. Science Translational Medicine. 9(390): eaah5084 (2017).
  7. Priti Anand, Jonathan D. Brown, Charles Y. Lin, Jun Qi, Rongli Zhang, Pedro Calderon Artero, M. Amer Alaiti, Jace Bullard, Kareem Alazem, Kenneth B. Margulies, Thomas P. Coppola, Madeleine Lemieux, Jorge Plutzky, James E. Bradner, Saptarsi M. Haldar. BET bromodomains mediate transcriptional pause release in heart failure. Cell, 2013, 154, 569-582.
  8. Hiroki Hayashi, Douglas T. Hess, Rongli Zhang, Keiki Sugi, Huiyun Gao, Bea L. Tan, Dawn E. Bowles, Carmelo A. Milano, Mukesh K. Jain, Walter J. Koch, Jonathan S. Stamler. S-Nitrosylation of β-Arrestins Biases Receptor Signaling and Confers Ligand Independence. Molecular Cell, 2018, 70, 473-487.
  9. Xudong Liao, Yuyan Shen, Rongli Zhang, Keiki Sugi, Neelakantan T. Vasudevan, M. Amer Alaiti, David R. Sweet, Lin Zhou, Yulan Qing, Stanton L. Gerson, Chen Fu, Anthony Wynshaw-Boris, Rui Hu, Martin A. Schwartz, Hisashi Fujioka, Brian Richardson, Mark J. Cameron, Hiroki Hayashi, Jonathan S. Stamler, Mukesh K. Jain. Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy. Proceedings of the National Academy of Sciences, 2018; 115(20): E4661-E4669.
  10. Sanjoy K. Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J. Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B. Millar, Xudong Liao, Mukesh K. Jain, Mark R. Boyett, Elizabeth J. Cartwright, Holly A. Shiels, Xin Wang. Stress-Activated Kinase MKK7 Governs Epigenetics of Cardiac Repolarization for Arrhythmia Prevention. Circulation, 2017; 135:683-699
  11. Lilei Zhang, Domenick A. Prosdocimo, Xiaodong Bai, Chen Fu, Rongli Zhang, Frank Campbell, Xudong Liao, Jeff Coller, Mukesh K. Jain. KLF15 Establishes the Landscape of Diurnal Expression in the Heart. Cell Reports, 2015, 13:2368-2375.
  12. Lulu Sun, Chao Chen, Beibei Jiang, Yanli Li, Qiuping Deng, Min Sun, Xiangbo An, Xiao Yang, Ying Yang, Rongli Zhang, Yao Lu, De-Sheng Zhu, Yingqing Huo, Gen-Sheng Feng, Youyi Zhang, Jincai Luo. Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury. Basic Research in Cardiology, 2014; 109(4):420.
  13. Qionglin Liang, Xiaoping Liang, Yiming Wang, Yuanyuan Xie, Rongli Zhang, Xi Chen, Rong Gao, Yijun Cheng, Jun Wu, Qingbo Xu, Qingzhong Xiao, Xue Li, Shufeng Lv, Xuemei Fan, Honghyang Zhang, Qingli Zhang, Guoan Luo. Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode. Journal of Translational Medicine, 2012; 10: 26.
  14. Peidong Han, Wenfeng Cai, Yanru Wang, Chi Keung Lam, Demetrios Arvanitis, Vivek Singh, Shan Chen, Huilang Zhang, Rongli Zhang, Heping Cheng, Evangelia Kranias. Catecholaminergic induced arrhythmias in failing cardiomyocytes associated with human HRCS96A variant overexpression. Am J Physiol Heart Circ Physiol, 2011; 301:H1588-H1595.
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