Name: multi-system monitoring for identification of seizures, arrhythmias and apnea in conscious restrained rabbits
Uploaded: 2021-03-27T13:00:00
Description: Watch this Scientific Journal Video about Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits at JoVE.com

作者承认这项研究得到了美国心脏协会、美国癫痫学会和SUNY上州市药理学系的资助。

所有实验都是按照国家卫生研究院（NIH）指南和上州立大学机构动物护理和使用委员会（IACUC）进行的。此外，本议定书的大纲在 图1中提供。
1. 准备录音设备
<ol><li>将计算机连接到带有 64 针头箱的放大器。 注意：每只动物有四个直皮下头皮销电极（7或13毫米），用于头部4个象限的EEG， ECG（埃因托芬三角形）3个弯曲的皮?...

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这种实验设置有助于在兔子中，特别是在心脏和/或神经元疾病模型中，提供详细的同步视频-EEG-ECG-氧化-量谱记录和分析。本文结果表明，该方法能够检测癫痫发作和心律失常，并区分它们与电图文物。给兔子一个刺激性，诱导癫痫发作时，会得出预期的结果。从视频 EEG 录音中获得的数据能够进一步分析，以区分自愿运动与电机癫痫发作和脑电图异常（包括幻觉驱动反应、脑病和癫痫放电）的日...

