No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan-induced inhibition of platelet aggregation response

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Background: A variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs. Hypothesis: PDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet-rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results. Animals: Fifty-two privately owned CKCS with no or preclinical MMVD. Methods: Using blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate-induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography. Results: Pimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P <.0001) and Vel at 0.03 μM (P <.001). PDE5A:E90K polymorphism did not influence the inhibitory effect of pimobendan or basal platelet aggregation response. Conclusions and Clinical Importance: The PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.

TidsskriftJournal of Veterinary Internal Medicine
Udgave nummer6
Sider (fra-til)1947-2660
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The study was supported financially by research grants from the Independent Research Fund Denmark (Project no. 7017‐00131B), Thure F and Karin Forsberg's Foundation (Sweden; Project no. 2020‐03), University of Copenhagen Foundation for Scientific Studies in Companion Animals (Denmark; Project no. 2020‐0002) and Sveland Foundation (Sweden). Preliminary results were presented at the European College of Veterinary Internal Medicine – Companion Animals (ECVIM‐CA) 31st Annual Online Congress, 1‐4 September 2021. Authors thank Marianne Kjestine Petersen, Silas Alexander Hovmand, and Carl Sichlau Bruun at the Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark, and Nicole DeBruyne at the Department of Clinical Sciences, North Caroline State University, US for excellent technical assistance.

Publisher Copyright:
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

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