{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T06:13:42Z","timestamp":1764828822836,"version":"3.37.3"},"reference-count":57,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"name":"Mato Grosso State Research Support Foundation","award":["process 470627\/2011"],"award-info":[{"award-number":["process 470627\/2011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Sports Med"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Digoxin is a cardiotonic that increases the cardiac output without causing deleterious effects on heart, as well as improves the left ventricular performance during physical exercise. We tested whether the association between chronic digoxin administration and aerobic interval training (AIT) promotes beneficial cardiovascular adaptations by improving the myocardial contractility and calcium (Ca2+) handling. Male Wistar rats were randomly assigned to sedentary control (C), interval training (T), sedentary digoxin (DIGO) and T associated to digoxin (TDIGO). AIT was performed on a treadmill (1h\/day, 5 days\/week) for 60 days, consisting of successive 8-min periods at 80% and 20% of VO2m\u00e1x for 2 min. Digoxin was administered by orogastric gavage for 60 days. Left ventricle samples were collected to analysis of Ca2+ handling proteins; contractility and Ca2+ handling were performed on isolated cardiomyocytes. TDIGO group had a greater elevation in fractional shortening (44%) than DIGO, suggesting a cardiomyocyte contractile improvement. In addition, T or TDIGO groups showed no change in cardiomyocytes properties after Fura2-acetoxymethyl ester, as well as in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban and calcineurin expressions. The main findings indicate that association of digoxin and aerobic interval training improved the cardiomyocyte contractile function, but these effects seem to be unrelated to Ca2+ handling.<\/jats:p>","DOI":"10.1055\/a-1300-2583","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T23:42:37Z","timestamp":1608075757000},"page":"694-702","source":"Crossref","is-referenced-by-count":1,"title":["Digoxin Combined with Aerobic Interval Training Improved Cardiomyocyte Contractility"],"prefix":"10.1055","volume":"42","author":[{"given":"Gabriel Vasconcelos","family":"Abreu","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Science, Federal University of Mato Grosso, Sinop, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick Roberto Gon\u00e7alves","family":"Claudio","sequence":"additional","affiliation":[{"name":"Center of Physical Education and Sports, Department of Sports, Federal University of Esp\u00edrito Santo, Vit\u00f3ria, Esp\u00edrito Santo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreo Fernando","family":"Aguiar","sequence":"additional","affiliation":[{"name":"North University of Paran\u00e1 (UNOPAR), Centre of Research in Biological and Healthy Sciences, Londrina, Paran\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morenna Alana","family":"Giordani","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Science, Federal University of Mato Grosso, Sinop, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eveline Aparecida Isquierdo Fonseca","family":"de Queiroz","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Science, Federal University of Mato Grosso, Sinop, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Lima-Leopoldo","sequence":"additional","affiliation":[{"name":"Center of Physical Education and Sports, Department of Sports, Federal University of Esp\u00edrito Santo, Vit\u00f3ria, Esp\u00edrito Santo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5999-2671","authenticated-orcid":false,"given":"Andr\u00e9 Soares","family":"Leopoldo","sequence":"additional","affiliation":[{"name":"Center of Physical Education and Sports, Department of Sports, Federal University of Esp\u00edrito Santo, Vit\u00f3ria, Esp\u00edrito Santo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Mateus","family":"Sugizaki","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Science, Federal University of Mato Grosso, Sinop, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/IPRP.S133088","article-title":"Cardiovascular disease as a leading cause of death: How are pharmacists getting involved?","volume":"8","author":"K M Namara","year":"2019","journal-title":"Integr Pharm Res Pract"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1186\/s12889-019-7030-8","article-title":"The impact of physical activity and an additional behavioural risk factor on cardiovascular disease, cancer and all-cause mortality: A systematic review","volume":"19","author":"J Lacombe","year":"2019","journal-title":"BMC Public Health"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0008-6363(01)00210-3","article-title":"Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats","volume":"50","author":"U Wisl\u00f8ff","year":"2001","journal-title":"Cardiovasc Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10741-013-9373-z","article-title":"Calcium