Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly

Autoři: Nayeli Iwanuk aff001;  Leona Wall aff001;  Ingo Nolte aff001;  Jonathan Raue aff001;  Katja Rumstedt aff001;  Anna Pilgram aff001;  Maximiliane Sehn aff001;  Karl Rohn aff002;  Jan-Peter Bach aff001
Působiště autorů: Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany aff001;  Institute of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223164


Pimobendan has gained enormous importance in the treatment of mitral valve disease in dogs. The current consensus statement of the American College of Veterinary Internal Medicine (ACVIM) recommends a treatment for dogs with symptomatic disease and dogs with asymptomatic disease with radiographic and echocardiographic signs of cardiomegaly. To investigate whether these dogs also benefit from a therapy with pimobendan, 21 dogs with mitral valve disease ACVIM B1 underwent a standardized submaximal exercise test on a treadmill. In this double-blinded and randomized study, the animals were divided into two groups, one receiving pimobendan and the other a placebo. At the first visit and at every follow-up appointment (at days 90 and 180), heart rate during the complete exercise test and lactate before and after running were measured. In addition to this, a questionnaire was completed by the dogs’ owners and all dogs were given an echocardiographic examination to detect any changes and to observe if the disease had progressed. Due to the diagnosis of leishmaniosis, one dog in the pimobendan group was retrospectively removed from the study so that 20 dogs were included for statistical analysis. No differences were observed at any time between the pimobendan-group and the placebo-group regarding heart rate. At day 180, the increase in lactate after exercise was significantly lower than in the placebo-group. The increase in the pimobendan-group at day 180 was lower than at day 90. Most of the dog owners from the pimobendan-group declared that their dogs were more active at day 90 (6/10) and at day 180 (8/10), while most dog owners from the placebo-group observed no changes regarding activity at day 90 (8/10) and day 180 (6/10). It can be concluded that the results of this study indicate that some dogs with mitral valve disease ACVIM B1 might benefit from a therapy with pimobendan.

Klíčová slova:

Dogs – Exercise – Heart rate – Pets and companion animals – Physical fitness – Quality of life – Sports and exercise medicine – Veterinary diseases


1. Atkins C, Bonagura J, Ettinger S, Fox P, Gordon S, Haggstrom J, et al. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. Journal of veterinary internal medicine. 2009;23(6):1142–50. doi: 10.1111/j.1939-1676.2009.0392.x 19780929

2. Detweiler D, Patterson D. The prevalence and types of cardiovascular disease in dogs. Annals of the New York Academy of Sciences. 1965;127(1):481–516. doi: 10.1111/j.1749-6632.1965.tb49421.x 5217276

3. Keene BW, Atkins CE, Bonagura JD, Fox PR, Häggström J, Fuentes VL, et al. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. Journal of veterinary internal medicine. 2019.

4. Schneider P, Güttner J, Eckenfels A, Heinzel G, Nicolai Hv, Trieb G, et al. Comparative cardiac toxicity of the IV administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs. Experimental and Toxicologic Pathology. 1997;49(3–4):217–24. 9314056

5. Tissier R, Chetboul V, Moraillon R, Nicolle A, Carlos C, Enriquez B, et al. Increased mitral valve regurgitation and myocardial hypertrophy in two dogs with long-term pimobendan therapy. Cardiovascular toxicology. 2005;5(1):43–51. 15738584

6. Chetboul V, Lefebvre HP, Sampedrano CC, Gouni V, Saponaro V, Serres F, et al. Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study. Journal of veterinary internal medicine. 2007;21(4):742–53. doi: 10.1892/0891-6640(2007)21[742:caceop]2.0.co;2 17708394

7. Boswood A, Haggstrom J, Gordon SG, Wess G, Stepien RL, Oyama MA, et al. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med. 2016;30(6):1765–79. doi: 10.1111/jvim.14586 27678080

8. Oyama MA, Rush JE, O'Sullivan ML, Williams RM, Rozanski EA, Petrie J-P, et al. Perceptions and priorities of owners of dogs with heart disease regarding quality versus quantity of life for their pets. Journal of the American Veterinary Medical Association. 2008;233(1):104–8. doi: 10.2460/javma.233.1.104 18593317

9. Freeman LM, Rush JE, Farabaugh AE, Must A. Development and evaluation of a questionnaire for assessing health-related quality of life in dogs with cardiac disease. Journal of the American Veterinary Medical Association. 2005;226(11):1864–8. doi: 10.2460/javma.2005.226.1864 15934254

10. Wiseman-Orr ML, Scott EM, Reid J, Nolan AM. Validation of a structured questionnaire as an instrument to measure chronic pain in dogs on the basis of effects on health-related quality of life. American journal of veterinary research. 2006;67(11):1826–36. doi: 10.2460/ajvr.67.11.1826 17078742

