Feasibility,safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease |
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| Authors: | MA Oyama PF Solter CL Thorn JA Stern |
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| Institution: | 1. Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St., Philadelphia, 19104, PA, USA;2. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Dr., Philadelphia, 19104, PA, USA;3. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, 3400 Civic Center Blvd., Philadelphia, 19104, PA, USA;4. Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Ave. Urbana, 61802, IL, USA;5. Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, One Shields Ave., Davis, 95616, CA, USA |
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| Abstract: | IntroductionAn important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3′,5′-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs.AnimalsSix privately owned dogs.Materials and methodsDogs were enrolled in a modified 3 + 3 phase I trial. Three dogs initially received doses of 2.5 and 5 μg/kg SC syncBNP followed by an additional three dogs dosed at 5 and 10 μg/kg. Hemodynamic monitoring was performed for 120 min after each injection. Blood and urine samples were collected at 45 and 120 min after injection of 5 μg/kg. Major adverse clinical events that would potentially halt testing were pre-defined.ResultsFour healthy dogs and two dogs with stage B1 mitral valve disease were recruited. Synthetic canine B-type natriuretic peptide was well tolerated at all doses. Synthetic canine B-type natriuretic peptide at 5 μg/kg significantly increased median plasma cGMP (baseline cGMP, 131.5 pmol/mL range, 91.9–183.6 pmol/mL]; 45 min, 153.6 pmol/mL 140.3–214.3 pmol/mL]; 120 min, 192.7 pmol/mL 139.1–240.1 pmol/mL]; p=0.041).Discussion and conclusionsWe report for the first time administration of syncBNP in privately owned dogs. Administration of SC syncBNP was feasible, well tolerated, safe, and increased plasma cGMP concentration. Further studies using exogenous syncBNP for treatment of heart disease are warranted. |
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| Keywords: | Degenerative mitral valve disease Endocardiosis Heart failure |
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