handling proteins: Structure, function, and modulation by exercise","volume":"19","author":"J Locatelli","year":"2014","journal-title":"Heart Fail Rev"},{"key":"ref5","first-page":"46","article-title":"Upregulation of mRNA myocardium calcium handling in rats submitted to exercise and food restriction","volume":"97","author":"M M Sugizaki","year":"2011","journal-title":"Arq Bras Cardiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1161\/HYPERTENSIONAHA.110.156141","article-title":"Exercise training and caloric restriction prevent reduction in cardiac Ca2+-handling protein profile in obese rats","volume":"56","author":"E C Paulino","year":"2010","journal-title":"Hypertension"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1152\/japplphysiol.91218.2008","article-title":"Exercise capacity is related to calcium transients in ventricular cardiomyocytes","volume":"107","author":"T N Pr\u00edmola-Gomes","year":"2009","journal-title":"J Appl Physiol (1985)"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2165\/00129784-200606020-00002","article-title":"Mechanisms, manifestations, and management of digoxin toxicity in the modern era.","volume":"6","author":"J L Bauman","year":"2006","journal-title":"Am J Cardiovasc Drugs"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1046\/j.1439-0442.2002.00414.x","article-title":"Digoxin- and monensin-induced changes of intracellular ca2+ concentration in isolated guinea-pig ventricular myocyte","volume":"49","author":"I Meral","year":"2002","journal-title":"J Vet Med A Physiol Pathol Clin Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1055\/s-0042-119727","article-title":"Digoxin induces cardiac hypertrophy without negative effects on cardiac function and physical performance in trained normotensive rats","volume":"38","author":"C H Neves","year":"2017","journal-title":"Int J Sports Med"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1055\/a-1015-3123","article-title":"Ethical standards in sport and exercise science research: 2020 update","volume":"40","author":"D J Harriss","year":"2019","journal-title":"Int J Sports Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1291\/hypres.23.Supplement_S77","article-title":"Chronic hypertension induced by oubain but not digoxin in the heart: Antihypertensive effect of digoxin and digitoxin","volume":"23","author":"P Manunta","year":"2000","journal-title":"Hypertens Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/0002-9149(85)90778-7","article-title":"Acute effects of digoxin on total systemic vascular resistance in congestive heart failure due to dilated cardiomyopathy: A hemodynamic hormonal study","volume":"56","author":"H S Ribner","year":"1985","journal-title":"Am J Cardiol"},{"key":"ref14","first-page":"96","article-title":"Running training effects in different intensities on the aerobic capacity and lactate production by the muscle of Wistar rats","volume":"13","author":"F B Manchado","year":"2007","journal-title":"Motriz"},{"key":"ref15","first-page":"398","article-title":"Digoxin and verapamil promote cardiomyocyte hypertrophy in sedentary and\/or trained rats","volume":"22","author":"C H Neves","year":"2016","journal-title":"Rev Bras Med Esporte"},{"key":"ref16","first-page":"H941","article-title":"Use of tibial length to quantify cardiac hypertrophy: application in the aging rat","volume":"24","author":"F C Yin","year":"1982","journal-title":"Am J Physiol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.yjmcc.2011.06.012","article-title":"Methods in cardiomyocyte isolation, culture, and gene transfer","volume":"51","author":"W E Louch","year":"2011","journal-title":"J Mol Cell Cardiol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"633","DOI":"10.33549\/physiolres.931928","article-title":"Animal models in the study of exercise-induced cardiac hypertrophy","volume":"59","author":"Y Wang","year":"2010","journal-title":"Physiol Res"},{"key":"ref19","first-page":"2194120","article-title":"Effect of high intensity interval and continuous swimming training on body mass adiposity level and serum parameters in high-fat diet fed rats","volume":"2016","author":"GL D Rocha","year":"2016","journal-title":"ScientificWorldJournal"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/oby.21056","article-title":"Effect of different exercise protocols on metabolic profiles and fatty acid metabolism in skeletal muscle in high-fat diet-fed rats","volume":"23","author":"Y Shen","year":"2015","journal-title":"Obesity"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2337\/diacare.20.3.385","article-title":"Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM: Effects of branched-chain amino acid supplements","volume":"20","author":"A Mourier","year":"1997","journal-title":"Diabetes Care"},{"key":"ref22","first-page":"72","article-title":"Weigth loss strategies","volume":"6","author":"C Hauser","year":"2006","journal-title":"Rev