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Research article - Peer-reviewed, 2023

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

Reimann, Maria J.; Faisst, Daniel N.; Knold, Mads; Meurs, Kathryn M.; Stern, Joshua A.; Cremer, Signe E.; Moller, Jacob E.; Ljungvall, Ingrid; Haggstrom, Jens; Olsen, Lisbeth H.

Abstract

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 mu M (P <.0001) and Vel at 0.03 mu M (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.

Keywords

dogs; genetic variation; heart disease; light transmission aggregometry; pharmacogenetics; platelet inhibition

Published in

Journal of Veterinary Internal Medicine
2023, Volume: 37, number: 3, pages: 2145-2156
Publisher: WILEY