心电图 （ECG） 经常用于临床设置，以评估心脏导电和电激活恢复过程的动态。心电图对于检测、本地化和评估心律失常、缺血和梗塞的风险非常重要。通常，电极贴在患者的胸部、手臂和腿部，以便提供心脏的三维视图。当心肌去极化的方向朝向电极时产生正偏转，当心肌去极化方向远离电极时产生负偏转。心脏周期的电图成分包括心房去极化（P波）、心房-心室传导（P-R间隔）、心室兴奋（QRS复合体）和心室再极化（T波）。在心电图和行动潜力措施方面，许多哺乳动物，包括人类，兔子，狗，豚鼠，猪，山羊和马1，2，3有很大的相似之处。
兔子是心脏转化研究的理想模式。兔子心脏在离子通道组成方面与人的心脏相似，其作用潜力属性为2、4、5。兔子已经用于生成遗传，获得和药物诱导的心脏病模型2，4，6，7，8。在心脏心电图和行动的潜在反应药物在人类和兔子7，10，11有很大的相似之处。
与兔子、人类和其他大型哺乳动物12、13、14相比，啮齿动物的心率和心脏电激活恢复过程大不相同。啮齿动物的心脏跳动速度是人类的10倍。相比之下，与人类和兔子心电图中的等离子电ST段相比，啮齿动物14、15、16没有ST段。此外，啮齿动物有一个QRS-r'波形与倒T波14，15，16。QT间隔的测量结果与14、15、16的啮齿动物与人和兔子的QT间隔非常不同。此外，正常的心电图值在人类与啮齿动物12，15，16有很大的不同。心电图波形的这些差异可归因于作用潜在形态和离子通道的差异，驱动心脏再极化9，14。虽然瞬态向外钾电流是啮齿动物短（非圆顶）心脏运动潜在形态的主要再极化电流，但在人类和兔子中，在行动潜力上有一个大的相-2圆顶，而延迟的整流器钾电流（IKr和IKs）是人类和兔子4、9、13、17的主要再极化电流。重要的是，IKr和IKs在啮齿动物中是不存在/最小表达的，由于IKr和IKs的时态激活动力学，它在心脏作用潜在形态9，13中没有作用。因此，兔子提供了一个更转化的模型，以评估药物诱导，获得和遗传心电图异常和心律失常4，7，13的机制。其次，由于许多研究表明，在原发性心脏（长QT综合征18、19、20）或神经元疾病（癫痫21、22、23、24）中都存在神经元和心脏电异常，因此研究动物模型中密切再现人类生理学的基本机制非常重要。虽然啮齿动物可能足以模拟人脑，但啮齿动物并不是人类心脏生理学的理想模型。
脑电图 （EEG） 使用电极（通常放置在头皮上或颅内）来记录皮质电功能。这些电极可以检测大脑皮层25中附近金字塔神经元群的发射速率和同步性的变化。这些信息可用于评估大脑功能和清醒/睡眠状态。此外，EEG有助于定位癫痫活性，并区分癫痫发作与非癫痫事件（例如，心理非癫痫活性和心性事件）。为了诊断癫痫类型、发人深省因素和癫痫发作的来源，癫痫患者受到各种可能带来癫痫发作的动作。各种方法包括过度通风、色情刺激和睡眠不足。该协议表明，使用色情刺激诱导EEG畸变和癫痫发作的兔子26，27，28，29。
同时视频-EEG-ECG录音已广泛用于人类和啮齿动物，以评估行为，神经元和心脏活动在前，ictal，和后ictal状态30。虽然多项研究已分别在兔子4、31、32、33中进行电子EG和心电图录音，但一个在有意识的克制兔子中获取和分析同步视频EEG-ECG的系统尚未建立。本文描述了一个协议的设计和实施，该协议可以同时记录有意识兔子的视频-EEG-ECG-capn1x-氧化测量数据，以评估神经-心脏电和呼吸功能。从这种方法中收集的结果可以表明心律失常、癫痫发作、呼吸障碍和身体表现之间的易感性、触发因素、动力学和和谐。我们的实验系统的一个优点是，我们获得有意识的录音，而无需镇静剂。兔子在约束器中停留≥5小时，移动最少。麻醉师干扰神经元、心脏、呼吸和自主功能，意识状态下的录音提供最多的生理数据。
此记录系统可能最终提供详细的见解，以增进对癫痫突发意外死亡的神经、心脏和呼吸机制的理解（SUDEP）。除了上述神经和心脏监测外，最近的证据也支持了呼吸衰竭作为癫痫发作后突然死亡的潜在贡献的作用。为了监测兔子的呼吸状况，在癫痫发作前、发作期间和发作后进行了牛科和角图测量，以评估呼吸系统的状况。这里提出的协议旨在评估药理学和磷刺激诱发兔子发作的阈值。此协议可以检测可能导致物理表现的细微的 EEG 和 ECG 异常。此外，该方法还可用于新型药物和器械的心脏安全和抗心律失常功效测试。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>0.9% Sodium Chloride Irrigation, USP - Flexible Container</td>
			<td>PFIZER (HOSPIRA)</td>
			<td>7983-09</td>
			<td>Dilutant</td>
		</tr>
		<tr>
			<td>10cc Luer Lock syringe with 20G x 1&#34; Needle</td>
			<td>Sur-Vet</td>
			<td>SS-10L2025</td>
			<td>Used as a flush after drug injection</td>
		</tr>
		<tr>
			<td>4x4 gauze sponges</td>
			<td>Fisher Scientific</td>
			<td>22-415-469</td>
			<td>Rolled in a tube to splint ear with angiocatheter</td>
		</tr>
		<tr>
			<td>Apple Sauce</td>
			<td>Kirkland</td>
			<td>897971</td>
			<td>Vehicle for oral medications</td>
		</tr>
		<tr>
			<td>Computer</td>
			<td>Dell</td>
			<td>Optiplex 5040</td>
			<td>Acquisition computer</td>
		</tr>
		<tr>
			<td>E-4031</td>
			<td>Tocris</td>
			<td>1808</td>
			<td>Agent known to prolong the QT interval</td>
		</tr>
		<tr>
			<td>ECG Electrode</td>
			<td>RhythmLink</td>
			<td>RLSND116-2.5</td>
			<td>13mm 35-degree bent (0.4 mm diameter) subdermal pin electrodes</td>
		</tr>
		<tr>
			<td>EEG Electrode</td>
			<td>RhythmLink</td>
			<td>RLSP513</td>
			<td>5-twist 13mm straight (0.4mm diameter) subdermal pin electrodes</td>
		</tr>
		<tr>
			<td>EEGLAB (2020)</td>
			<td>Swartz Center for Computational Neuroscience</td>
			<td>Open Access</td>
			<td>Can perform spectral analysis of EEG</td>
		</tr>
		<tr>
			<td>Ethernet-to-ethernet adapter</td>
			<td>Linksys</td>
			<td>USB3G16</td>
			<td>Adapter for connecting the camera to the computer</td>
		</tr>
		<tr>
			<td>Euthanasia-III Solution</td>
			<td>Med-Pharmex</td>
			<td>ANADA 200-280</td>
			<td>Contains pentobarbital sodium and phenytoin sodium, controlled substance</td>
		</tr>
		<tr>
			<td>Foam padding</td>
			<td>Generic</td>
			<td>N/A</td>
