Experimental Model for Heart Failure in Rats - Induction and Diagnosis

Abstract

Background: Clinical heart failure is generally preceded by hypertrophy. Many animal models (e. g. toxic heart failure models) do not consider this hypertrophy. We set out to develop a heart failure model in rats by inducing pressure-overload hypertrophy. Methods: We induced coarctation of the aortic arch with a tantalum clip (0.35 mm internal diameter) In 3-week-old rats (n = 17). Starting at seven weeks postoperatively, we measured ejection fraction (EF), fractional shortening (FS), end-systolic (LVESD) and end-diastolic (LVEDD) left ventricular dimensions by echocardiography each week. Heart, lung, and liver specimens were analyzed histopathologically at least eleven weeks after the operation. Results: Contractile function was significantly decreased in hearts from animals with aortic banding (EF: 45 ± 5 % vs. 73 ± 5 %, p < 0.01; FS: 20 ± 3 % vs. 35 ± 5 %, p < 0.01). At the same time, left ventricles were dilated (LVEDD: 9.1 ± 0.6 mm vs. 7.4 ± 0.5 mm; LVESD: 7.3 ± 0.6 mm vs. 4.8 ± 0.4 mm, p < 0.01). These observations were associated with clinical and histopathological changes characteristic for chronic left heart failure. Conclusion: Placing a tantalum clip around the aortic arch in 3-week-old rats consistently induces left ventricular decrease in contractile function and dilatation after eleven weeks.

Echocardiography - heart failure - congestive - hypertrophy - myocardium

References

• 1 World Health Organisation .The World Health Report 1999 - Making a difference. Available from http://www.who.int/whr/1999. 
• 2 Osler W. The Principles and Practice of Medicine. New York, NY; Appleton & Co 1892
• 3 Stumpe K O, Solle H, Klein H, Kruck F. Mechanism of sodium and water retention in rats with experimental heart failure.  Kidney Int. 1973;  4 309-317
• 4 Mettler F P, Young D M, Ward J M. Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats.  Cancer Res. 1977;  37 2705-2713
• 5 Feldman A M, Weinberg E O, Ray P E, Lorell B H. Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding.  Circ Res. 1993;  73 184-192
• 6 Litwin S E, Katz S E, Morgan J P, Douglas P S. Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat.  Circulation. 1994;  89 345-354
• 7 MacLellan W R, Schneider M D. Success in failure: modeling cardiac decompensation in transgenic mice.  Circulation. 1998;  97 1433-1435
• 8 Esposito G, Rapacciuolo A, Naga Prasad S V. et al . Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress.  Circulation. 2002;  105 85-92
• 9 Sahn D J, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.  Circulation. 1978;  58 1072-1083
• 10 Zar J H. Biostatistical Analysis. 4 ed. Upper Saddle River: Prentice-Hall, Inc 1999
• 11 Litwin S E, Katz S E, Weinberg E O. et al . Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure.  Circulation. 1995;  91 2642-2654
• 12 Rockman H A, Ross R S, Harris A N. et al . Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.  Proc Natl Acad Sci USA. 1991;  88 8277-8281
• 13 Liao Y, Ishikura F, Beppu S. et al . Echocardiographic assessment of LV hypertrophy and function in aortic-banded mice: necropsy validation.  Am J Physiol Heart Circ Physiol. 2002;  282 H1703-H1708
• 14 Meguro T, Hong C, Asai K. et al . Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure.  Circ Res. 1999;  84 735-740
• 15 Del Monte F, Butler K, Boecker W, Gwathmey J K, Hajjar R J. Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure.  Physiol Genomics. 2002;  9 49-56
• 16 Guzman R J, Lemarchand P, Crystal R G, Epstein S E, Finkel T. Efficient gene transfer into myocardium by direct injection of adenovirus vectors.  Circ Res. 1993;  73 1202-1207
• 17 Desjardins S, Mueller R W, Cauchy M J. A pressure overload model of congestive heart failure in rats.  Cardiovasc Res. 1988;  22 696-702