经食管心房爆破起搏在大鼠心房颤动诱导中的应用
Summary
本工作描述了一种经食管心房爆裂起搏的实验方案，用于有效诱导大鼠心房颤动（AF）。该方案可用于具有健康或重塑心脏的大鼠，允许研究AF病理生理学，鉴定新的治疗靶点以及评估新的治疗策略。
Abstract
动物研究为我们理解心房颤动（AF）病理生理学和治疗管理带来了重要的见解。再入是心房颤动发病机制的主要机制之一，需要一定数量的心肌组织才能发生。由于心房面积小，啮齿动物长期以来一直被认为是对心房颤动的“抗性”。虽然自发性心房颤动已被证明发生在大鼠身上，但这些模型中发生心律失常需要长期随访（长达50周）。本工作描述了一种经食管心房爆裂起搏的实验方案，用于快速有效地诱导大鼠心房颤动。该方案可以成功地用于具有健康或重塑心脏的大鼠，在存在各种危险因素的情况下，允许研究心房颤动病理生理学，鉴定新的治疗靶点，以及评估新的预防和/或治疗策略。
Introduction
心房颤动 （AF） 是临床实践中最常见的持续性心律失常，其发病率和患病率在世界范围内继续急剧增加1.根据最近的研究，这种心律失常影响高达4%的世界人口2。然而，鉴于阵发性心房颤动可能无症状，因此可能无法逃脱检测，心房颤动的真实患病率可能远高于文献中提出的患病率。
心房颤动的病理生理学已被深入研究。然而，这种复杂性心律失常的潜在机制仍然不完全阐明，这反映在有限的治疗方案中，疗效值得怀疑。动物研究为我们理解心房颤动病理生理学和治疗管理带来了重要的见解。再入是AF发病机制3的主要机制之一，需要一定数量的心肌组织才能发生。因此，大型动物在心房颤动研究中通常是首选，而由于其心房面积小，啮齿动物长期以来一直被认为对心房颤动具有“抗性”。然而，大型动物的使用主要受到处理困难的阻碍。同时，尽管自发性心房颤动已被证明发生在大鼠4中，但需要长期随访（长达50周）才能在这些模型中发生心律失常5。还开发了确保小型啮齿动物快速发生心房颤动的模型。大多数情况下，这些模型使用急性电刺激，通常在存在其他有利条件的情况下，例如伴随的副交感神经刺激或窒息，以人为诱导心房颤动6，7。尽管这些模型有效，但无法评估心房颤动相关的关键特征，例如心房的进行性电、结构、自主神经或分子重塑，也无法评估常规或非常规抗心律失常药物对心房底物或室性心律失常风险的影响8，9。
本工作描述了一种长期经食管心房爆裂起搏的实验方案，用于快速有效地诱导大鼠心房颤动。该方案适用于急性和长期研究，并且可以在存在各种危险因素的情况下成功用于具有健康或重塑心脏的大鼠，从而可以研究AF病理生理学，鉴定新的治疗靶点以及评估新的预防和/或治疗策略。
Protocol
Representative Results
Discussion
本文描述了一种长期经食管心房爆裂起搏的实验方案，用于快速有效地诱导大鼠心房颤动，适用于急性和长期心房颤动研究。本文描述的10天刺激方案已成功用于开发“继发性自发性心房颤动模型”（即，在通过电刺激诱导AF一段时间后，心房颤动自发发展的模型）10。然而，方案的持续时间可以根据研究的确切目的而有所不同。
其他参数，例如刺激导管的?…
Declarações
The authors have nothing to disclose.
Acknowledgements
这项工作得到了罗马尼亚教育和研究部CNCS – UEFISCDI的赠款支持，项目编号PN-III-P1-1.1-TE-2019-0370，在PNCDI III内。
Materials
| Antisedan (Atipamezole Hydrochloride) 5mg / mL, solution for injection | Orion Corporation | 06043/4004 | for Rats use 1 mg / kg |
| Dormitor (Medetomidine Hydrochloride) 1 mg / mL, solution for injection | Orion Corporation | 06043/4003 | for Rats use 0.5 mg / kg |
| E-Z Anesthesia Single Animal System | E-Z Systems Inc | EZ-SA800 | Allows the manipulation of one animal at a time |
| Isoflurane 99.9%, 100 mL | Rompharm Company | N01AB06 | |
| Ketamine 10%, 25 mL | for Rats use 75 mg / kg | ||
| Microcontroller-based cardiac pacemaker for small animals | Developed in our laboratory (See Reference number 10 in the manuscript) | ||
| Surface ECG recording system | Developed in our laboratory (See Reference number 10 in the manuscript) |
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