Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish
Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish
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DOI：
10.1371/journal.pone.0232457
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发表时间：
2020-05-13
期刊：
影响因子：
3.7
通讯作者：
Xu, Xiaolei
中科院分区：
文献类型：
--
作者：
Yan, Jianhua;Li, Hongsong;Xu, Xiaolei
由于其强大的遗传学，成年斑马鱼越来越多地被用于研究心血管疾病。考虑到这种脊椎动物在常温下的心率接近每分钟100次，非常接近人类，我们评估了使用这种脊椎动物来模拟窦性心跳骤停(SA)和病态窦房结综合征(SSS)等心律紊乱的情况。我们首先优化了一种测量成年斑马鱼心电图的方案。我们确定了探头的位置，实施了开胸显微外科手术，测量了温度的影响，并确定了合适的麻醉剂量和时间。然后，我们提出了一个超过1.5秒的PP间隔作为一个任意的标准来定义常温下成年鱼的SA发作，这是基于目前人类SA发作的定义与我们对老化的野生型鱼类和TG(SCN5A-D1275N)鱼(遗传SSS的鱼类模型)候选SA发作的研究的比较。根据这一标准，约5%的野生型鱼亚群可被认为有SA发作，这一比例在3岁鱼中显著增加到约25%。作为对阿托品的反应，这个亚群既有与TG(SCN5A-D1275N)模型相同的SSS表型特征，如心动过缓，也有独特的SSS表型特征，如QRS/P比值增加和变时性不全。总之，这项研究定义了成年斑马鱼的基线SA和SSS，并强调了使用斑马鱼作为研究与衰老相关的SSS的替代模型。
Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of similar to 100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.