			<td>Reduces pressure applied to the neck of small rabbits by the restrainer in order to prevent the adverse cardiorespiratory effects of neck compression</td>
		</tr>
		<tr>
			<td>Heparin Lock Flush</td>
			<td>Medline</td>
			<td>EMZ50051240</td>
			<td>To maintain patency of angiocatheter</td>
		</tr>
		<tr>
			<td>IR Light</td>
			<td>Bosch</td>
			<td>EX12LED-3BD-8W</td>
			<td>Facilitates recordings in the dark</td>
		</tr>
		<tr>
			<td>LabChart Pro (2019, Version 8.1.16)</td>
			<td>ADInstruments</td>
			<td>N/A</td>
			<td>ECG Analysis</td>
		</tr>
		<tr>
			<td>JELCO PROTECTIV Safety I.V. Catheters, 25 gauge</td>
			<td>Smiths Medical</td>
			<td>3060</td>
			<td>Used to catherize marginal ear vein</td>
		</tr>
		<tr>
			<td>MATLAB (R2019b, Update 5)</td>
			<td>MathWorks</td>
			<td>N/A</td>
			<td>Required to run EEGLAB</td>
		</tr>
		<tr>
			<td>Microphone</td>
			<td>Sony Stereo</td>
			<td>ECM-D570P</td>
			<td>Recording of audible manifestions of seizures</td>
		</tr>
		<tr>
			<td>Micropore Medical Tape, Paper, White</td>
			<td>3M</td>
			<td>1530-1</td>
			<td>Used to secure wires and create ear splint</td>
		</tr>
		<tr>
			<td>Natus NeuroWorks</td>
			<td>Natus</td>
			<td>LC101-8</td>
			<td>Acquisition and review software</td>
		</tr>
		<tr>
			<td>Pentylenetetrazol (1 - 10 mg/kg always in 1mL volume)</td>
			<td>Sigma-Aldrich</td>
			<td>88580</td>
			<td>Dilutions prepared in saline</td>
		</tr>
		<tr>
			<td>Photic Stimulator</td>
			<td>Grass</td>
			<td>PS22</td>
			<td>Stimulator to control frequency, delay, duration, intensity of the light pulses</td>
		</tr>
		<tr>
			<td>Plastic wire organizer / bundler</td>
			<td>12Vwire.com</td>
			<td>LM-12-100-BLK</td>
			<td>Bundle wires to cut down on noise</td>
		</tr>
		<tr>
			<td>PS 22 Photic Stimulator</td>
			<td>Grass Instruments</td>
			<td>BZA641035</td>
			<td>Strobe light with adjustable flash frequency, delay, and intensity</td>
		</tr>
		<tr>
			<td>PVC pipe</td>
			<td>Generic</td>
			<td>N/A</td>
			<td>Prevents small rabbits from kicking their hind legs and causing spinal injury</td>
		</tr>
		<tr>
			<td>Quantum Amplifier</td>
			<td>Natus</td>
			<td>13926</td>
			<td>Amplifier / digitizer</td>
		</tr>
		<tr>
			<td>Quantum HeadBox Amplifier</td>
			<td>Natus</td>
			<td>22134</td>
			<td>64-pin breakout box</td>
		</tr>
		<tr>
			<td>Rabbit Restrainer</td>
			<td>Plas-Labs</td>
			<td>501-TC</td>
			<td>Various size rabbit restrainers are available. 6&#34; x 18&#34; x 6&#34; in this study.</td>
		</tr>
		<tr>
			<td>Rubber pad (booster)</td>
			<td>Generic</td>
			<td>N/A</td>
			<td>Raises small rabbits up in the restrainer to prevent neck compression</td>
		</tr>
		<tr>
			<td>SpO2 ear clip</td>
			<td>NONIN</td>
			<td>61000</td>
			<td>PureSAT/SpO2</td>
		</tr>
		<tr>
			<td>SpO2 sensor adapter</td>
			<td>NONIN</td>
			<td>13931</td>
			<td>XPOD PureSAT/SpO2</td>
		</tr>
		<tr>
			<td>SRG-X120 1080p PTZ Camera with HDMI, IP &#38; 3G-SDI Output</td>
			<td>Sony</td>
			<td>SRG-X120</td>
			<td>Impela Camera</td>
		</tr>
		<tr>
			<td>Terumo Sur-Vet Tuberculin Syringe 1cc 25G X 5/8&#34; Regular Luer</td>
			<td>Sur-Vet</td>
			<td>13882</td>
			<td>Used to inject intravenous medications</td>
		</tr>
		<tr>
			<td>Veterinary Injection Plug Luer Lock</td>
			<td>Sur-Vet</td>
			<td>SRIP2V</td>
			<td>Injection plug for inserting the needle for intravenous medication</td>
		</tr>
		<tr>
			<td>Webcol Alcohol Prep, Sterile, Large, 2-ply</td>
			<td>Covidien</td>
			<td>5110</td>
			<td>To prepare ear vein before catheterization</td>
		</tr>
	</tbody>
</table>

