Effect of standard‐dose and high‐dose pimobendan on select indices of renal and cardiac function in dogs with American College of Veterinary Internal Medicine stage B2 myxomatous mitral valve disease

Abstract Background Pimobendan might have favorable effects on renal function but this has not been well‐studied in dogs with myxomatous mitral valve disease (MMVD). Objectives Determine the effects of standard‐dose (SD_pimo) and high‐dose pimobendan (HD_pimo) on glomerular filtration rate (GFR) and cardiac size and function in dogs with preclinical MMVD. Animals Thirty nonazotemic dogs with stage B2 MMVD. Methods Prospective, randomized, double‐blinded, placebo‐controlled clinical study. Dogs had an echocardiographic examination, assessment of GFR (iohexol clearance), N‐terminal probrain natriuretic peptide (NT‐proBNP), and quality of life (QOL) score at baseline and 7 to 10 days after placebo (n = 6), SD_pimo 0.2 to 0.3 mg/kg q12 (n = 12), or HD_pimo 0.5 to 0.6 mg/kg q12h (n = 12). Results No significant differences in GFR or QOL scores were detected between groups (P ≥.07). After HD_pimo, the mean [SD] percent change of NT_proBNP (−46.1 [20.2]%), left atrial volume (LAV; −27.1 [16.9]%), left ventricular end‐diastolic volume (EDV; −21.8 [15.0]%), and end‐systolic volume (ESV; −55.0 [20.7]%) were significantly different (P ≤.004) from placebo (0.5 [19.9]%, 1.3 [15.6]%, −0.2 [8.2]%, −7.3 [35.6]%, respectively) but not the percent change after SD_pimo (−36.6 [16.1]%, −22.7 [14.9]%, −16.7 [12.5]%, −41.6 [14.8]%, respectively; P > .05). After SD_pimo, percent change of NT_proBNP, LAV, EDV, and ESV were significantly different from placebo (P < .05). Conclusions and Clinical Importance Results suggest that pimobendan (SD_pimo or HD_pimo) might not affect renal function in nonazotemic dogs with stage B2 MMVD. High‐dose pimobendan did not demonstrate advantages over SD_pimo within the constraints of our study.

[1]  J. Elliott,et al.  Clinical utility of estimation of glomerular filtration rate in dogs , 2019, Journal of veterinary internal medicine.

[2]  A. N. Sharpe,et al.  Echocardiographic quantitation of left heart size and function in 122 healthy dogs: A prospective study proposing reference intervals and assessing repeatability , 2019, Journal of veterinary internal medicine.

[3]  J. Häggström,et al.  ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs , 2019, Journal of veterinary internal medicine.

[4]  J. Häggström,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. , 2018, Journal of veterinary internal medicine.

[5]  T. Spillmann,et al.  Determination of iohexol in canine plasma - strong correlation between enzyme-linked immunosorbent assay, high-performance liquid chromatography, and neutron activation analysis , 2018 .

[6]  P. Brambilla,et al.  Preliminary Investigation of Cardiovascular–Renal Disorders in Dogs with Chronic Mitral Valve Disease , 2016, Journal of veterinary internal medicine.

[7]  G. Remuzzi,et al.  Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol? , 2016, Clinical kidney journal.

[8]  J. Devi,et al.  The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs. , 2016, Journal of veterinary pharmacology and therapeutics.

[9]  A. Levey,et al.  GFR as the "Gold Standard": Estimated, Measured, and True. , 2016, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[10]  C. Bussadori,et al.  Cardiovascular–renal axis disorders in the domestic dog and cat: a veterinary consensus statement , 2015, The Journal of small animal practice.

[11]  J. Elliott,et al.  The effects of storage conditions on measurements of canine N-terminal pro-B-type natriuretic peptide. , 2015, Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology.

[12]  J. Häggström,et al.  Short-term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive heart failure. , 2013, Journal of veterinary internal medicine.

[13]  J. Häggström,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. , 2013, Journal of veterinary internal medicine.

[14]  S. Werre,et al.  Effect of furosemide and high-dosage pimobendan administration on the renin-angiotensin-aldosterone system in dogs. , 2013, American journal of veterinary research.

