Growth hormone attenuates early left ventricular remodeling and improves cardiac function in rats with large myocardial infarction

Department of Medicine (Cardiovascular Division), Beth Israel Hospital, Boston, Massachusetts 02215, USA.

OBJECTIVES: We sought to investigate the cardiac effects of growth hormone (GH) administration during the early phase of pathologic remodeling in a rat model of large myocardial infarction (MI). BACKGROUND: Recent evidence suggests that exogenous administration of GH evokes a hypertrophic response and increases left ventricular (LV) function in vivo in rats with normal or chronically failing hearts. We hypothesized that these effects would attenuate ventricular remodeling early after MI. METHODS: Fifty-eight male rats underwent sham operation (n = 19) or had induced MI (n = 39). The day after the operation, the infarcted rats were randomized to receive 3 weeks of treatment with GH, 3 mg/kg body weight per day (n = 19) or placebo (n = 20). Echocardiography, catheterization and isolated whole heart preparations were used to define cardiac structure and function. RESULTS: Growth hormone caused hypertrophy of the noninfarcted myocardium in a concentric pattern, as noted by higher echocardiographic relative wall thickness at 3 weeks and by morphometric histologic examination. Left ventricular dilation was reduced in the GH-treated versus placebo group (echocardiographic LV diastolic diameter to body weight ratio 2.9 +/- 0.1 vs. 3.5 +/- 0.2 cm/kg; p < 0.05). In vivo and in vitro cardiac function was improved after GH treatment. Despite elevated insulin-like growth factor-1 (IGF-1) serum levels in GH-treated rats, myocardial IGF-I messenger ribonucleic acid was not different among the three groups, suggesting that an increase in its local expression does not appear necessary to yield the observed effects. CONCLUSIONS: These data demonstrate that early treatment of large MI with GH attenuates the early pathologic LV remodeling and improves LV function.

This article has been cited by other articles:

				S. Fukui, S. Kitagawa-Sakakida, S. Kawamata, G. Matsumiya, N. Kawaguchi, N. Matsuura, and Y. Sawa Therapeutic Effect of Midkine on Cardiac Remodeling in Infarcted Rat Hearts Ann. Thorac. Surg., February 1, 2008; 85(2): 562 - 570. [Abstract] [Full Text] [PDF]

				S. Fazio, E. A. Palmieri, F. Affuso, A. Cittadini, G. Castellano, T. Russo, A. Ruvolo, R. Napoli, and L. Sacca Effects of Growth Hormone on Exercise Capacity and Cardiopulmonary Performance in Patients with Chronic Heart Failure J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4218 - 4223. [Abstract] [Full Text] [PDF]

				P. Le Corvoisier, L. Hittinger, P. Chanson, O. Montagne, I. Macquin-Mavier, and P. Maison Cardiac Effects of Growth Hormone Treatment in Chronic Heart Failure: A Meta-Analysis J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 180 - 185. [Abstract] [Full Text] [PDF]

				A. Baessler, A. E. Kwitek, M. Fischer, M. Koehler, W. Reinhard, J. Erdmann, G. Riegger, A. Doering, H. Schunkert, and C. Hengstenberg Association of the Ghrelin Receptor Gene Region With Left Ventricular Hypertrophy in the General Population: Results of the MONICA/KORA Augsburg Echocardiographic Substudy Hypertension, May 1, 2006; 47(5): 920 - 927. [Abstract] [Full Text] [PDF]

				N. S. Dhalla, M. R. Dent, P. S. Tappia, R. Sethi, J. Barta, and R. K. Goyal Subcellular Remodeling as a Viable Target for the Treatment of Congestive Heart Failure Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 31 - 45. [Abstract] [PDF]

				L. Groban, N. A. Pailes, C. D. L. Bennett, C. S. Carter, M. C. Chappell, D. W. Kitzman, and W. E. Sonntag Growth Hormone Replacement Attenuates Diastolic Dysfunction and Cardiac Angiotensin II Expression in Senescent Rats J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2006; 61(1): 28 - 35. [Abstract] [Full Text] [PDF]

