Laurent Gabriel, Moe Gordon, Hu Xudong, Leong-Poi Howard, Connelly Kim A, So Petsy Pui-Sze, Ramadeen Andrew, Doumanovskaia Liia, Konig Andrea, Trogadis Judy, Courtman David, Strauss Bradley, Dorian Paul
Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1206-15. doi: 10.1152/ajpheart.00999.2007. Epub 2008 Jan 4.
Rapid ventricular pacing (RVP) is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. We performed acute, short-term, simultaneous atrioventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 s. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure, and a significantly greater decrease in left atrial emptying function (-84.4 +/- 38.6% vs. -23.7 +/- 27.1%, P < 0.05) than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight dogs in the control group (no pacing), eight dogs in the RVP group (2 wk at 240 beats/min followed by 3 wk at 220 beats/min), and fourteen dogs in the SAVP group (2 wk at 220 beats/min). SAVP induced less left ventricular dysfunction but more left atrial dysfunction than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, P < 0.05) and maintenance (median 1,660 vs. 710 s, P < 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared with RVP dogs (6.9 +/- 1.5 vs. 4.8 +/- 1.6, respectively, P < 0.05 vs. 1.1 +/- 0.7 in unpaced control dogs). In conclusion, the SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions.
快速心室起搏（RVP）是一种公认的心房颤动（AF）动物模型。然而，该模型存在死亡率高和严重心力衰竭的局限性。我们研究的目的是评估一种新的可诱导AF的犬模型。我们对14只犬进行了急性、短期、同时房室起搏（SAVP）和RVP（顺序随机），持续30秒。与RVP相比，SAVP产生了更多的超声心动图肺静脉血流逆转、平均肺毛细血管楔压更大的升高以及左心房排空功能显著更大的降低（-84.4±38.6%对-23.7±27.1%，P<0.05）。30只犬被随机分为三个长期研究组：对照组8只犬（无起搏），RVP组8只犬（2周240次/分钟，随后3周220次/分钟），SAVP组14只犬（2周220次/分钟）。与RVP相比，SAVP诱导的左心室功能障碍较少，但左心房功能障碍较多。SAVP犬与RVP犬的心房有效不应期相似，但与RVP犬相比，传导的异质性更大，AF的诱导率更高（83%对40%，P<0.05），维持率更高（中位数1660对710秒，P<0.05）。与RVP犬相比，SAVP诱导更多的胶原周转，并且与心房中III型胶原的显著更大增加相关（分别为6.9±1.5对4.8±1.6，与未起搏对照组犬的1.1±0.7相比，P<0.05）。总之，SAVP模型诱导了深刻的机械和基质心房重塑以及可重复的持续性AF。这种新模型具有临床相关性，可能有助于测试AF干预措施。
