PDF(Pubmed)
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.
OBJECTIVE: 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.
METHODS: 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: 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.
OBJECTIVE: 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.
METHODS: 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: 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.
摘要：
背景：犬磷酸二酯酶（PDE）5A基因（PDE5A：E90K）中的一种变体与循环环磷酸鸟苷（cGMP）浓度降低和对PDE5抑制剂治疗的反应有关。Pimobendan是一种PDE抑制剂，推荐用于狗的某些阶段的粘液瘤性二尖瓣疾病（MMVD）的药物治疗。
目的：PDE5A:E90K多态性减弱匹莫苯对体外血小板聚集的抑制作用，并增加骑士王查尔斯猎犬（CKCS）的基础血小板聚集。选定的临床变量(MMVD严重程度，性别,年龄,血细胞比容,富血小板血浆[PRP]中的血小板计数，和超声心动图左心室缩短分数[LVFS]）将不显示与结果相关。
方法：52例私有CKCS，无MMVD或临床前MMVD。
方法：使用血液样本，我们使用Sanger测序和二磷酸腺苷诱导的血小板聚集反应（曲线下面积[AUC]，最大聚合[MaxA]，和速度[Vel]）使用透光聚合法，有和没有匹莫苯。狗也接受了超声心动图检查。
结果：匹莫苯丹抑制血小板功能，MaxA,和浓度为10μM的Vel(P<.0001)和0.03μM的Vel(P<.001)。PDE5A：E90K多态性不影响匹莫苯或基础血小板聚集反应的抑制作用。
结论：PDE5A:E90K多态性不影响CKCS的体外基础血小板聚集反应或匹莫苯对血小板聚集的抑制作用。具有PDE5A：E90K多态性的狗似乎没有改变血小板功能或对匹莫苯治疗的反应。
目的：PDE5A:E90K多态性减弱匹莫苯对体外血小板聚集的抑制作用，并增加骑士王查尔斯猎犬（CKCS）的基础血小板聚集。选定的临床变量(MMVD严重程度，性别,年龄,血细胞比容,富血小板血浆[PRP]中的血小板计数，和超声心动图左心室缩短分数[LVFS]）将不显示与结果相关。
方法：52例私有CKCS，无MMVD或临床前MMVD。
方法：使用血液样本，我们使用Sanger测序和二磷酸腺苷诱导的血小板聚集反应（曲线下面积[AUC]，最大聚合[MaxA]，和速度[Vel]）使用透光聚合法，有和没有匹莫苯。狗也接受了超声心动图检查。
结果：匹莫苯丹抑制血小板功能，MaxA,和浓度为10μM的Vel(P<.0001)和0.03μM的Vel(P<.001)。PDE5A：E90K多态性不影响匹莫苯或基础血小板聚集反应的抑制作用。
结论：PDE5A:E90K多态性不影响CKCS的体外基础血小板聚集反应或匹莫苯对血小板聚集的抑制作用。具有PDE5A：E90K多态性的狗似乎没有改变血小板功能或对匹莫苯治疗的反应。