Bras Cineantropom Desempenho Hum"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1258\/smj.2011.011284","article-title":"Walk or run? Is high-intensity exercise more effective than moderate intensity exercise at reducing cardiovascular risk?","volume":"57","author":"A J Rankin","year":"2012","journal-title":"Scott Med J"},{"key":"ref24","first-page":"702","article-title":"Is moderate intensity exercise training combined with high intensity interval training more effective at improving cardio respiratory fitness than moderate intensity exercise training alone?","volume":"13","author":"B H Roxburgh","year":"2014","journal-title":"J Sports Sci Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1249\/01.mss.0000233799.62153.19","article-title":"Training for endurance and strength: Lessons from cell signaling","volume":"38","author":"K Baar","year":"2006","journal-title":"Med Sci Sports Exerc"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1139\/H08-097","article-title":"High-intensity aerobic interval training increases fat and carbohydrate metabolic capacities in human skeletal muscle","volume":"33","author":"CG R Perry","year":"2008","journal-title":"Appl Physiol Nutr Metab"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1113\/JP273196","article-title":"Physiological adaptations to interval training and the role of exercise intensity","volume":"595","author":"M J MacInnis","year":"2017","journal-title":"J Physiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/17461391.2019.1615556","article-title":"Mitochondrial adaptations to high intensity interval training in older females and males","volume":"20","author":"K M Chr\u00f8is","year":"2020","journal-title":"Eur J Sport Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1378\/chest.82.5.543","article-title":"The effect of digoxin on exercise capacity and exercising cardiac function in cystic fibrosis","volume":"82","author":"A L Coates","year":"1982","journal-title":"Chest"},{"key":"ref30","first-page":"960","article-title":"Effects of digoxin on the oxygen debt and the exercise electrocardiogram in normal subjects","volume":"97","author":"W J Friesen","year":"1967","journal-title":"Can Med Assoc J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"98","DOI":"10.5694\/j.1326-5377.2003.tb05445.x","article-title":"Digoxin in heart failure and cardiac arrhythmias","volume":"179","author":"T J Campbell","year":"2003","journal-title":"Med J Aust"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/0735-1097(89)90276-3","article-title":"Increased exercise capacity after digoxin administration in patients with heart failure","volume":"13","author":"M Sullivan","year":"1989","journal-title":"J Am Coll Cardiol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1056\/NEJM198903163201101","article-title":"A comparison of oral milrinone, digoxin and their combination in the treatment of patients with chronic heart failure","volume":"320","author":"R Di Bianco","year":"1989","journal-title":"N Engl J Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0735-1097(10)80194-9","article-title":"Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial","volume":"17","author":"J L Fleg","year":"1991","journal-title":"J Am Coll Cardiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0002-9149(97)89341-1","article-title":"Influence of digitalis on left ventricular functional response to exercise in congestive heart failure","volume":"77","author":"C Morisco","year":"1996","journal-title":"Am J Cardiol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1097\/00005768-200004000-00011","article-title":"Intra-and extra-cellular lactate shuttles","volume":"32","author":"G A Brooks","year":"2000","journal-title":"Med Sci Sports Exerc"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"H543","DOI":"10.1152\/ajpheart.00899.2014","article-title":"Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs","volume":"309","author":"T Fernandes","year":"2015","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1136\/heartjnl-2011-300639","article-title":"Physiological cardiac remodelling in response to endurance exercise training: Cellular and molecular mechanisms","volume":"98","author":"G M Ellison","year":"2012","journal-title":"Heart"},{"key":"ref39","first-page":"62","article-title":"Cardiac remodeling: Concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment","volume":"106","author":"P S Azevedo","year":"2016","journal-title":"Arq Bras Cardiol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4103\/jrms.JRMS_292_18","article-title":"Regulation of PI3K and Hand2 gene on physiological hypertrophy of heart following high-intensity interval, and endurance training","volume":"24","author":"M A Gharaat","year":"2019","journal-title":"J Res Med Sci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1038\/s41598-019-42023-1","article-title":"High intensity training improves cardiac function in healthy rats","volume":"9","author":"M