Advertisement

Isoproterenol-Induced Heart Failure Mouse Model Using Osmotic Pump Implantation

  • Sunny C. Chang
  • Shuxun Ren
  • Christoph D. Rau
  • Jessica J. Wang
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1816)

Abstract

Isoproterenol is used widely for inducing heart failure in mice. Isoproterenol is a nonselective beta-adrenergic agonist. The acute model mimics stress-induced cardiomyopathy. The chronic model mimics advanced heart failure in humans. In this chapter, we describe a protocol that we used to induce heart failure in 100+ strains of inbred mice. Techniques on surgical pump implantation and echocardiography are described in detail. We also discuss the impact of drug dosage, duration, mortality, age, gender, and strain on cardiac remodeling responses. The success of model creation may be assessed by echocardiogram or molecular markers. This chapter may be relevant to those who are interested in using this heart failure model.

Key words

Heart failure Isoproterenol Mouse model Cardiac remodeling Mouse strains Echocardiography 

Notes

Acknowledgments

The discussed protocol has been developed in the laboratory of Dr. Yibin Wang.

References

  1. 1.
    Balakumar P, Singh AP, Singh M (2007) Rodent models of heart failure. J Pharmacol Toxicol Methods 56(1):1–10CrossRefPubMedGoogle Scholar
  2. 2.
    Yoshikawa T (2015) Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and pathophysiology. Int J Cardiol 182:297–303CrossRefPubMedGoogle Scholar
  3. 3.
    Kono T, Sabbah HN (2014) Takotsubo cardiomyopathy. Heart Fail Rev 19(5):585–593CrossRefPubMedGoogle Scholar
  4. 4.
    Shao Y, Redfors B, Stahlman M, Tang MS, Miljanovic A, Mollmann H, Troidl C, Szardien S, Hamm C, Nef H, Boren J, Omerovic E (2013) A mouse model reveals an important role for catecholamine-induced lipotoxicity in the pathogenesis of stress-induced cardiomyopathy. Eur J Heart Fail 15(1):9–22CrossRefPubMedGoogle Scholar
  5. 5.
    Kudej RK, Iwase M, Uechi M, Vatner DE, Oka N, Ishikawa Y, Shannon RP, Bishop SP, Vatner SF (1997) Effects of chronic beta-adrenergic receptor stimulation in mice. J Mol Cell Cardiol 29(10):2735–2746CrossRefPubMedGoogle Scholar
  6. 6.
    Zhuo XZ, Wu Y, Ni YJ, Liu JH, Gong M, Wang XH, Wei F, Wang TZ, Yuan Z, Ma AQ, Song P (2013) Isoproterenol instigates cardiomyocyte apoptosis and heart failure via ampk inactivation-mediated endoplasmic reticulum stress. Apoptosis 18(7):800–810CrossRefPubMedGoogle Scholar
  7. 7.
    El-Demerdash E, Awad AS, Taha RM, El-Hady AM, Sayed-Ahmed MM (2005) Probucol attenuates oxidative stress and energy decline in isoproterenol-induced heart failure in rat. Pharmacol Res 51(4):311–318CrossRefPubMedGoogle Scholar
  8. 8.
    Rau CD, Wang J, Avetisyan R, Romay MC, Martin L, Ren S, Wang Y, Lusis AJ (2015) Mapping genetic contributions to cardiac pathology induced by beta-adrenergic stimulation in mice. Circ Cardiovasc Genet 8(1):40–49CrossRefPubMedGoogle Scholar
  9. 9.
    Wang JJ, Rau C, Avetisyan R, Ren S, Romay MC, Stolin G, Gong KW, Wang Y, Lusis AJ (2016) Genetic dissection of cardiac remodeling in an isoproterenol-induced heart failure mouse model. PLoS Genet 12(7):e1006038CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cross HR, Murphy E, Koch WJ, Steenbergen C (2002) Male and female mice overexpressing the beta(2)-adrenergic receptor exhibit differences in ischemia/reperfusion injury: role of nitric oxide. Cardiovasc Res 53(3):662–671CrossRefPubMedGoogle Scholar
  11. 11.
    Klingman GI, McKay G, Ward A, Morse L (1973) Chronic isoproterenol treatment of mice: effects on catecholamines and rectal temperature. J Pharm Sci 62(5):798–801CrossRefPubMedGoogle Scholar
  12. 12.
    Ma S, Yang D, Wang K, Tang B, Li D, Yang Y (2012) Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2. Mol Med Rep 6(1):145–150PubMedGoogle Scholar
  13. 13.
    Berthonneche C, Peter B, Schupfer F, Hayoz P, Kutalik Z, Abriel H, Pedrazzini T, Beckmann JS, Bergmann S, Maurer F (2009) Cardiovascular response to beta-adrenergic blockade or activation in 23 inbred mouse strains. PLoS One 4(8):e6610CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Oudit GY, Crackower MA, Eriksson U, Sarao R, Kozieradzki I, Sasaki T, Irie-Sasaki J, Gidrewicz D, Rybin VO, Wada T, Steinberg SF, Backx PH, Penninger JM (2003) Phosphoinositide 3-kinase gamma-deficient mice are protected from isoproterenol-induced heart failure. Circulation 108(17):2147–2152CrossRefPubMedGoogle Scholar
  15. 15.
    Galindo CL, Skinner MA, Errami M, Olson LD, Watson DA, Li J, McCormick JF, McIver LJ, Kumar NM, Pham TQ, Garner HR (2009) Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure. BMC Physiol 9:23CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ren J, Yang L, Tian W, Zhu M, Liu J, Lu P, Li J, Yang L, Qi Z (2015) Nitric oxide synthase inhibition abolishes exercise-mediated protection against isoproterenol-induced cardiac hypertrophy in female mice. Cardiology 130(3):175–184CrossRefPubMedGoogle Scholar
  17. 17.
    Yang YH, Fang HL, Zhao M, Wei XL, Zhang N, Wang S, Lu Y, Yu XJ, Sun L, He X, Li DL, Liu JJ, Zang WJ (2017) Specific alpha7 nicotinic acetylcholine receptor agonist ameliorates isoproterenol-induced cardiac remodelling in mice through tgf-beta1/smad3 pathway. Clin Exp Pharmacol Physiol 44:1192–1200CrossRefPubMedGoogle Scholar
  18. 18.
    Faulx MD, Ernsberger P, Vatner D, Hoffman RD, Lewis W, Strachan R, Hoit BD (2005) Strain-dependent beta-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice. Am J Physiol Heart Circ Physiol 289(1):H30–H36CrossRefPubMedGoogle Scholar
  19. 19.
    Li X, Zhang ZL, Wang HF (2017) Fusaric acid (fa) protects heart failure induced by isoproterenol (isp) in mice through fibrosis prevention via tgf-beta1/smads and pi3k/akt signaling pathways. Biomed Pharmacother 93:130–145CrossRefPubMedGoogle Scholar
  20. 20.
    Vergaro G, Prud’homme M, Fazal L, Merval R, Passino C, Emdin M, Samuel JL, Cohen Solal A, Delcayre C (2016) Inhibition of galectin-3 pathway prevents isoproterenol-induced left ventricular dysfunction and fibrosis in mice. Hypertension 67(3):606–612PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sunny C. Chang
    • 1
  • Shuxun Ren
    • 1
  • Christoph D. Rau
    • 1
  • Jessica J. Wang
    • 1
  1. 1.Division of Cardiology, Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA

Personalised recommendations