11. Tipton C, Carey R, Eastin W, Erickson H. A submaximal test for dogs: evaluation of effects of training, detraining, and cage confinement. Journal of Applied Physiology. 1974;37(2):271–5. doi: 10.1152/jappl.1974.37.2.271 4850334

12. Boddy KN, Roche BM, Schwartz DS, Nakayama T, Hamlin RL. Evaluation of the six-minute walk test in dogs. American journal of veterinary research. 2004;65(3):311–3. doi: 10.2460/ajvr.2004.65.311 15027678

13. Ferasin L, Marcora S. Reliability of an incremental exercise test to evaluate acute blood lactate, heart rate and body temperature responses in Labrador retrievers. J Comp Physiol B. 2009;179(7):839–45. doi: 10.1007/s00360-009-0367-z 19455341

14. Piccione G, Casella S, Panzera M, Giannetto C, Fazio F. Effect of moderate treadmill exercise on some physiological parameters in untrained beagle dogs. Experimental animals. 2012;61(5):511–5. doi: 10.1538/expanim.61.511 23095814

15. Wall L, Mohr A, Ripoli FL, Schulze N, Penter CD, Hungerbuehler S, et al. Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation. PloS one. 2018;13(6):e0199023. doi: 10.1371/journal.pone.0199023 29902265

16. Kittleson MD, Johnson LE, Pion PD. Submaximal exercise testing using lactate threshold and venous oxygen tension as endpoints in normal dogs and in dogs with heart failure. Journal of veterinary internal medicine. 1996;10(1):21–7. doi: 10.1111/j.1939-1676.1996.tb02019.x 8965264

17. Spriet L. Anaerobic metabolism during exercise. Exercise metabolism. 2006;2:7–28.

18. Cerretelli P, Piiper J, Mangili F, Ricci B. Aerobic and anaerobic metabolism in exercising dogs. Journal of applied physiology. 1964;19(1):25–8.

19. Kubo SH, Gollub S, Bourge R, Rahko P, Cobb F, Jessup M, et al. Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group. Circulation. 1992;85(3):942–9. doi: 10.1161/01.cir.85.3.942 1537130

20. Lubsen J, Just H, Hjalmarsson A, La Framboise D, Remme W, Heinrich-Nols J, et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart. 1996;76(3):223–31. doi: 10.1136/hrt.76.3.223 8868980

21. Hansson K, Häggström J, Kvart C, Lord P. Left atrial to aortic root indices using two‐dimensional and M‐mode echocardiography in cavalier King Charles spaniels with and without left atrial enlargement. Veterinary Radiology & Ultrasound. 2002;43(6):568–75.

22. Cornell CC, Kittleson MD, Torre PD, Häggström J, Lombard CW, Pedersen HD, et al. Allometric scaling of M‐mode cardiac measurements in normal adult dogs. Journal of veterinary internal medicine. 2004;18(3):311–21. doi: 10.1892/0891-6640(2004)18<311:asomcm>2.0.co;2 15188817

23. Buchanan JW, Bücheler J. Vertebral scale system to measure canine heart size in radiographs. JOURNAL-AMERICAN VETERINARY MEDICAL ASSOCIATION. 1995;206:194–.

24. Iwanuk N, Nolte I, Wall L, Sehn M, Raue J, Pilgram A, et al. Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly—a randomised, double-blinded trial. BMC Vet Res. 2019;15(1):237. doi: 10.1186/s12917-019-1980-z 31288807

25. Sneddon J, Minnaar P, Grosskopf J, Groeneveld H. Physiological and blood biochemical responses to submaximal treadmill exercise in Canaan dogs before, during and after training. Journal of the South African Veterinary Association. 1989;60(2):87–91. 2607537

26. Ferasin L, Marcora S. A pilot study to assess the feasibility of a submaximal exercise test to measure individual response to cardiac medication in dogs with acquired heart failure. Vet Res Commun. 2007;31(6):725–37. doi: 10.1007/s11259-007-3566-7 17253114

27. Spengler CM, Roos M, Laube SM, Boutellier U. Decreased exercise blood lactate concentrations after respiratory endurance training in humans. European journal of applied physiology and occupational physiology. 1999;79(4):299–305. doi: 10.1007/s004210050511 10090627

28. Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. American Review of Respiratory Disease. 1991;143(1):9–18. doi: 10.1164/ajrccm/143.1.9 1986689

29. Boswood A, Gordon SG, Häggström J, Wess G, Stepien RL, Oyama MA, et al. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with preclinical myxomatous mitral valve disease receiving pimobendan or placebo: the EPIC study. J Vet Intern Med. 2018;32(1):72–85. doi: 10.1111/jvim.14885 29214723

30. Swimmer RA, Rozanski EA. Evaluation of the 6‐minute walk test in pet dogs. Journal of veterinary internal medicine. 2011;25(2):405–6. doi: 10.1111/j.1939-1676.2011.0689.x 21352372

Článek vyšel v časopise


2019 Číslo 10
Nejčtenější tento týden