				S. Marleau, M. Mulumba, D. Lamontagne, and H. Ong Cardiac and peripheral actions of growth hormone and its releasing peptides: Relevance for the treatment of cardiomyopathies Cardiovasc Res, January 1, 2006; 69(1): 26 - 35. [Abstract] [Full Text] [PDF]

				J. K. Larsen, C.-C. Chen, and P. M. Best Disruption of growth hormone secretion alters Ca2+ current density and expression of Ca2+ channel and insulin-like growth factor genes in rat atria Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H829 - H838. [Abstract] [Full Text] [PDF]

				N. Nagaya, J. Moriya, Y. Yasumura, M. Uematsu, F. Ono, W. Shimizu, K. Ueno, M. Kitakaze, K. Miyatake, and K. Kangawa Effects of Ghrelin Administration on Left Ventricular Function, Exercise Capacity, and Muscle Wasting in Patients With Chronic Heart Failure Circulation, December 14, 2004; 110(24): 3674 - 3679. [Abstract] [Full Text] [PDF]

				T. Henriques-Coelho, J. Correia-Pinto, R. Roncon-Albuquerque Jr, M. J. Baptista, A. P. Lourenco, S. M. Oliveira, A. Brandao-Nogueira, A. Teles, J. M. Fortunato, and A. F. Leite-Moreira Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2885 - H2890. [Abstract] [Full Text] [PDF]

				K. Komamura, R. Tatsumi, J.-i. Miyazaki, K. Matsumoto, E. Yamato, T. Nakamura, Y. Shimizu, T. Nakatani, S. Kitamura, H. Tomoike, et al. Treatment of Dilated Cardiomyopathy With Electroporation of Hepatocyte Growth Factor Gene Into Skeletal Muscle Hypertension, September 1, 2004; 44(3): 365 - 371. [Abstract] [Full Text] [PDF]

				A. Cittadini, J.o. Isgaard, M. G. Monti, C. Casaburi, A. Di Gianni, R. Serpico, G. Iaccarino, and L. Sacca Growth hormone prolongs survival in experimental postinfarction heart failure J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2154 - 2163. [Abstract] [Full Text] [PDF]

				A. Cittadini, M. G. Monti, J. Isgaard, C. Casaburi, H. Stromer, A. Di Gianni, R. Serpico, L. Saldamarco, M. Vanasia, and L. Sacca Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure Cardiovasc Res, June 1, 2003; 58(3): 555 - 564. [Abstract] [Full Text] [PDF]

				A. Cittadini, L. Ines Comi, S. Longobardi, V. Rocco Petretta, C. Casaburi, L. Passamano, B. Merola, E. Durante-Mangoni, L. Sacca, and L. Politano A preliminary randomized study of growth hormone administration in Becker and Duchenne muscular dystrophies Eur. Heart J., April 1, 2003; 24(7): 664 - 672. [Abstract] [Full Text] [PDF]

				S. Marleau, N. Lapointe, J. Massicotte, C. Cemeus, G. Jasmin, L. Dumont, M. G. Sirois, J.-L. Rouleau, P. du Souich, and H. Ong Effect of Chronic Treatment with Bovine Recombinant Growth Hormone on Cardiac Dysfunction and Lesion Progression in UM-X7.1 Cardiomyopathic Hamsters Endocrinology, December 1, 2002; 143(12): 4846 - 4855. [Abstract] [Full Text] [PDF]

				M. Jain, R. Liao, B. K. Podesser, S. Ngoy, C. S. Apstein, and F. R. Eberli Influence of gender on the response to hemodynamic overload after myocardial infarction Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2544 - H2550. [Abstract] [Full Text] [PDF]

				J.-Y. Min, Y. Yang, K. L. Converso, L. Liu, Q. Huang, J. P. Morgan, and Y.-F. Xiao Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats J Appl Physiol, January 1, 2002; 92(1): 288 - 296. [Abstract] [Full Text] [PDF]

				I. Pagel, T. Langenickel, K. Hohnel, S. Philipp, A. K. Nussler, W. F. Blum, M. L. Aubert, R. Dietz, and R. Willenbrock Cardiac and Renal Effects of Growth Hormone in Volume Overload-Induced Heart Failure: Role of NO Hypertension, January 1, 2002; 39(1): 57 - 62. [Abstract] [Full Text] [PDF]

