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Abstract：
BACKGROUND: Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH.
OBJECTIVE: Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation.
METHODS: Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH.
METHODS: Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA.
RESULTS: Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups.
CONCLUSIONS: Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.
OBJECTIVE: Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation.
METHODS: Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH.
METHODS: Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA.
RESULTS: Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups.
CONCLUSIONS: Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.
摘要：
背景：患有黏液性二尖瓣疾病（MMVD）的狗的肺动脉高压（PH）是由肺静脉压升高引起的。血栓形成,血管重塑,血小板介导的血管收缩可加剧PH。
目的：患有PH的狗将表现出高凝状态，以血小板活化增加为特征，血小板-白细胞，和血小板中性粒细胞聚集形成。
方法：11只诊断为MMVD和PH的狗（≥3.5kg）和10只诊断为缺乏PH的MMVD的狗。
方法：前瞻性队列离体研究。所有的狗都接受了超声心动图检查，CBC,三视图胸片，和心丝虫抗原检测。通过超声心动图评估PH和MMVD的严重程度。使用血栓弹力图（TEG）评估凝血的粘弹性监测。使用流式细胞术评估血小板活化和血小板-白细胞/血小板-中性粒细胞相互作用。通过ELISA测量血浆5-羟色胺浓度。
结果：来自具有MMVD和PH的狗的未刺激血小板比MMVD对照表达更多的表面P-选择素（P=0.03）。来自具有MMVD和PH的狗的血小板具有响应于激动剂的持续激活。与MMVD对照组相比，MMVD和PH犬的血小板-白细胞聚集体数量更高（P=0.01）。全血的离体刺激在具有MMVD和PH的狗中导致较高数量的血小板-嗜中性粒细胞聚集体(P=0.01)。根据TEG或血浆5-羟色胺浓度评估高凝状态在两组之间没有差异。
结论：在MMVD和PH的狗中出现血小板高反应性和增加的血小板-中性粒细胞相互作用，提示血小板在PH的发病机制中起作用。抗血小板药物在MMVD和PH犬中的临床益处需要进一步研究。
目的：患有PH的狗将表现出高凝状态，以血小板活化增加为特征，血小板-白细胞，和血小板中性粒细胞聚集形成。
方法：11只诊断为MMVD和PH的狗（≥3.5kg）和10只诊断为缺乏PH的MMVD的狗。
方法：前瞻性队列离体研究。所有的狗都接受了超声心动图检查，CBC,三视图胸片，和心丝虫抗原检测。通过超声心动图评估PH和MMVD的严重程度。使用血栓弹力图（TEG）评估凝血的粘弹性监测。使用流式细胞术评估血小板活化和血小板-白细胞/血小板-中性粒细胞相互作用。通过ELISA测量血浆5-羟色胺浓度。
结果：来自具有MMVD和PH的狗的未刺激血小板比MMVD对照表达更多的表面P-选择素（P=0.03）。来自具有MMVD和PH的狗的血小板具有响应于激动剂的持续激活。与MMVD对照组相比，MMVD和PH犬的血小板-白细胞聚集体数量更高（P=0.01）。全血的离体刺激在具有MMVD和PH的狗中导致较高数量的血小板-嗜中性粒细胞聚集体(P=0.01)。根据TEG或血浆5-羟色胺浓度评估高凝状态在两组之间没有差异。
结论：在MMVD和PH的狗中出现血小板高反应性和增加的血小板-中性粒细胞相互作用，提示血小板在PH的发病机制中起作用。抗血小板药物在MMVD和PH犬中的临床益处需要进一步研究。
