Effect of Single-dose Pimobendan on Echocardiographic Parameters in Healthy New Zealand White Rabbits

Document Type : Research Article

Authors

1 Department of Veterinary Clinical Sciences, Karaj branch, Islamic Azad University, Karaj, Iran.

2 Department of Pharmacology, Karaj branch, Islamic Azad University, Karaj, Iran.

3 Department of Radiology, Karaj branch, Islamic Azad University, Karaj, Iran.

4 Department of Surgery and Radiology, Faculty of veterinary medicine, University of Tehran, Tehran, Iran.

Abstract

keeping rabbits as pets and their use in laboratory research increased the need for studying heart diseases and treatments in rabbits. Pimobendan is one of the most common medications used in cardiac diseases and is anecdotal in rabbits. The first step toward the approval of pimobendan in rabbits is assessing the potential for beneficial effects on cardiac function through echocardiographic functional parameters.This study aimed to determine the effects of pimobendan on echocardiographic parameters. Eleven rabbits were included in this study. Echocardiographic examinations were performed before and after pimobendan administration for each rabbit. The LV morphological and functional parameters were compared between study time points. Pimobendan resulted in changes in several echocardiographic variables in the rabbits, including FS and an increase in EF, SV, LVPWs, and LA end-systolic (p = 0.0001, p = 0.0001, p = 0.0284, p = 0.0272, and p = 0.0007, respectively). Moreover, LVIDs and end-systolic volume decreased (p = 0.0343 and p = 0.038). The changes in some parameters were not significant, such as LVIDd, LVPWd, end-diastolic volume, LA max,  Mitral annulus diameter, and LA/Ao. FS, which indicates an increase in the power of heart contraction and consequently an improvement in heart function, increased in this study after pimobendan administration. Therefore, it can be concluded that pimobendan improves cardiac functions. Further studies are required to investigate whether pimobendan has similar effects in rabbits with cardiac diseases. 