Verboven","year":"2019","journal-title":"Sci Rep"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00421-010-1578-4","article-title":"The effects of aerobic interval training on the left ventricular morphology and function of VLCAD-deficient mice","volume":"110","author":"C E Riggs","year":"2010","journal-title":"Eur J Appl Physiol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.lfs.2015.01.007","article-title":"Evidence for distinct effects of exercise in different cardiac hypertrophic disorders","volume":"123","author":"E J Johnson","year":"2015","journal-title":"Life Sci"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pharmthera.2010.04.005","article-title":"Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies","volume":"128","author":"B C Bernardo","year":"2010","journal-title":"Pharmacol Ther"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/iub.545","article-title":"Calcium-regulated transcriptional pathways in the normal and pathologic heart","volume":"63","author":"A Zarain-Herzberg","year":"2011","journal-title":"IUBMB Life"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yjmcc.2016.06.001","article-title":"Physiological and pathological cardiac hypertrophy","volume":"97","author":"I Shimizu","year":"2016","journal-title":"J Mol Cell Cardiol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1113\/jphysiol.2009.173948","article-title":"Cardiac anti-remodelling effect of aerobic training is associated with a reduction in the calcineurin\/NFAT signalling pathway in heart failure mice","volume":"587","author":"RS F Oliveira","year":"2009","journal-title":"J Physiol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"e66288","DOI":"10.1371\/journal.pone.0066288","article-title":"Aerobic interval training partly reverse contractile dysfunction and impaired Ca2+ handling in atrial myocytes from rats with post infarction heart failure","volume":"8","author":"A B Johnsen","year":"2013","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ahj.2018.02.004","article-title":"Prevalent digoxin use and subsequent risk of death or hospitalization in ambulatory heart failure patients with a reduced ejection fraction-Findings from the heart failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized controlled trial","volume":"199","author":"A P Ambrosy","year":"2018","journal-title":"Am Heart J"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.tcm.2016.03.011","article-title":"Digoxin: The good and the bad","volume":"26","author":"O J Ziff","year":"2016","journal-title":"Trends Cardiovasc Med"},{"key":"ref51","first-page":"729","volume-title":"Digitalis and allied cardiac glycosides","author":"B F Hoffman","year":"1980"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/JES.0b013e3181aa65fc","article-title":"High-intensity interval training to maximize cardiac benefits of exercise training?","volume":"37","author":"U Wisloff","year":"2009","journal-title":"Exerc Sport Sci Rev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1249\/MSS.0000000000001931","article-title":"High intensity interval training improves left ventricular contractile function","volume":"51","author":"Y C Huang","year":"2019","journal-title":"Med Sci Sports Exerc"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1748-1716.2010.02132.x","article-title":"Mechanisms of exercise induced improvements in the contractile apparatus of the mammalian myocardium","volume":"199","author":"O J Kemi","year":"2010","journal-title":"Acta Physiol (Oxf)"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1249\/00003677-199900270-00011","article-title":"Exercise training and cellular adaptations of normal and diseased hearts","volume":"27","author":"R L Moore","year":"1999","journal-title":"Exerc Sport Sci Rev"},{"key":"ref56","first-page":"426","article-title":"Functions of selected biochemical systems from the exercised-trained dog heart","volume":"42","author":"L A Sordahl","year":"1977","journal-title":"J Appl Physiol Respir Environ Exerc Physiol"},{"key":"ref57","first-page":"172","article-title":"Physical exercise and regulation of intracellular calcium in cardiomyocytes of hypertensive rats","volume":"111","author":"J A Rodrigues","year":"2018","journal-title":"Arq Bras Cardiol"}],"container-title":["International Journal of Sports Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1300-2583.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T22:46:13Z","timestamp":1625697973000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1300-2583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":57,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2021,7,7]]},"published-print":{"date-parts":[[2021,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1300-2583","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0172-4622","1439-3964"],"issn-type":[{"type":"print","value":"0172-4622"},{"type":"electronic","value":"1439-3964"}],"subject":[],"published":{"date-parts":[[2020,12,15]]}}}