{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:41:55Z","timestamp":1760236915458,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone\/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.<\/jats:p>","DOI":"10.3390\/ijms21030918","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T05:55:46Z","timestamp":1580450146000},"page":"918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction"],"prefix":"10.3390","volume":"21","author":[{"given":"Konstantinos V.","family":"Stamatis","sequence":"first","affiliation":[{"name":"1st Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianthi","family":"Kontonika","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos P.","family":"Daskalopoulos","sequence":"additional","affiliation":[{"name":"Pole of Cardiovascular Research, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-9131","authenticated-orcid":false,"given":"Theofilos M.","family":"Kolettis","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, University Hospital of Ioannina, 45500 Ioannina, Greece"},{"name":"Cardiovascular Research Institute, 45500 Ioannina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kibos, A.S., Knight, B.P., Essebag, V., Fishberger, S.B., Slevin, M., and Tintoiu, I.C. (2014). Ventricular arrhythmias during acute ischemia\/infarction: Mechanisms and management. Cardiac Arrhythmias: From Basic Mechanism to State-of-the-Art Management, Springer-Verlag.","DOI":"10.1007\/978-1-4471-5316-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.coph.2013.01.001","article-title":"Coronary artery disease and ventricular tachyarrhythmia: Pathophysiology and treatment","volume":"13","author":"Kolettis","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3181\/00379727-93-22749","article-title":"Chromatographic separation of growth hormone and other peptides","volume":"93","author":"Raben","year":"1956","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9905","DOI":"10.1016\/S0021-9258(18)81745-8","article-title":"Regulation of rat growth hormone receptor gene expression","volume":"264","author":"Mathews","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4137\/CMED.S38201","article-title":"Multiple effects of growth hormone in the body: Is it really the hormone for growth?","volume":"9","author":"Devesa","year":"2016","journal-title":"Clin. Med. Insights Endocrinol. Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.mehy.2004.07.028","article-title":"Early, selective growth hormone administration may ameliorate left ventricular remodeling after myocardial infarction","volume":"64","author":"Mitsi","year":"2005","journal-title":"Med. Hypotheses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e618","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth universal definition of myocardial infarction (2018)","volume":"138","author":"Thygesen","year":"2018","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1093\/eurheartj\/ehl218","article-title":"Risk factors for primary ventricular fibrillation during acute myocardial infarction: A systematic review and meta-analysis","volume":"27","author":"Gheeraert","year":"2006","journal-title":"Eur. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/sj.bjp.0706231","article-title":"Phase 2 ventricular arrhythmias in acute myocardial infarction: A neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation","volume":"145","author":"Hearse","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.amjmed.2008.04.024","article-title":"Early sustained ventricular arrhythmias complicating acute myocardial infarction","volume":"121","author":"Piccini","year":"2008","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1536\/ihj.31.845","article-title":"Bivalent effects of human growth hormone in experimental myocardial infarcts. Protective when administered alone and aggravating when combined with beta blockers","volume":"31","author":"Castagnino","year":"1990","journal-title":"Jpn. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/00005344-200002000-00015","article-title":"Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism","volume":"35","author":"Otani","year":"2000","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1161\/01.CIR.92.2.253","article-title":"Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats","volume":"92","author":"Opitz","year":"1995","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/CS20060193","article-title":"Growth hormone decreases phase II ventricular tachyarrhythmias during acute myocardial infarction in rats","volume":"112","author":"Elaiopoulos","year":"2007","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jelectrocard.2007.09.002","article-title":"Antiarrhythmic effects of growth hormone\u2014In vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology","volume":"41","author":"Gizurarson","year":"2008","journal-title":"J. Electrocardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/europace\/eum196","article-title":"Comparative effects of acute vs. chronic oral amiodarone treatment during acute myocardial infarction in rats","volume":"9","author":"Kolettis","year":"2007","journal-title":"Europace"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jelectrocard.2008.11.006","article-title":"Antiarrhythmic actions of growth hormone during acute myocardial infarction","volume":"42","author":"Elaiopoulos","year":"2009","journal-title":"J. Electrocardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1210\/endo.140.12.7209","article-title":"Activation of growth hormone receptor delivers an antiapoptotic signal: Evidence for a role of Akt in this pathway","volume":"140","author":"Costoya","year":"1999","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S1096-6374(02)00042-4","article-title":"Effects of early treatment with growth hormone on infarct size, survival, and cardiac gene expression after acute myocardial infarction","volume":"12","author":"Jin","year":"2002","journal-title":"Growth Horm. IGF Res."