Garratt C J, Duytschaever M, Killian M, Dorland R, Mast F, Allessie M A
Department of Physiology, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
J Cardiovasc Electrophysiol. 1999 Aug;10(8):1101-8. doi: 10.1111/j.1540-8167.1999.tb00283.x.
Episodes of atrial fibrillation (AF) are known to cause both a rapid reduction in atrial refractoriness (atrial electrical remodeling) and a more delayed increase in AF stability in the chronic goat model. The aims of this study were to examine (1) the hypothesis that an AF-induced increase in AF stability might be due to a mechanism with a longer onset and offset than that of changes in refractoriness and (2) the possibility that repeated paroxysms of maintained AF might cause a cumulative increase in AF stability independent of changes in atrial refractoriness.
AF was maintained by rapid atrial pacing in seven goats for three consecutive 5-day periods, each separated from each other by 48 hours of sinus rhythm. Assessments of atrial refractory periods, conduction velocity, AF inducibility, and duration of individual episodes of AF were attempted at intervals throughout the protocol. Forty-eight hours of sinus rhythm was just sufficient for refractoriness changes to fully reverse in all goats, with no evidence of any "residual" increase in AF inducibility. There was no significant difference among any of the three periods of pacing-maintained AF with regard to time to develop episodes of AF of 60-second duration (22.1+/-13, 23.8+/-16, and 30.3+/-29 hours), 1-hour duration (56.6+/-28, 61.3+/-31, and 60.1+/-32 hours), or 24-hour duration (84.0+/-31, 87.0+/-33, and 83.5+/-32 hours).
There is no evidence for a cumulative effect of AF paroxysms on AF inducibility or stability independent of changes in refractoriness. These findings highlight the importance of atrial refractoriness as a potential target for antiarrhythmic strategies aimed at inhibiting the self-perpetuation of AF.
在慢性山羊模型中,已知房颤(AF)发作会导致心房不应期迅速缩短(心房电重构)以及房颤稳定性出现更延迟的增加。本研究的目的是检验:(1)房颤诱导的房颤稳定性增加可能是由于一种起效和消退时间比不应期变化更长的机制这一假设;(2)持续性房颤的反复阵发性发作可能导致房颤稳定性累积增加而与心房不应期变化无关的可能性。
通过快速心房起搏使7只山羊维持房颤状态,连续3个5天周期,每个周期之间间隔48小时的窦性心律。在整个实验过程中,定期尝试评估心房不应期、传导速度、房颤诱发性以及单个房颤发作的持续时间。48小时的窦性心律刚好足以使所有山羊的不应期变化完全逆转,没有证据表明房颤诱发性有任何“残留”增加。在起搏维持房颤的三个时期中,对于60秒持续时间的房颤发作时间(22.1±13、23.8±16和30.3±29小时)、1小时持续时间(56.6±28、61.3±31和60.1±32小时)或24小时持续时间(84.0±31、87.0±33和83.5±32小时),均无显著差异。
没有证据表明房颤阵发性发作对房颤诱发性或稳定性有独立于不应期变化的累积效应。这些发现凸显了心房不应期作为旨在抑制房颤自我持续的抗心律失常策略潜在靶点的重要性。