Ueda Norihiro, Yamamoto Mitsuru, Honjo Haruo, Kodama Itsuo, Kamiya Kaichiro
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Cardiovasc Res. 2014 Nov 1;104(2):364-70. doi: 10.1093/cvr/cvu202. Epub 2014 Sep 2.
The aim of this study was to investigate the role of gap junctions in atrial fibrillation (AF) by analysing the effects of a gap junction enhancer and blocker on AF vulnerability and electrophysiological properties of isolated hearts.
The acute atrial stretch model of AF in the isolated rabbit heart was used. Sustained AF (SAF) was induced by a burst of high-frequency stimulation of the Bachmann's bundle. The effective refractory period (ERP) was measured, and the total conduction time (TCT) and the pattern of conduction of the anterior surface of the left atrium were monitored by using an optical mapping system. The effect of enhancing gap junction function by 100-1000 nM rotigaptide (ZP123) and block by 30 μM carbenoxolone on these parameters was measured. SAF inducibility was increased with an elevation of intra-atrial pressure. Enhanced gap junction conductance induced by treatment with 100-1000 nM rotigaptide reduced SAF inducibility, and the gap junction blocker carbenoxolone increased SAF inducibility. In the absence of gap junction enhancer or blocker, normal conduction was observed at 0 cmH2O. When intra-atrial pressure was raised to 12 cmH2O, the conduction pattern was changed to a heterogeneous zig-zag pattern and TCT was prolonged. Conduction pattern was not affected by either agent. Rotigaptide shortened TCT, whereas carbenoxolone prolonged TCT. ERP was significantly shortened with an increase in intra-atrial pressure, but ERP was unaffected by either agent.
Gap junction modulators changed AF inducibility through their effects on atrial conduction, not by altering ERP.
本研究旨在通过分析缝隙连接增强剂和阻滞剂对房颤易感性及离体心脏电生理特性的影响，探讨缝隙连接在房颤（AF）中的作用。
采用离体兔心脏急性心房牵张房颤模型。通过对巴赫曼束进行高频刺激诱发持续性房颤（SAF）。测量有效不应期（ERP），并使用光学标测系统监测左心房前表面的总传导时间（TCT）和传导模式。测定100 - 1000 nM罗替戈汀（ZP123）增强缝隙连接功能及30 μM卡贝缩酮阻断缝隙连接对这些参数的影响。SAF诱导率随房内压升高而增加。100 - 1000 nM罗替戈汀处理诱导的缝隙连接电导增强降低了SAF诱导率，而缝隙连接阻滞剂卡贝缩酮增加了SAF诱导率。在没有缝隙连接增强剂或阻滞剂的情况下，在0 cmH2O时观察到正常传导。当房内压升至12 cmH2O时，传导模式变为异质性之字形模式且TCT延长。两种药物均未影响传导模式。罗替戈汀缩短了TCT，而卡贝缩酮延长了TCT。ERP随房内压升高显著缩短，但两种药物均未影响ERP。
缝隙连接调节剂通过影响心房传导而非改变ERP来改变房颤诱导率。
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