},{"key":"ref_20","first-page":"391","article-title":"Cytoprotection by melatonin and growth hormone in early rat myocardial infarction as revealed by Feulgen DNA staining","volume":"23","author":"Castagnino","year":"2002","journal-title":"Neuro. Endocrinol. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ghir.2007.08.002","article-title":"Randomised comparison of growth hormone versus IGF-1 on early post-myocardial infarction ventricular remodelling in rats","volume":"18","author":"Hatzistergos","year":"2008","journal-title":"Growth Horm. IGF Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1161\/01.CIR.56.5.786","article-title":"The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs","volume":"56","author":"Reimer","year":"1977","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/S0735-1097(03)00483-2","article-title":"Growth hormone prolongs survival in experimental postinfarction heart failure","volume":"41","author":"Cittadini","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Masternak, M.M., and Bartke, A. (2012). Growth hormone, inflammation and aging. Pathobiol. Aging Age Relat. Dis., 2.","DOI":"10.3402\/pba.v2i0.17293"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nrcardio.2014.28","article-title":"The inflammatory response in myocardial injury, repair, and remodelling","volume":"11","author":"Frangogiannis","year":"2014","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jelectrocard.2016.10.004","article-title":"Intra-myocardial growth hormone administration ameliorates arrhythmogenesis during ischemia-reperfusion in rats","volume":"50","author":"Kontonika","year":"2017","journal-title":"J. Electrocardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1515\/jbcpp-2013-0117","article-title":"Arrhythmogenesis after acute myocardial necrosis with and without preceding ischemia in rats","volume":"25","author":"Kolettis","year":"2014","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1046\/j.1365-2265.2002.01546.x","article-title":"Sympathetic nerve hyperactivity is associated with increased peripheral vascular resistance in hypopituitary patients with growth hormone deficiency","volume":"56","author":"Scott","year":"2002","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"ref_29","first-page":"1881","article-title":"Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency","volume":"83","author":"Elam","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1210\/endo.141.12.7803","article-title":"Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts","volume":"141","author":"Omerovic","year":"2000","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/00005344-198806121-00002","article-title":"Adrenergic mechanisms in myocardial infarction: Cardiac and systemic catecholamine release","volume":"12","year":"1988","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1515\/JBCPP.1993.4.4.335","article-title":"High arrythmogenesis during early reperfusion of ischaemic myocardium: Participation of oxygen free radicals","volume":"4","author":"Ravingerova","year":"1993","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/eurheartj\/12.suppl_F.38","article-title":"Catecholamine release and arrhythmias in acute myocardial ischaemia","volume":"12","author":"Haass","year":"1991","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00169296","article-title":"Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts","volume":"349","author":"Rump","year":"1994","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.2174\/138161282012140401153832","article-title":"Novel strategies for cardiac repair post-myocardial infarction","volume":"20","author":"Agathopoulos","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1161\/01.CIR.101.25.2981","article-title":"Left ventricular remodeling after myocardial infarction: Pathophysiology and therapy","volume":"101","author":"Sutton","year":"2000","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1053\/euhj.2000.2125","article-title":"Growth hormone and insulin-like growth factor-1 in acute myocardial infarction","volume":"21","author":"Friberg","year":"2000","journal-title":"Eur. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1172\/JCI119730","article-title":"Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy","volume":"100","author":"Li","year":"1997","journal-title":"J. Clin. Invest."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0735-1097(97)00010-7","article-title":"Growth hormone attenuates early left ventricular remodeling and improves cardiac function in rats with large myocardial infarction","volume":"29","author":"Cittadini","year":"1997","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3109\/08977194.2015.1072527","article-title":"Attenuation of post-infarction remodeling in rats by sustained myocardial growth hormone administration","volume":"33","author":"Daskalopoulos","year":"2015","journal-title":"Growth Factors"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.2174\/1381612824666180629162726","article-title":"Microvasculature recovery by angiogenesis after myocardial infarction","volume":"24","author":"Badimon","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.yjmcc.2013.11.015","article-title":"Fibroblasts in myocardial infarction: A role in inflammation and repair","volume":"70","author":"Shinde","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ghir.2006.02.001","article-title":"Early, intracoronary growth hormone administration attenuates ventricular remodeling in a porcine model of myocardial infarction","volume":"16","author":"Mitsi","year":"2006","journal-title":"Growth Horm. IGF Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/CIRCINTERVENTIONS.110.960765","article-title":"Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction","volume":"4","author":"Leblond","year":"2011","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ahj.2018.03.018","article-title":"Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)","volume":"200","author":"Caplice","year":"2018","journal-title":"Am. