Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease

M. A. Oyama, P. F. Solter, C. L. Thorn, Joshua A Stern

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction An 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. Animals Six privately owned dogs. Materials and methods Dogs 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. Results Four 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 conclusions We 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.

Original languageEnglish (US)
Pages (from-to)211-217
Number of pages7
JournalJournal of Veterinary Cardiology
Volume19
Issue number3
DOIs
StatePublished - Jun 1 2017

Fingerprint

natriuretic peptides
Brain Natriuretic Peptide
Mitral Valve
Canidae
Dogs
Safety
dogs
Cyclic GMP
guanosine monophosphate
Natriuretic Peptides
Heart Failure
Guanosine Monophosphate
Injections
heart valve diseases
heart failure
Heart Diseases
Hemodynamics
injection
Urine
Pressure

Keywords

  • Degenerative mitral valve disease
  • Endocardiosis
  • Heart failure

ASJC Scopus subject areas

  • Physiology
  • veterinary(all)

Cite this

Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease. / Oyama, M. A.; Solter, P. F.; Thorn, C. L.; Stern, Joshua A.

In: Journal of Veterinary Cardiology, Vol. 19, No. 3, 01.06.2017, p. 211-217.

Research output: Contribution to journalArticle

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abstract = "Introduction An 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. Animals Six privately owned dogs. Materials and methods Dogs 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. Results Four 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 conclusions We 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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T1 - 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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AU - Stern, Joshua A

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N2 - Introduction An 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. Animals Six privately owned dogs. Materials and methods Dogs 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. Results Four 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 conclusions We 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.

AB - Introduction An 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. Animals Six privately owned dogs. Materials and methods Dogs 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. Results Four 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 conclusions We 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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KW - Endocardiosis

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