				M.-W. Hwang, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, M. Hara, T. Miyamoto, M. Touma, and S. Sasayama Neutralization of interleukin-1{beta} in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1546 - 1553. [Abstract] [Full Text] [PDF]

				J. W. A. Smit, Y. J. H. Janssen, H. J. Lamb, E. E. van der Wall, M. P. M. Stokkel, E. Viergever, N. R. Biermasz, J. J. Bax, H. W. Vliegen, A. de Roos, et al. Six Months of Recombinant Human GH Therapy in Patients with Ischemic Cardiac Failure Does Not Influence Left Ventricular Function and Mass J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4638 - 4643. [Abstract] [Full Text] [PDF]

				N. Nagaya, M. Uematsu, M. Kojima, Y. Ikeda, F. Yoshihara, W. Shimizu, H. Hosoda, Y. Hirota, H. Ishida, H. Mori, et al. Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure Circulation, September 18, 2001; 104(12): 1430 - 1435. [Abstract] [Full Text] [PDF]

				T. Wannenburg, A. S. Khan, D. C. Sane, M. C. Willingham, T. Faucette, and W. E. Sonntag Growth hormone reverses age-related cardiac myofilament dysfunction in rats Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H915 - H922. [Abstract] [Full Text] [PDF]

				M. Palmen, M.J.A.P. Daemen, R. Bronsaer, W.R.M. Dassen, H.R. Zandbergen, M. Kockx, J.F.M. Smits, R. van der Zee, and P.A. Doevendans Cardiac remodeling after myocardial infarction is impaired in IGF-1 deficient mice Cardiovasc Res, June 1, 2001; 50(3): 516 - 524. [Abstract] [Full Text] [PDF]

				A. Cittadini, J. D. Grossman, H. Stromer, S. E. Katz, J. P. Morgan, and P. S. Douglas Importance of an Intact Growth Hormone/Insulin-Like Growth Factor 1 Axis for Normal Post-Infarction Healing: Studies in Dwarf Rats Endocrinology, January 1, 2001; 142(1): 332 - 338. [Abstract] [Full Text] [PDF]

				E. Omerovic, E. Bollano, R. Mobini, V. Kujacic, B. Madhu, B. Soussi, M. Fu, A. Hjalmarson, F. Waagstein, and J. Isgaard Growth Hormone Improves Bioenergetics and Decreases Catecholamines in Postinfarct Rat Hearts Endocrinology, December 1, 2000; 141(12): 4592 - 4599. [Abstract] [Full Text] [PDF]

				F. Weekers, E. Van Herck, J. Isgaard, and G. Van den Berghe Pretreatment with Growth Hormone-Releasing Peptide-2 Directly Protects against the Diastolic Dysfunction of Myocardial Stunning in an Isolated, Blood-Perfused Rabbit Heart Model Endocrinology, November 1, 2000; 141(11): 3993 - 3999. [Abstract] [Full Text] [PDF]

				K.C. Wollert and H. Drexler Growth hormone and insulin-like growth factor--friends of the infarcted heart? Eur. Heart J., September 2, 2000; 21(18): 1499 - 1501. [PDF]

				L Friberg, S Werner, G Eggertsen, and S Ahnve Growth hormone and insulin-like growth factor-1 in acute myocardial infarction Eur. Heart J., September 2, 2000; 21(18): 1547 - 1554. [Abstract] [PDF]

				Y. Iwanaga, Y. Kihara, T. Yoneda, T. Aoyama, and S. Sasayama Modulation of in vivo cardiac hypertrophy with insulin-like growth factor-1 and angiotensin-converting enzyme inhibitor: relationship between change in myosin isoform and progression of left ventricular dysfunction J. Am. Coll. Cardiol., August 1, 2000; 36(2): 635 - 642. [Abstract] [Full Text] [PDF]

				K. J. Osterziel, W. F. Blum, O. Strohm, and R. Dietz The Severity of Chronic Heart Failure due to Coronary Artery Disease Predicts the Endocrine Effects of Short- Term Growth Hormone Administration J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1533 - 1539. [Abstract] [Full Text]

