Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-27T22:57:13.338Z Has data issue: false hasContentIssue false

The effects of basic fibroblast growth factor in an animal model of acute mechanically induced right ventricular hypertrophy

Published online by Cambridge University Press:  27 January 2012

Vladimiro L. Vida*
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Padua, Italy
Arben Dedja
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Padua, Italy
Elisabetta Faggin
Affiliation:
Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
Simone Speggiorin
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Padua, Italy
Massimo A. Padalino
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Padua, Italy
Giovanna Boccuzzo
Affiliation:
Department of Statistics, University of Padua, Padua, Italy
Paolo Pauletto
Affiliation:
Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
Annalisa Angelini
Affiliation:
Department of Medical Diagnostic Sciences and Special Therapies, University of Padua, Padua, Italy
Ornella Milanesi
Affiliation:
Department of Paediatric Cardiology, University of Padua, Padua, Italy
Gaetano Thiene
Affiliation:
Department of Medical Diagnostic Sciences and Special Therapies, University of Padua, Padua, Italy
Giovanni Stellin
Affiliation:
Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Padua, Italy
*
Correspondence to: Dr V. L. Vida, MD, PhD, Department of Paediatric and Congenital Cardiac Surgery Unit, University of Padua, Via Giustiniani, 2-35128 Padua, Italy. Tel: +39 049 8212410; Fax: +39 049 8212409; E-mail: [email protected]

Abstract

Objective

To evaluate the effect of a continuous infusion of basic fibroblast growth factor on the adaptive potential of the right ventricular myocardium after 30 days of mechanically induced overload in rats.

Materials and methods

We banded the pulmonary trunk, so as to increase the systolic workload of the right ventricle, in six Lewis/HanHsd rats at the age of 11 weeks, using six adult rats as controls. The six adult rats were also banded and received an additional continuous infusion of basic fibroblastic growth factor, using six rats with a continuous infusion of basic fibroblastic growth factor only as controls. We analysed the functional adaptation and structural changes of the right ventricular myocardium, blood vessels, and interstitial tissue 30 days after the increased afterload.

Results

The pulmonary artery banding induced an increase in the right ventricular free wall thickness of banded rats when compared with controls, which was mainly justified by an increase in cardiomyocyte area and in the percentage of extracellular fibrosis. The infusion of basic fibroblastic growth factor promotes a more extensive capillary network in banded rats (p < 0.001), which modulates the compensatory response of the right ventricle, promoting the hypertrophy of contractile elements and limiting the areas in which fibrosis develops (p < 0.001).

Conclusions

The subcutaneous infusion with osmotic pumps was a valid and reproducible method of delivering basic fibroblast growth factor to heart tissue. This infusion contributed to better preserve the right ventricular capillary network, hampering the development of interstitial fibrosis.