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08977194.2017.1297432","article-title":"Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats","volume":"35","author":"Kontonika","year":"2017","journal-title":"Growth Factors"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1369\/0022155413493912","article-title":"Systematic characterization of myocardial inflammation, repair, and remodeling in a mouse model of reperfused myocardial infarction","volume":"61","author":"Christia","year":"2013","journal-title":"J. Histochem. Cytochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1161\/01.RES.72.1.57","article-title":"Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion","volume":"72","author":"Mayoux","year":"1993","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1172\/JCI114737","article-title":"Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle","volume":"86","author":"Timsit","year":"1990","journal-title":"J. Clin. Invest."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0008-6363(98)00095-9","article-title":"Growth hormone preserves cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors) and enhances cardiac function in cardiomyopathic hamsters","volume":"40","author":"Ueyama","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0008-6363(98)00181-3","article-title":"Differential effects of growth hormone on cardiomyocyte and extracellular matrix protein remodeling following experimental myocardial infarction","volume":"40","author":"Grimm","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1054\/ghir.1999.0097","article-title":"The effect of growth hormone on rat myocardial collagen","volume":"9","author":"Oxlund","year":"1999","journal-title":"Growth Horm. IGF Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0008-6363(99)00068-1","article-title":"Does growth hormone reduce fibrosis?","volume":"43","author":"Beranek","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.2174\/13816128113199990452","article-title":"Cardiac (myo)fibroblast: Novel strategies for its targeting following myocardial infarction","volume":"20","author":"Daskalopoulos","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1097\/FJC.0b013e31820cda19","article-title":"The cardiac fibroblast: Functional and electrophysiological considerations in healthy and diseased hearts","volume":"57","author":"Vasquez","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1161\/01.CIR.101.10.1172","article-title":"The cardiac Fas(APO-1\/CD95)receptor\/Fas ligand system: Relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes","volume":"101","author":"Wollert","year":"2000","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1172\/JCI13779","article-title":"Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload","volume":"109","author":"Badorff","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_58","first-page":"H445","article-title":"Expression of FAS adjacent to fibrotic foci in the failing human heart is not associated with increased apoptosis","volume":"277","author":"Filippatos","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.mce.2003.12.004","article-title":"GH suppresses TGF-beta-mediated fibrosis and retains cardiac diastolic function","volume":"218","author":"Imanishi","year":"2004","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1006\/excr.1996.0232","article-title":"Programmed myocyte cell death affects the viable myocardium after infarction in rats","volume":"226","author":"Cheng","year":"1996","journal-title":"Exp. Cell. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1161\/01.CIR.99.1.18","article-title":"Recombinant growth hormone therapy in patients with ischemic cardiomyopathy: Effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity","volume":"99","author":"Zotz","year":"1999","journal-title":"Circulation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1053\/euhj.1998.1123","article-title":"A placebo-controlled study of growth hormone in patients with congestive heart failure","volume":"19","author":"Isgaard","year":"1998","journal-title":"Eur. Heart J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/S0140-6736(97)11329-0","article-title":"Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy","volume":"351","author":"Osterziel","year":"1998","journal-title":"Lancet"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1210\/jc.2009-0533","article-title":"Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction","volume":"94","author":"Cittadini","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jchf.2013.04.003","article-title":"Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency: An extension of a randomized controlled single-blind study","volume":"1","author":"Cittadini","year":"2013","journal-title":"JACC Heart Fail."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/jbm.b.34113","article-title":"Optimization of Ca(2+) content in alginate hydrogel injected in myocardium","volume":"107","author":"Barka","year":"2019","journal-title":"J. Biomed. Mater. Res. B Appl. Biomater."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/918\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:18Z","timestamp":1760172798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/3\/918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,30]]},"references-count":66,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["ijms21030918"],"URL":"https:\/\/doi.org\/10.3390\/ijms21030918","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,1,30]]}}}