Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510, Japan.
J Pharmacol Sci. 2024 Sep;156(1):19-29. doi: 10.1016/j.jphs.2024.06.004. Epub 2024 Jun 27.
To characterize utility of atrioventricular block (AVB) dogs as atrial fibrillation (AF) model, we studied remodeling processes occurring in their atria in acute (<2 weeks) and chronic (>4 weeks) phases. Fifty beagle dogs were used. Holter electrocardiogram demonstrated that paroxysmal AF occurred immediately after the production of AVB, of which duration tended to be prolonged in chronic phase. Electrophysiological analysis showed that inter-atrial conduction time and duration of burst pacing-induced AF increased in the chronic phase compared with those in the acute phase, but that atrial effective refractory period was hardly altered. Echocardiographic study revealed that diameters of left atrium, right pulmonary vein and inferior vena cava increased similarly in the acute and chronic phases. Histological evaluation indicated that hypertrophy and fibrosis in atrial tissue increased in the chronic phase. Electropharmacological characterization showed that i.v. pilsicainide effectively suppressed burst pacing-induced AF with increasing atrial conduction time and refractoriness of AVB dogs in chronic phase, but that i.v. amiodarone did not exert such electrophysiological effects. Taken together, AVB dogs in chronic phase appear to possess such pathophysiology as developed in the atria of early-stage AF patients, and therefore they can be used to evaluate drug candidates against early-stage AF.
为了描述房室传导阻滞(AVB)犬作为心房颤动(AF)模型的效用,我们研究了其心房在急性(<2 周)和慢性(>4 周)阶段发生的重塑过程。使用了 50 只比格犬。动态心电图显示,AVB 后立即发生阵发性 AF,其持续时间在慢性期趋于延长。电生理分析表明,与急性期相比,慢性期的房间隔传导时间和burst 起搏诱导的 AF 持续时间增加,但心房有效不应期几乎没有改变。超声心动图研究显示,左心房、右肺静脉和下腔静脉的直径在急性和慢性阶段均相似增加。组织学评估表明,心房组织的肥厚和纤维化在慢性期增加。电药理学特征表明,静脉注射普司卡因可有效抑制慢性期 AVB 犬的burst 起搏诱导的 AF,同时增加心房传导时间和不应性,但静脉注射胺碘酮则不能发挥这种电生理作用。综上所述,慢性期的 AVB 犬似乎具有与早期 AF 患者心房中发展的病理生理学相似的特征,因此可用于评估针对早期 AF 的候选药物。