Type
Original Article
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Ross, J Jr, Franklin, D, Sasayama, S. Preload, afterload, and the role of afterload mismatch in the descending limb of cardiac function. Eur J Cardiol 1976 May; 4 Suppl., 7786.Google Scholar
2. Izumo, S, Nadal-Ginard, B, Mahdavi, V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 1988; 85: 339343.CrossRefGoogle ScholarPubMed
3. Litten, RZ III, Martin, BJ, Low, RB, Alpert, NR. Altered myosin isozyme patterns from pressure-overloaded and thyrotoxic hypertrophied rabbit hearts. Circ Res 1982; 50: 856864.CrossRefGoogle ScholarPubMed
4. Hornung, TS, Bernard, EJ, Jaeggi, ET, Howman-Giles, RB, Celermajer, DS, Hawker, RE. Myocardial perfusion defects and associated systemic ventricular dysfunction in congenitally corrected transposition of the great arteries. Heart 1998; 80: 322326.CrossRefGoogle ScholarPubMed
5. Di Salvo, G, Pacileo, G, Rea, A, et al. Transverse strain predicts exercise capacity in systemic right ventricle patients. Int J Cardiol 2010; 145: 193196.CrossRefGoogle ScholarPubMed
6. Lorenz, CH, Walker, ES, Graham, TP Jr, Powers, TA. Right ventricular performance and mass by use of cine MRI late after atrial repair of transposition of the great arteries. Circulation 1995; 92: II233II239.CrossRefGoogle ScholarPubMed
7. Vida, VL, Angelini, A, Ausoni, S, et al. Age is a risk factor for maladaptive changes in rats exposed to increased pressure loading of the right ventricular myocardium. Cardiol Young 2007; 17: 202211.CrossRefGoogle ScholarPubMed
8. Olivetti, G, Quaini, F, Lagrasta, C, et al. Cellular basis of ventricular remodeling after myocardial infarction in rats. Cardioscience 1995; 6: 101106.Google ScholarPubMed
9. Izumo, S, Nadal-Ginard, B, Mahdavi, V. Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 1988; 85: 339343.CrossRefGoogle ScholarPubMed
10. LekanneDeprez, RH, van den Hoff, MJ, de Boer, PA, et al. Changing patterns of gene expression in the pulmonary trunk-banded rat heart. J Mol Cell Cardiol 1998; 30: 18771888.CrossRefGoogle ScholarPubMed
11. Olivetti, G, Lagrasta, C, Ricci, R, Sonnenblick, EH, Capasso, JM, Anversa, P. Long-term pressure-induced cardiac hypertrophy: capillary and mast cell proliferation. Am J Physiol 1989; 257: H1766H1772.Google ScholarPubMed
12. Litten, RZ, Low, BJ, Alpert, NR. Altered myosin isozyme patterns from pressure overloaded and thyrotoxic hypertrophied rabbit hearts. Circ Res 1982; 50: 856864.CrossRefGoogle ScholarPubMed
13. Anversa, P, Palackal, T, Sonnenblick, EH, Olivetti, G, Meggs, LG, Capasso, JM. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rats. Circ Res 1990; 67: 871885.CrossRefGoogle Scholar
14. Olivetti, G, Quaini, F, Lagrasta, C, et al. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodelling in rats. Am J Pathol 1992; 141: 227239.Google ScholarPubMed
15. Boluyt, MO, O'Neill, L, Meredith, AL, et al. Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. Circ Res 1994; 75: 2332.CrossRefGoogle ScholarPubMed
16. Wong, K, Boheler, KR, Petrou, M, Yacoub, MH. Pharmacological modulation of pressure-overload cardiac hypertrophy. Changes in ventricular function, extracellular matrix and gene expression. Circulation 1997; 96: 22392246.CrossRefGoogle ScholarPubMed
17. Anderson, RH, Ho, SY, Redmann, K, Sanchez-Quintana, D, Lunkenheimer, PP. The anatomical arrangement of the myocardial cells making up the ventricular mass. Eur J Cardiothorac Surg 2005; 28: 517525.CrossRefGoogle ScholarPubMed
18. Lunkenheimer, PP, Redmann, K, Anderson, RH. Further discussions concerning the unique myocardial band. Eur J Cardiothorac Surg 2005; 28: 779780.CrossRefGoogle Scholar
19. Manabe, I, Shindo, T, Nagai, R. Gene expression in fibroblasts and fibrosis. Circ Res 2002; 91: 11031113.CrossRefGoogle ScholarPubMed
20. Harada, K, Komuro, I, Shiojima, I, et al. Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice. Circulation 1998; 97: 19521959.CrossRefGoogle ScholarPubMed
21. Laham, RJ, Rezaee, M, Post, M, Xu, X, Sellke, FW. Intrapericardial administration of basic fibroblast growth factor: myocardial and tissue distribution and comparison with intracoronary and intravenous administration. Catheter Cardiovasc Interv 2003; 58: 375381.CrossRefGoogle ScholarPubMed
22. Rakusan, K, du Mesnil de Rochemont, W, Braasch, W, Tschopp, H, Bing, RJ. Capacity of the terminal vascular bed during normal growth, in cardiomegaly, and in cardiac atrophy. Circ Res 1967; 21: 209215.CrossRefGoogle ScholarPubMed
23. Rakusan, K, Flanagan, MF, Geva, T, Southern, J, Van Praagh, R. Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure overload hypertrophy. Circulation 1992; 86: 3846.CrossRefGoogle ScholarPubMed
24. Friehs, I, Moran, AM, Stamm, C, et al. Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury. Ann Thorac Surg 2004; 77: 20042011.CrossRefGoogle ScholarPubMed
25. Detillieux, KA, Sheikh, F, Kardami, E, Cattini, PA. Biological activities of fibroblast growth factor-2 in the adult myocardium. Cardiovasc Res 2003; 57: 819.CrossRefGoogle ScholarPubMed
26. Garbern, JC, Minami, E, Stayton, PS, Murry, CE. Delivery of basic fibroblast growth factor with a pH-responsive, injectable hydrogel to improve angiogenesis in infarcted myocardium. Biomaterials 2011; 32: 24072416.CrossRefGoogle ScholarPubMed
27. Schultz, JE, Witt, SA, Nieman, ML, et al. Fibroblast growth factor-2 mediates pressure-induced hypertrophic response. J Clin Invest 1999; 104: 709719.CrossRefGoogle ScholarPubMed
28. Friehs, I, Moran, AM, Stamm, C, et al. Impaired glucose transporter activity in pressure overload hypertrophy is an early indicator of progression to failure. Circulation 1999; 100: II187II193.CrossRefGoogle ScholarPubMed
29. Ortega, S, Ittmann, M, Tsang, SH, Ehrlich, M, Basilico, C. Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2. Proc Natl Acad Sci USA 1998; 95: 56725677.CrossRefGoogle ScholarPubMed
30. Shao, ZQ, Takaji, K, Katayama, Y, et al. Effects of intramyocardial administration of slow-release basic fibroblast growth factor on angiogenesis and ventricular remodeling in a rat infarct model. Circ J 2006; 70: 471477.CrossRefGoogle Scholar
31. Wang, H, Zhang, X, Li, Y, et al. Improved myocardial performance in infarcted rat heart by co-injection of basic fibroblast growth factor with temperature-responsive chitosan hydrogel. J Heart Lung Transplant 2010; 29: 881887.CrossRefGoogle ScholarPubMed
32. Yajima, S, Ishikawa, M, Kubota, T, Moroi, M, Sugi, K, Namiki, A. Intramyocardial injection of fibroblast growth factor-2 plus heparin suppresses cardiac failure progression in rats with hypertensive heart disease. Int Heart J 2005; 46: 289301.CrossRefGoogle ScholarPubMed