multi-system monitoring for identification of seizures, arrhythmias and apnea in conscious restrained rabbits

离子通道病患者有发生癫痫发作和致命心律失常的高风险。癫痫患者（即癫痫心脏）的心脏病和心律失常患病率较高。此外，心脏和自主障碍已报告围绕癫痫发作。1：1，000 癫痫患者/年死于癫痫突发死亡 （SUDEP）。苏迪普的机制仍然不完全了解。脑电图 （EEG） 和心电图 （ECG） 是临床环境中经常使用的两种技术，用于检测和研究癫痫发作和心律失常的基板/触发器。虽然许多研究和描述这种方法是在啮齿动物，他们的心脏电活动与人类显著不同。本文描述了一种非侵入性方法，用于记录有意识的兔子同时录制视频-EEG-ECG-氧化术- capns。由于心脏电功能在兔子和人类中相似，兔子提供了一个很好的转化诊断和治疗研究模型。除了概述数据采集的方法外，我们还讨论了研究兔子神经-心脏电功能和病理学的分析方法。这包括心律失常检测、脑电表光谱分析以及为受约束的兔子开发的癫痫发作量表。

上述方法能够检测大脑和心脏传导系统中的异常以及呼吸障碍。数据采集软件用于评估心电图形态并检测任何异常心率、传导障碍或心电图节律（心室/心室异位跳动和 Brady-/tachy-心律失常）（图 6）。除了可视化心电图形态外，还分析这些痕迹以量化 RR 间隔、心率、PR 间隔、P 持续时间、QRS 间隔、QT 间隔、QTc、JT 间隔和 T峰值 到 T端 ...

Watch this Scientific Journal Video about Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits at JoVE.com

Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits

我们利用同时进行的视频-EEG-ECG-氧化-量谱-封盖术，开发了一种评估兔子模型易感性的方法，以开发引起心律失常和癫痫发作。这种新型记录系统建立了一个平台，以测试治疗的功效和安全性，并可以捕捉复杂的多系统事件级联，最终导致突然死亡。

意识约束兔子中癫痫发作、心律失常和呼吸暂停的多系统监测

Patients with ion channelopathies are at a high risk of developing seizures and fatal cardiac arrhythmias. There is a higher prevalence of heart disease ...