[15]  T. DeFrancesco Management of cardiac emergencies in small animals. , 2013, The Veterinary clinics of North America. Small animal practice.

[16]  M. Borgarelli,et al.  Historical review, epidemiology and natural history of degenerative mitral valve disease. , 2012, Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology.

[17]  T. DeFrancesco,et al.  Effects of furosemide and the combination of furosemide and the labeled dosage of pimobendan on the circulating renin-angiotensin-aldosterone system in clinically normal dogs. , 2011, American journal of veterinary research.

[18]  R. Fukushima,et al.  The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation. , 2011, Journal of veterinary internal medicine.

[19]  B. Pressler,et al.  An overview of glomerular filtration rate testing in dogs and cats. , 2011, Veterinary journal.

[20]  L. Stevens,et al.  Measured GFR as a confirmatory test for estimated GFR. , 2009, Journal of the American Society of Nephrology : JASN.

[21]  T. DeFrancesco,et al.  Acute effect of pimobendan and furosemide on the circulating renin-angiotensin-aldosterone system in healthy dogs. , 2009, Journal of veterinary internal medicine.

[22]  M. Fusellier,et al.  Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs. , 2008, Journal of veterinary pharmacology and therapeutics.

[23]  M. Herrtage,et al.  Glomerular filtration rate estimated by 3-sample plasma clearance of iohexol in 118 healthy dogs. , 2008, Journal of veterinary internal medicine.

[24]  T. DeFrancesco,et al.  The effect of amlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone system in the dog. , 2007, Journal of veterinary pharmacology and therapeutics.

[25]  V. Chetboul,et al.  Azotemia and glomerular filtration rate in dogs with chronic valvular disease. , 2007, Journal of veterinary internal medicine.

[26]  R. Kano,et al.  Effects of pimobendan for mitral valve regurgitation in dogs. , 2007, The Journal of veterinary medical science.

[27]  Soo-Youn Lee,et al.  Determination of iohexol clearance by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[28]  P. Barthez,et al.  Simplified methods for estimation of plasma clearance of iohexol in dogs and cats. , 2006, Journal of veterinary internal medicine.

[29]  D. Finco Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of technetium Tc 99m pentetate and exogenous creatinine in dogs. , 2005, American journal of veterinary research.

[30]  A. Must,et al.  Development and evaluation of a questionnaire for assessing health-related quality of life in dogs with cardiac disease. , 2005, Journal of the American Veterinary Medical Association.

[31]  Jens Häggström,et al.  Allometric scaling of M-mode cardiac measurements in normal adult dogs. , 2004, Journal of veterinary internal medicine.

[32]  J. Häggström,et al.  Left atrial to aortic root indices using two-dimensional and M-mode echocardiography in cavalier King Charles spaniels with and without left atrial enlargement. , 2002, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[33]  T. DeFrancesco,et al.  Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation. , 2002, Journal of the American Veterinary Medical Association.

[34]  W. Braselton,et al.  Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs. , 2001, Journal of veterinary internal medicine.

[35]  H. Erb,et al.  Evaluation of four 2-dimensional echocardiographic methods of assessing left atrial size in dogs. , 2000, Journal of veterinary internal medicine.

[36]  R. Heiene,et al.  The relationship between some plasma clearance methods for estimation of glomerular filtration rate in dogs with pyometra. , 1999, Journal of veterinary internal medicine.

[37]  R. Heiene,et al.  Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog: a review. , 1998, Journal of veterinary internal medicine.

[38]  G. Trieb,et al.  Comparative cardiac toxicity of the i.v. administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs. , 1997, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[39]  J. Häggström,et al.  Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation. , 1996, American journal of veterinary research.

[40]  P. Pagel,et al.  Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs , 1996, British journal of pharmacology.

[41]  S. A. Brown,et al.  Evaluation of a single injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs. , 1996, American journal of veterinary research.

[42]  W. P. Thomas,et al.  Recommendations for standards in transthoracic two-dimensional echocardiography in the dog and cat. Echocardiography Committee of the Specialty of Cardiology, American College of Veterinary Internal Medicine. , 1993, Journal of veterinary internal medicine.