				A. Tivesten, E. Bollano, K. Caidahl, V. Kujacic, X. Y. Sun, T. Hedner, A. Hjalmarson, B.-A. Bengtsson, and J. Isgaard The Growth Hormone Secretagogue Hexarelin Improves Cardiac Function in Rats after Experimental Myocardial Infarction Endocrinology, January 1, 2000; 141(1): 60 - 66. [Abstract] [Full Text] [PDF]

				S. Fazio, A. Cittadini, B. Biondi, E. A. Palmieri, G. Riccio, F. Bonè, U. Oliviero, and L. Saccà Cardiovascular Effects of Short-Term Growth Hormone Hypersecretion J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 179 - 182. [Abstract] [Full Text]

				V Gersl, J Cerman, P Suba, Y Mazurova, R Hrdina, and J Machackova IGF-I in experimental daunorubicin-induced cardiomyopathy in rabbits Human and Experimental Toxicology, March 1, 1999; 18(3): 154 - 161. [Abstract] [PDF]

				D. J. Ing, J. Zang, V. J. Dzau, K. A. Webster, and N. H. Bishopric Modulation of Cytokine-Induced Cardiac Myocyte Apoptosis by Nitric Oxide, Bak, and Bcl-x Circ. Res., January 22, 1999; 84(1): 21 - 33. [Abstract] [Full Text] [PDF]

				J. Ross Jr Growth Hormone, Cardiomyocyte Contractile Reserve, and Heart Failure Circulation, January 12, 1999; 99(1): 15 - 17. [Full Text] [PDF]

				S. Genth-Zotz, R. Zotz, S. Geil, T. Voigtlander, J. Meyer, and H. Darius Recombinant Growth Hormone Therapy in Patients With Ischemic Cardiomyopathy : Effects on Hemodynamics, Left Ventricular Function, and Cardiopulmonary Exercise Capacity Circulation, January 12, 1999; 99(1): 18 - 21. [Abstract] [Full Text] [PDF]

				M. Tajima, E. O. Weinberg, J. Bartunek, H. Jin, R. Yang, N. F. Paoni, and B. H. Lorell Treatment With Growth Hormone Enhances Contractile Reserve and Intracellular Calcium Transients in Myocytes From Rats With Postinfarction Heart Failure Circulation, January 12, 1999; 99(1): 127 - 134. [Abstract] [Full Text] [PDF]

				D. Grimm, D. Cameron, D. P. Griese, G. A.J. Riegger, and E. P. Kromer Differential effects of growth hormone on cardiomyocyte and extracellular matrix protein remodeling following experimental myocardial infarction Cardiovasc Res, November 1, 1998; 40(2): 297 - 306. [Abstract] [Full Text] [PDF]

				A. Cittadini, Y. Ishiguro, H. Stromer, M. Spindler, A. C. Moses, R. Clark, P. S. Douglas, J. S. Ingwall, and J. P. Morgan Insulin-like Growth Factor-1 but Not Growth Hormone Augments Mammalian Myocardial Contractility by Sensitizing the Myofilament to Ca2+ Through a Wortmannin-Sensitive Pathway : Studies in Rat and Ferret Isolated Muscles Circ. Res., June 13, 1998; 83(1): 50 - 59. [Abstract] [Full Text] [PDF]

				A. Cittadini, H. Stromer, D. E. Vatner, J. D. Grossman, S. E. Katz, R. Clark, J. P. Morgan, and P. S. Douglas Consequences of Growth Hormone Deficiency on Cardiac Structure, Function, and {beta}-Adrenergic Pathway: Studies in Mutant Dwarf Rats Endocrinology, December 1, 1997; 138(12): 5161 - 5169. [Abstract] [Full Text] [PDF]

				L. Sacca Growth hormone: a newcomer in cardiovascular medicine Cardiovasc Res, October 1, 1997; 36(1): 3 - 9. [Full Text] [PDF]

				C. Lu, G. Schwartzbauer, M. A. Sperling, S. U. Devaskar, S. Thamotharan, P. D. Robbins, C. F. McTiernan, J.-L. Liu, J. Jiang, S. J. Frank, et al. Demonstration of Direct Effects of Growth Hormone on Neonatal Cardiomyocytes J. Biol. Chem., June 15, 2001; 276(25): 22892 - 22900. [Abstract] [Full Text] [PDF]