心脏和呼吸功能障碍导致癫痫发作后突然死亡。因此，为了研究这种现象，在兔子模型上应用了多系统的方法。该技术能够同时监测和后期分析多只兔子的神经、心脏和呼吸功能，这些兔子围绕癫痫发作、心律失常和死亡前。虽然疾病可能主要是神经元或心脏，但它可能包括大脑和心脏的电干扰，如癫痫发作和心律失常，以及呼吸功能障碍。和兔子一起工作可能很困难，因为它们的后腿力量。移动兔子时和安装监视器时，注意保持兔子的平静。首先，将计算机连接到带有 64 针头箱的放大器。要使头箱上的每八个引脚成为参考，请将参考电极设置为独立。对于心电图电极的植入，将兔子固定在超平位置，头部位于调查员的膝盖上，低于其身体的其他部位。随着第二个调查员将毛皮展开以暴露底层皮肤，下皮将 35 度角弯曲的电极插入每个轴线中。位置引线在胸部，后到右前和左前肢。在腹部，前肢到左后肢。然后将地面销电极前部放在腹部右后肢。当所有心电图导线都正确放置后，用动物的后肢将兔子固定在适当大小的约束器中。使用 45 度角方法，将皮下直针电极插入头皮。将一个 EEG 引头放在右前部、左前部、右腹管和头部左腹部位。并将中央参考引线放在其他四个引线之间的中心点。将耳朵之间的电线运行，并松散地将其系在头部后面的约束器上。为了监测实验期间的呼吸，在边缘耳静脉上将脉冲氧化计连接到一只耳朵上，并轻轻地用帽管固定动物的嘴和鼻子上的面罩。然后将管子的另一端连接到生命体征监视器上。要录制视频 EEG-ECG，打开一个适当的市售 EEG 软件程序并调整视频，以便在视场内观察到所有兔子。为动物进行至少10至20分钟的基线记录，或直到心率稳定到每分钟200至250次，至少5分钟。将低频滤光片设置为一赫兹，将高频滤波器设置为 59 赫兹。实时添加锁定时间的笔记，以指示干预、神经-心脏事件以及运动或调查员人工制品的时间。对于photic刺激，将带圆形反射器的光源放在兔子面前30厘米，将闪光强度设置为最大。在头部两侧放置两面镜子，在兔子后面放置一面镜子，使光线进入兔子的眼睛。将光连接到具有可调速率、强度和持续时间的控制器上。随着菲色刺激器设置为一个赫兹和闪光灯，记录的反应30秒。用面具遮住兔子的眼睛，模拟或导致眼睛闭合，再刺激30秒。在记录眼睛睁开和眼睛闭合反应后，关闭刺激器30秒，并将控制器设置为下一个频率设置。在以两赫兹间隔从一个频率录制到 25 赫兹的频率后，以五赫兹增量将频率从 60 降至 25 赫兹，并以睁开眼睛记录 30 秒，闭着眼睛记录 30 秒。实验结束时，从兔子身上取出EEG和心电图引线，将动物送回家中的笼子里，由饲养人员进行日常护理。在服药之前，从未经治疗的兔子收集10至20分钟的基线EEG-ECG视频，如图所示。对于感兴趣的药物的口服管理，将每公斤感兴趣的药物混合0.3毫克，放入三毫升食品级苹果酱中，并将混合物装入三毫升口服注射器中。轻轻地抬起兔子的上唇，将注射器的尖端滑入被兔子牙齿遮挡的嘴边，并将整卷补充药物的苹果酱注射到兔子的嘴里。然后收集两个小时的 EEG-ECG 视频数据，然后将兔子送回其家庭笼子进行常规护理。在记录 EEG-ECG 对静脉注射药物管理的反应之前，剃掉兔子耳朵的后表面，使用 70% 的乙醇对部位进行消毒，并扩张边缘耳静脉。小心翼翼，用25口径的血管解剖器调节边缘耳静脉，并在导管末端放置注射塞。将三块卷纱布制成的夹板粘在耳朵上，以固定导管到位并直立保持耳朵。每毫升肝素盐水注射1毫升10个USP单位，以保持导管专利。基线记录完成后，每10分钟向导管注射一至10毫克感兴趣的药物，补充盐水。每次剂量后，仔细监测视频 EEG-ECG、氧化量谱、任何神经、心脏、电和呼吸异常或癫痫活动的视觉证据。实时以及后期分析期间注意这些变化。要分析心电图视频，请使用适当的市售软件来识别心电图数据中的心动过速、胸腺痛、异位跳动或其他心律失常的时期。为了减少要审查的数据量，创建一个塔乔格拉姆，以增加识别心动过速、心动过速或RR间隔不规则的易用性。有关药物管理实验后的视频 EEG 分析，可通过 EEG 跟踪进行视觉滚动，以区分癫痫与非癫痫运动，每次剂量药物后至少一分钟。对于幻影刺激实验后的视频 EEG 分析，在适当的 EEG 分析软件程序中创建光谱分析图。然后分析 EEG 的腹射引线，以预测是否存在和缺乏腹射驱动节奏。腹腔驱动节奏将在光谱分析中创建一个峰值，与刺激器的频率相对应。ECG 形态评估允许检测异常心率、传导和心电图波形式。这些痕迹还可用于量化心率、RR间隔、PR间隔、P 持续时间、QRS 间隔、QT 间隔、QTc、JT 间隔和 T 峰到 T 端间隔。来自腹外 EEG 引线的记录通常显示的振幅高于前引线数据的振幅。所有引线的主导频率通常以增量范围进行测量。在这里，从一个有代表性的兔子实验的睡眠主轴波显示。一段睡眠期的多个脑电油蒙太奇表明，这些波来自头部中心，这与人类的发现是一致的。除了正常的 EEG 变化外，在基线记录中还可以观察到各种有意识的非癫痫兔子运动，这些记录可用于区分这些数据和癫痫排泄物。重要的是将心电图引线安全地放入皮肤中，以保持电线远离腿部，并注意将兔子转移到约束器时电极是否仍然连接。这种多系统记录设备将使未来的药物安全性和疗效研究，并有助于全面了解各种已获得和遗传的疾病。该技术捕获癫痫发作后潜在的致命多组织功能障碍的过程，这将导致对SUDEP机制的更好理解。

