{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:10:32Z","timestamp":1783091432199,"version":"3.54.6"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Pimobendan provides a significant survival benefit in dogs with cardiac disease, including degenerative mitral valve disease and dilated cardiomyopathy (DCM). Its positive inotropic effect is well-known, however, it has complex effects and the mechanisms behind the survival benefit are not fully characterized. Secondary hemodynamic effects may decrease mitral regurgitation (MR) in DCM, and the benefits of pimobendan may extend to improved cardiac relaxation and improved atrial function.<\/jats:p><jats:p><jats:bold>Hypothesis\/Objectives:<\/jats:bold> Our objective was to investigate the acute cardiac effects of pimobendan in dogs with a DCM phenotype. We hypothesized that pimobendan would increase left atrial (LA) contractility, reduce mitral regurgitation, improve diastolic function, and lower circulating NT-ProBNP levels.<\/jats:p><jats:p><jats:bold>Animals:<\/jats:bold> Seven purpose-bred Beagles were studied from a research colony with tachycardia induced DCM phenotype.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The effects of pimobendan were studied under a placebo-controlled single-blinded cross-over design. In short, dogs underwent baseline and 3 h post-dose examinations 7 days apart with echocardiography and a blood draw. Dogs were randomized to receive oral placebo or 0.25 mg\/kg pimobendan after their baseline exam. Investigators were blinded to treatments until all measurements were compiled.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> When treated with pimobendan, the dogs had significant increases in systolic function and decreases in MR, compared to when treated with placebo.<\/jats:p><jats:p>There were no detectable differences in left atrial measures, including LA size, LA emptying fraction, LA functional index or mitral A wave velocity. Heart rate decreased significantly with pimobendan compared to placebo. There was also a decrease in isovolumetric relaxation time normalized to heart rate. NT-proBNP levels had a high degree of variability.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Improved mitral regurgitation severity and improved lusitropic function may contribute to the reported survival benefit for dogs with cardiac disease administered pimobendan. Pimobendan did not overtly improve LA function as assessed by echocardiography, and NT-proBNP was not significantly changed with a single dose of this medication. Further studies are needed to better characterize LA effects with other imaging modalities, to better quantify the total improvement of MR severity, and to assess chronic use of pimobendan on diastolic function in DCM.<\/jats:p>","DOI":"10.3389\/fvets.2021.646437","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T14:08:00Z","timestamp":1625148480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Acute Effects of Pimobendan on Cardiac Function in Dogs With Tachycardia Induced Dilated Cardiomyopathy: A Randomized, Placebo-Controlled, Crossover Study"],"prefix":"10.3389","volume":"8","author":[{"given":"Kaitlin","family":"Abbott-Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kursten V.","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Roof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos L. del","family":"Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hamlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1111\/j.1939-1676.2012.01026.x","article-title":"Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study)","volume":"26","author":"Summerfield","year":"2012","journal-title":"J Vet Int Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1111\/jvim.14586","article-title":"Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the EPIC study-a randomized clinical trial","volume":"30","author":"Boswood","year":"2016","journal-title":"J Vet Int Med"},{"key":"B3","first-page":"103","article-title":"New positive inotropic substances\u2013true inotropy or peripheral effects?","author":"Wilmshurst","year":"1988","journal-title":"Z Kardiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.2165\/00002512-199404050-00007","article-title":"Pimobendan. A review of its pharmacology and therapeutic potential in congestive heart failure","volume":"4","author":"Fitton","year":"1994","journal-title":"Drugs Aging."},{"key":"B5","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/j.1939-1676.2002.tb02366.x","article-title":"A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy","volume":"16","author":"Fuentes","year":"2002","journal-title":"J Vet Intern Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1111\/jvim.12181","article-title":"Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study","volume":"27","author":"H\u00e4ggstr\u00f6m","year":"2013","journal-title":"J Vet Intern Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jvc.2020.02.002","article-title":"Effect of pimobendan on left atrial function: an echocardiographic pilot study in 11 healthy cats","volume":"28","author":"Baron Toaldo","year":"2020","journal-title":"J Vet Cardiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3389\/fvets.2019.00015","article-title":"Cardiac effects of a single dose of pimobendan in cats with hypertrophic cardiomyopathy; a randomized, placebo-controlled, crossover study","volume":"6","author":"Oldach","year":"2019","journal-title":"Front Vet Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"375","DOI":"10.4314\/ovj.v9i4.16","article-title":"Effect of pimobendan on left atrial function in dogs with preclinical myxomatous mitral valve disease","volume":"9","author":"Sarcinella","year":"2020","journal-title":"Open Vet J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1385\/CT:5:1:043","article-title":"Increased mitral valve regurgitation and myocardial hypertrophy in two dogs with long-term pimobendan therapy","volume":"5","author":"Tissier","year":"2005","journal-title":"Cardiovasc Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1292\/jvms.69.373","article-title":"Effects of pimobendan for mitral valve regurgitation in dogs","volume":"69","author":"Kanno","year":"2007","journal-title":"J Vet Med Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/j.1939-1676.2008.0239.x","article-title":"Effect of pimobendan on echocardiographic values in dogs with asymptomatic mitral valve disease","volume":"23","author":"Ouellet","year":"2009","journal-title":"J Vet Intern Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1161\/01.CIR.60.1.170","article-title":"Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area","volume":"60","author":"Yoran","year":"1979","journal-title":"Circulation"},{"key":"B14","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/00005344-199402000-00014","article-title":"Disparate inotropic and lusitropic responses to pimobendan in conscious dogs with tachycardia-induced heart failure","volume":"23","author":"Asanoi","year":"1994","journal-title":"J Cardiovasc Pharmacol."