Keefe Joshua A, Navarro-Garcia Jose Alberto, Ni Li, Reilly Svetlana, Dobrev Dobromir, Wehrens Xander H T
Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA.
J Cardiovasc Aging. 2022;2. doi: 10.20517/jca.2022.21. Epub 2022 Jul 19.
Postoperative atrial fibrillation (POAF), characterized as AF that arises 1-3 days after surgery, occurs after 30%-40% of cardiac and 10%-20% of non-cardiac surgeries, and is thought to arise due to transient surgery-induced triggers acting on a preexisting vulnerable atrial substrate often associated with inflammation and autonomic nervous system dysfunction. Current experimental studies often rely on human atrial tissue samples, collected during surgery prior to arrhythmia development, or animal models such as sterile pericarditis and atriotomy, which have not been robustly characterized.
To characterize the demographic, electrophysiologic, and inflammatory properties of a POAF mouse model.
A total of 131 wild-type C57BL/6J mice were included in this study. A total of 86 (65.6%) mice underwent cardiothoracic surgery (THOR), which consisted of bi-atrial pericardiectomy with 20 s of aortic cross-clamping; 45 (34.3%) mice underwent a sham procedure consisting of dissection down to but not into the thoracic cavity. Intracardiac pacing, performed 72 h after surgery, was used to assess AF inducibility. THOR mice showed greater AF inducibility (38.4%) compared to Sham mice (17.8%, = 0.027). Stratifying the cohort by tertiles of age showed that the greatest risk of POAF after THOR compared to Sham occurred in the 12-19-week age group. Stratifying by sex showed that cardiothoracic (CT) surgery increased POAF risk in females but had no significant effect in males. Quantitative polymerase chain reaction of atrial samples revealed upregulation of transforming growth factor beta 1 and interleukin 6 (IL6) and 18 (IL18) expression in THOR compared to Sham mice.
Here, we demonstrate that the increased POAF risk associated with CT surgery is most pronounced in female and 12-19-week-old mice, and that the expression of inflammatory cytokines is upregulated in the atria of THOR mice prone to inducible AF.
术后房颤（POAF）表现为术后1 - 3天出现的房颤，在30% - 40%的心脏手术和10% - 20%的非心脏手术后发生，被认为是由于手术诱发的短暂触发因素作用于预先存在的易损心房基质，该基质常与炎症和自主神经系统功能障碍相关。当前的实验研究通常依赖于在心律失常发生前手术期间采集的人类心房组织样本，或诸如无菌性心包炎和心房切开术等动物模型，而这些模型尚未得到充分的表征。
表征一种POAF小鼠模型的人口统计学、电生理和炎症特性。
本研究共纳入131只野生型C57BL/6J小鼠。共有86只（65.6%）小鼠接受了心胸手术（THOR），包括双心房心包切除术并伴有20秒的主动脉交叉钳夹；45只（34.3%）小鼠接受了假手术，即仅解剖至胸腔但不进入胸腔。术后72小时进行心内起搏，用于评估房颤的诱发能力。与假手术组小鼠（17.8%，P = 0.027）相比，THOR组小鼠显示出更高的房颤诱发率（38.4%）。按年龄三分位数对队列进行分层显示，与假手术组相比，THOR组术后发生POAF的最大风险出现在12 - 19周龄组。按性别分层显示，心胸（CT）手术增加了雌性小鼠发生POAF的风险，但对雄性小鼠无显著影响。与假手术组小鼠相比，心房样本的定量聚合酶链反应显示THOR组小鼠中转化生长因子β1以及白细胞介素6（IL6）和18（IL18）的表达上调。
在此，我们证明与CT手术相关的POAF风险增加在雌性和12 - 19周龄小鼠中最为明显，并且在易于诱发房颤的THOR组小鼠心房中炎症细胞因子的表达上调。