Keywords

Main Subjects


1.    Yata M, McLachlan AJ, Foster DJR, Hanzlicek AS, Beijerink NJ. Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats. Journal of Veterinary Cardiology. 2016 Dec 1;18(4):310–25. Doi: 10.1016/j.jvc.2016.07.001.
2.    Yata M, McLachlan AJ, Foster DJR, Page SW, Beijerink NJ. Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs. J Vet Pharmacol Ther. 2016;39(1):45–53. Doi: 10.111/JVP.12243.
3.    Yanni AE. The laboratory rabbit: An animal model of atherosclerosis research. Lab Anim [Internet]. 2004 Jul 23 [cited 2022 Aug 4];38(3):246–56. Doi: 10.1258/002367704323133628.
4.    Gava FN, Zacché E, Ortiz EMG, Champion T, Bandarra MB, Vasconcelos RO, et al. Doxorubicin induced dilated cardiomyopathy in a rabbit model: An update. Res Vet Sci. 2013;94(1):115–21. Doi: 10.1016/j.rvsc.2012.07.027.
5.    Lord B, Boswood A, Petrie A. Electrocardiography of the normal domestic pet rabbit. Veterinary Record [Internet]. 2010 Dec 1 [cited 2022 Aug 4];167(25):961–5. Doi: 10.1136/vr.c3212.
6.    Turner Giannico A, Ayres Garcia DA, Lima L, de Lara FA, Corona Ponczek CA, Shaw GC, et al. Determination of Normal Echocardiographic, Electrocardiographic, and Radiographic Cardiac Parameters in the Conscious New Zealand White Rabbit. J Exot Pet Med. 2015;24(2):223–34. Doi: 10.1053/j.jepm.2015.04.013.
7.    Harvey L, Knowles T, Murison PJ. Comparison of direct and Doppler arterial blood pressure measurements in rabbits during isoflurane anaesthesia. Vet Anaesth Analg. 2012;39(2):174–84. Doi: 10.1111/j.1467-2995.2011.00685x.
8.    Sato K, Chatani F, Sato S. Circadian and short-term variabilities in blood pressure and heart rate measured by telemetry in rabbits and rats. J Auton Nerv Syst. 1995;54(3):235–46. Doi: 10.1016/0165-1838(95)00016-Q.
9.    Hagemeijer F. Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. Eur Heart J [Internet]. 1993[cited 2022];14(4):551–66. Doi: 10.1093/eurheartj/14.4.551.
10.    Ozawa SM, Guzman DSM, Hawkins MG, Diao SM, Masri AE, Gunther-Harrington CT, et al. Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus). Am J Vet Res [Internet]. 2022 [cited 2022];83(4):356–63. Doi: 10.2460/ajvr21.03.0032.
11.    Ouellet M, Bélanger MC, DiFruscia R, Beauchamp G. Effect of pimobendan on echocardiographic values in dogs with asymptomatic mitral valve disease. J Vet Intern Med. 2009;23(2). Doi: 10.111/j.1939-1676-2008.0239.x.
12.    Saengklub N, Boonyarattanasoonthorn T, Kijtawornrat A, Chantasart D. Preliminary Bioequivalence of an Oral Pimobendan Solution Formulation with Reference Solution Formulation in Beagle Dogs. Vet Sci. 2022;9(3). Doi: 10.3390/vetsci9030141.
13.    Klein S, Nolte I, Rumstedt K, Sehn M, Raue JF, Weiner F, et al. The effect of treatment with pimobendan in dogs with preclinical mitral valve disease – a placebo-controlled double-blinded crossover study. BMC Vet Res. 2021;17(1).  Doi: 10.1186/s12917-021-03014-5.
14.    Häggström J, Boswood A, O’Grady M, Jöns O, Smith S, Swift S, et al. 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. J Vet Intern Med. 2013;27(6). Doi: 10.1111/jvim.12181.
15.    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). Doi: 10.1111/jvim.14885.
16.    Serres F, Chetboul V, Tissier R, Poujol L, Gouni V, Carlos Sampedrano C, et al. Comparison of 3 ultrasound methods for quantifying left ventricular systolic function: Correlation with disease severity and prognostic value in dogs with mitral valve disease. J Vet Intern Med. 2008;22(3). Doi: 10.1111/J.1939-1676.2008.0097.x.
17.    Tissot C, Singh Y, Sekarski N. Echocardiographic evaluation of ventricular function-for the neonatologist and pediatric intensivist. Vol. 6, Frontiers in Pediatrics. 2018. Doi: 10.3389/fped.2018.00079.
18.    Ro W Bin, Song DW, Kim KH, Jeong SH, Kang MH. Pharmacokinetics and pharmacodynamics of pimobendan-pentoxifylline liquid mixture after oral administration in dogs. Journal of Veterinary Clinics. 2019;36(3). Doi:10.17555/jvc.2019.06.36.3.159.
19.    Uehara Y, Takahashi M, Koga M. Determination of cardiac output by echocardiography. Journal of Veterinary Medical Science. 1995;57(3). Doi: 10.1292/jvms.57.401.
20.    Sergeev D, Kovalev S, Trushkin V, Vasilev R, Nikitina A, Kiselenko P, et al. Use of high doses of pimobendan in animals with dilated cardiomyopathy. The FASEB Journal. 2021;35(S1). Doi: 10.1096/FASEBJ.2021.35.S1.01489.
21.    Kanno N, Kuse H, Kawasaki M, Hara A, Kano R, Sasaki Y. Effects of pimobendan for mitral valve regurgitation in dogs. Journal of Veterinary Medical Science. 2007;69(4). Doi: 10.1292/JVMS.69.373.
22.    Abbott-Johnson K, Pierce KV, Roof S, Del Rio CL, Hamlin R. Acute Effects of Pimobendan on Cardiac Function in Dogs With Tachycardia Induced Dilated Cardiomyopathy: A Randomized, Placebo-Controlled, Crossover Study. Front Vet Sci. 2021;8:646437. doi: 10.3389/fvets.2021.646437.
23.    Sarcinella F, Neves J, Maddox TW, Hodgkiss-Geere HM, Bode EF, Dukes-Mcewan J. Effect of pimobendan on left atrial function in dogs with preclinical myxomatous mitral valve disease. Open Vet J. 2019;9(4):375–83. Doi: 10.4314/ovj.v9i4.16.
24.    Kochie SL, Schober KE, Rhinehart J, Winter RL, Bonagura JD, Showers A, et al. Effects of pimobendan on left atrial transport function in cats. J Vet Intern Med. 2021;35(1). Doi: 10.111/jvim.15976.
25. Boon, J.A. In: Boon, J.A., editor. Two-dimensional and M-mode Echocardiography for Small Animal Practitioner. 2nd ed. John Wiley and Sons Inc., New York, United states. 2016. Doi: 10.1002/9781119028574
26.    Kost LV, Glaus TM, Diana A, Baron Toaldo M. Effect of a single dose of pimobendan on right ventricular and right atrial function in 11 healthy cats. J Vet Cardiol. 2021;37:52-61. Doi: 10.1016/j.jvc.2021.08.006. 
CAPTCHA Image