},{"key":"B15","first-page":"23","article-title":"The cardiac effects of pimobendan (but not amrinone) are preserved at rest and during exercise in conscious dogs with pacing-induced heart failure","volume":"282","author":"Ohte","year":"1997","journal-title":"J Pharmacol Exp Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/jvp.12243","article-title":"Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs","volume":"39","author":"Yata","year":"2016","journal-title":"J Vet Pharmacol Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/jvp.12235","article-title":"The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs","volume":"39","author":"Bell","year":"2016","journal-title":"J Vet Pharmacol Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jvc.2018.08.002","article-title":"Transvenous pacing implantation: techniques, tips, and lessons learned along the way","volume":"22","author":"Estrada","year":"2019","journal-title":"J Vet Cardiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.jacbts.2018.07.003","article-title":"Intravenous infusion of the novel HNO donor BMS-986231 is associated with beneficial inotropic, lusitropic, and vasodilatory properties in 2 canine models of heart failure","volume":"3","author":"Hartman","year":"2018","journal-title":"JACC Basic Transl Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1254\/jphs.13196FP","article-title":"Comparative evaluation of calcium-sensitizing agents, pimobendan and SCH00013, on the myocardial function of canine pacing-induced model of heart failure","volume":"124","author":"Hamabe","year":"2014","journal-title":"J Pharmacol Sci"},{"key":"B21","article-title":"Veterinary Echocardiography","author":"Boon","year":"2011"},{"key":"B22","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1590\/S0100-736X2016000800011","article-title":"Determination of left atrial volume in healthy dogs and dogs with myxomatous mitral valve disease","volume":"36","author":"Franco","year":"2016","journal-title":"Pesq Vet Bras."},{"key":"B23","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.euje.2007.06.002","article-title":"The left atrial function index: a rhythm independent marker of atrial function","volume":"9","author":"Thomas","year":"2008","journal-title":"Eur J Echocardiogr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1111\/jvim.15461","article-title":"Echocardiographic indices and severity of mitral regurgitation in dogs with preclinical degenerative mitral valve disease","volume":"33","author":"Larouche-Lebel","year":"2019","journal-title":"J Vet Intern Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S1760-2734(06)70050-9","article-title":"Regurgitant jet area by Doppler color flow mapping: quantitative assessment of mitral regurgitation severity in dogs","volume":"5","author":"Muzzi","year":"2003","journal-title":"J Vet Cardiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/j.1939-1676.2004.tb02604.x","article-title":"Echocardiographic estimation of mean left atrial pressure in a canine model of acute mitral valve insufficiency","volume":"18","author":"Oyama","year":"2004","journal-title":"J Vet Intern Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/aas.13170","article-title":"Inotropic and lusitropic effects of levosimendan and milrinone assessed by strain echocardiography-A randomised trial","volume":"62","author":"Fredholm","year":"2018","journal-title":"Acta Anaesthesiol Scand."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/ejhf.1933","article-title":"Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial","volume":"22","author":"Voors","year":"2020","journal-title":"Eur J Heart Fail."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1111\/j.1939-1676.2011.00800.x","article-title":"The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation","volume":"25","author":"Suzuki","year":"2011","journal-title":"J Vet Intern Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1111\/jvim.12217","article-title":"Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure","volume":"27","author":"H\u00e4ggstr\u00f6m","year":"2013","journal-title":"J Vet Intern Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"642","DOI":"10.2460\/ajvr.72.5.642","article-title":"Evaluation of N-terminal pro-B-type natriuretic peptide as a diagnostic marker of various stages of cardiomyopathy in Doberman Pinschers","volume":"72","author":"Wess","year":"2011","journal-title":"Am J Vet Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/jvim.12310","article-title":"Breed Differences in Natriuretic Peptides in Healthy Dogs","volume":"28","author":"Sj\u00f6strand","year":"2014","journal-title":"J Vet Int Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.vascn.2018.06.001","article-title":"Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines","volume":"93","author":"Gao","year":"2018","journal-title":"J Pharmacol Toxicol Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/978-1-4939-8597-5_24","article-title":"Canine model of pacing-induced heart failure","volume":"1816","author":"Powers","year":"2018","journal-title":"Methods Mol Biol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.646437\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T14:08:05Z","timestamp":1625148485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2021.646437\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":34,"alternative-id":["10.3389\/fvets.2021.646437"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2021.646437","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]},"article-number":"646437"}}