Research

JoVE Journal

Medicine

Hyperinsulinemic-Euglycemic Clamp in the Conscious Rat

在自觉大鼠高胰岛素 - 正常血糖钳

Type 2 diabetes (T2D) is rapidly rising in prevalence. Characterized by either inadequate insulin production or the inability to utilize insulin produced, ...

科研

医学

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

心电图心脏风险评价指标和乌头碱诱发大鼠心律失常的易感性继癫痫持续状态的方法

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily ...

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

在自觉的，奔放的小鼠正常血糖高胰岛素 - 夹钳

Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or insulin clamp, is widely considered the "gold ...

Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases

生产用锌指核酸载脂蛋白C-III淘汰赛兔

Apolipoprotein (Apo) C-III (ApoCIII) resides on the surface of plasma chylomicron (CM), very low density lipoprotein (VLDL) and high density lipoproteins ...

Transcutaneous Assessment of Renal Function in Conscious Rodents

在鼠害自觉肾功能的评估皮

Glomerular filtration rate (GFR) is the gold standard to assess overall kidney function. However, traditional methods to evaluate GFR are cumbersome and ...

A Step by Step Protocol for Subretinal Surgery in Rabbits

一种用于兔视网膜下手术分步协议

Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in ...

Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits

糖尿病家兔欣德肢体缺血的临床前模型

Peripheral vascular disease is a widespread clinical problem that affects millions of patients worldwide. A major consequence of peripheral vascular ...

Blind Endotracheal Intubation in Neonatal Rabbits

新生儿兔子的盲内窥管插管

The newborn rabbit is a useful animal model for various pathologies and procedures. Airway management of the rabbit is complex due to its anatomical ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

植入遥测心电图和血压递质组合以确定意识小鼠的自发压力反射敏感性

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

分析长期心电图记录以检测小鼠心律失常

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...