Cardiomyopathic Syrian Hamster as a Model of Congestive Heart Failure

Sonia Goineau1, Sandra Picard1, Stéphane Hervé1, Pierre Lacroix1

1 Porsolt and Partners Pharmacology, Le Genest‐Saint‐Isle, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.50
DOI:  10.1002/0471141755.ph0550s42
Online Posting Date:  September, 2008
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Cardiomyopathic Syrian hamsters (Bio TO‐2 dilated strain) constitute an animal model of congestive heart failure, which progressively develops an alteration of cardiac function leading to decreased arterial blood pressure and musculo‐cutaneous blood flow associated with a complex process of cardiac remodeling including left ventricle dilation, wall thinning, and greater collagen density. The protocols described in this unit are designed to assess the pharmacological effects of new therapeutic strategies on cardiac and systemic hemodynamics, morphometry (body and target organs weight), cardiac remodeling (left ventricle dilation and collagen density), and survival in this model of dilated cardiomyopathy. Examples of results obtained with enalapril, an angiotensin I converting enzyme inhibitor, are provided for illustrative purposes. Curr. Protoc. Pharmacol. 42:5.50.1‐5.50.12. © 2008 by John Wiley & Sons, Inc.

Keywords: animal models; heart failure; hemodynamics; cardiac remodeling; survival

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Hemodynamic and Histomorphometric Investigation in Cardiomyopathic Syrian Hamsters
  • Basic Protocol 2: Survival Study in Cardiomyopathic Syrian Hamsters
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Hemodynamic and Histomorphometric Investigation in Cardiomyopathic Syrian Hamsters

  Materials
  • Cardiomyopathic (Bio TO‐2 dilated strain) male hamsters (Bio Breeders) at 115 days of age
  • Standard rodent diet [e.g., Scientific Animal and Food Engineering (SAFE), Code 113]
  • Vehicle or test substance
  • Distilled water (sterile water for injectable preparation, Laboratoire Aguettant)
  • Ketamine (Imalgène 1000; Virbac Santé Animale, http://www.virbac.fr/)
  • Xylazine (Rompun, Bayer)
  • Lubricating jelly (Fougera)
  • Sterile physiological saline (0.9% NaCl)
  • 10% formaldehyde solution
  • Paraffin
  • Gelling fluid
  • 1025‐cm2 polycarbonate cages
  • Animal balance accurate to 0.1 g (e.g., Sartorius)
  • Luer gastric probes with oval extremity for oral administration
  • 1‐ml syringe (e.g., Terumo type BS‐01‐T)
  • Needles (23‐G) for intraperitoneal administration of anesthetics
  • Tracheal cannula (polyethylene catheter; o.d. 1.27 mm, i.d. 0.86 mm)
  • Rodent respirator (Harvard Apparatus, Model 683)
  • 2F micromanometer‐tipped catheter, SPR407 (Millar Instruments)
  • Blood pressure recorder (e.g., Graphtec WR9000)
  • Surgical tools
  • Perivascular flow probe 1.5R (Transonic System)
  • Ultrasonic Flowmeter, model T206 Dual Channel (Transonic System)
  • Cassette (Histosette I, CML) which holds tissue specimen during the embedding process
  • Tissue processing machine (e.g., Leica, ASP300)
  • Stainless steel mold (e.g., CML, MI2430/9; http://www.cml.fr/)
  • Refrigerated plate
  • Microtome
  • Slide (CML, LR90D; http://www.cml.fr/)
  • Heating plate
  • Automatic staining machine (e.g., Microm, HMS760)
  • Glass coverslip (CML, LDS2460; http://www.cml.fr/)
  • Computer‐assisted image analyzer (Histolab and Saisam; Microvision Instruments, http://www.microvision.fr/index2.html)
  • Additional reagents and equipment for euthanasia of the animal by cervical dislocation and exsanguination (Donovan and Brown, )
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Bajusz, E., Baker, J.R., Nixon, C.W., and Homburger, F. 1969. Spontaneous hereditary myocardial degeneration and congestive heart failure in a strain of Syrian hamsters. Ann. N.Y. Acad. Sci. 156:105‐129.
   Bastien, N.R., Juneau, A.V., Ouellette, J., and Lambert, C. 1999. Chronic AT1 receptor blockade and angiotensin‐converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: Effects on cardiac hypertrophy and survival. Cardiovasc. Res. 43:77‐85.
   Bralet, J., Marie, C., Mossiat, C., Lecomte, J.M., Gros, C., and Schwartz, J.C. 1994. Effects of alatriopril, a mixed inhibitor of atriopeptidase and angiotensin I‐converting enzyme, on cardiac hypertrophy and hormonal responses in rats with myocardial infarction. Comparison with captopril. J. Pharmacol. Exp. Ther. 270:8‐14.
   Chemla, D., Scalbert, E., Desché, P., Lerebours, G., Suard, I., and Lecarpentier, Y. 1994. Effects of early and late therapy with perindopril on survival and myocardial inotropic state in experimental dilated cardiomyopathy. J. Cardiovasc. Pharmacol. 24:151‐157.
   Donovan, J. and Brown, P. 2006. Euthanasia. Curr. Protoc. Immunol. 73:1.8.1‐1.8.4.
   Gertz, E.W. 1972. Cardiomyopathic Syrian hamster: A possible model of human disease. Progr. Exp. Tumor. Res. 16:242‐260.
   Goineau, S., Pape, D., Guillo, P., Ramée, M.P., and Bellissant, E. 2001. Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of Syrian hamsters (Bio TO‐2 strain). Can. J. Physiol. Pharmacol. 79:329‐337.
   Goineau, S., Pape, D., Guillo, P., Ramée, M.P., and Bellissant, E. 2002a. Combined effects of metoprolol and spironolactone in dilated cardiomyopathic hamsters. J. Cardiovasc. Pharmacol. 40:543‐553.
   Goineau, S., Pape, D., Guillo, P., Ramée, M.P., and Bellissant, E. 2002b. Systemic and regional hemodynamic and cardiac remodeling effects of candesartan in dilated cardiomyopathic hamsters with advanced congestive heart failure. J. Cardiovasc. Pharmacol. 40:189‐200.
   Goineau, S., Pape, D., Guillo, P., Ramée, M.P., and Bellissant, E. 2003. Combined effects of enalapril and spironolactone in hamsters with dilated cardiomyopathy. J. Cardiovasc. Pharmacol. 41:49‐59.
   Haleen, S.J., Weishaar, R.E., Overhiser, R.W., Bousley, R.F., Keiser, J.A., Rapundalo, S.R., and Taylor, D.G. 1991. Effects of quinapril, a new angiotensin converting enzyme inhibitor, on left ventricular failure and survival in the cardiomyopathic hamster. Circ. Res. 68:1302‐1312.
   Hasenfuss, G. 1998. Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc. Res. 39:60‐76.
   Homburger F., Baker J.R., Nixon C.W., and Whitney R. 1962. Primary, generalized polymyopathy and cardiac necrosis in an inbred line of Syrian hamsters. Med. Exp. 6:339‐345.
   Hongo, M., Ryoke, T., and Ross, J. Jr. 1997. Animal models of heart failure. Recent developments and perspectives. Trends Cardiovasc. Med. 7:161‐167.
   Kaplan, E.L. and Meier, P. 1958. Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53:457–481.
   Nakamura, Y., Ryoke, T., Tanaka, N., Ohkusa, T., and Matsuzaki, M. 1998. Celiprolol, a β‐adrenoceptor antagonist with vasodilator effect, improves hemodynamic response to catecholamine, spontaneous locomotor activity, and survival in cardiomyopathic hamsters with advanced heart failure. J. Cardiovasc. Pharmacol. 31:171‐178.
   Narita, H., Kaburaki, M., Doi, H., Ogiku, N., Yabana, H., Kurosawa, H., and Ohmachi, Y. 1996. Prolonging action of imidapril on the lifespan expectancy of cardiomyopathic hamsters. J. Cardiovasc. Pharmacol. 27:861‐871.
   Panchal, B.C. and Trippodo, N.C. 1993. Systemic and regional haemodynamics in conscious Bio TO‐2 cardiomyopathic hamsters. Cardiovasc. Res. 27:2264‐2269.
   Pfeffer, M.A., Pfeffer, J.M., Fishbein, M.C., Fletcher, P.J., Spadaro, J., Kloner, R.A., and Braunwald E. 1979. Myocardial infarct size and ventricular function in rats. Circ. Res. 44:503‐512.
   Pfeffer, J.M., Pfeffer, M.A., and Braunwald, E. 1985. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ. Res. 57:84‐95.
   Ryoke, T., Gu, Y., Mao, L., Hongo, M., Clark, R.G., Peterson, K.L., and Ross, J. Jr. 1999. Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin‐converting enzyme inhibition. Circulation 100:1734‐1743.
   Sole, M.J. 1986. Hamster cardiomyopathy: Understanding the pathogenesis of heart failure. In Hamster Information Service: Bio‐Research Institute (F. Homburger, ed.) pp. 3‐6. Cambridge, Mass.
   Trippodo, N.C., Fox, M., Monticello, T.M., Panchal, B.C., and Asaad, M.M. 1999. Vasopeptidase inhibition with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril. J. Cardiovasc. Pharmacol. 34:782‐790.
   Ver Donck, L., Wouters, L., Olbrich, H.G., Mutschler, E., and Borgers, M. 1991. Nebivolol increases survival in cardiomyopathic hamsters with congestive heart failure. J. Cardiovasc. Pharmacol. 18:1‐3.
   Watanabe, M., Kawaguchi, H., Onozuka, H., Mikami, T., Urasawa, K., Okamoto, H., Watanabe, S., Abe, K., and Kitabatake, A. 1998. Chronic effects of enalapril and amlodipine on cardiac remodeling in cardiomyopathic hamster hearts. J. Cardiovasc. Pharmacol. 32:248‐259.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library