| Summary: | 博士 === 國立陽明大學 === 臨床醫學研究所 === 102 === Background: The autonomic nervous system has been found to play a critical role in the pathophysiology of atrial fibrillation (AF). Sympathetic tone influenced the occurrence of AF through an increase in the automaticity and triggered activity. Scherlag and colleagues had found that electrical stimulation of the autonomic ganglia at the atrium-pulmonary vein (PV) junction can transform the PV focal electrical activity into AF. In addition, increased vagal tone is frequently involved in the onset of the AF in patients with structurally normal heart. It is known that the autonomic innervation of the heart involves both the extrinsic and the intrinsic cardiac autonomic nervous system (ECANS, ICANS). The extrinsic system includes the ganglia in the brain and along the spinal cord with their axons (the so-called vagosympathetic trunk) en route to the heart; the intrinsic system contains the autonomic ganglia and axons located on the heart itself or along the great vessels in the thorax. The intrinsic cardiac autonomic system forms a complex neural network composed of ganglionated plexi (GP) concentrated within the epicardial fat pads and the interconnecting ganglia and axons. Stimulation of the intrinsic cardiac autonomic nervous system by applying high-frequency electrical activity to the GP or by injecting parasympathomimetics into the GP had drawn attention to the critical role of the intrinsic system in the dynamics of AF initiation and maintenance. it is important to keep the balanced intrinsic and extrinsic autonomic nervous systems. The interactions among each GPs and between extrinsic/intrinsic autonomic nervous system had not been well investigated before. In the acute animal study, we used the global mapping tool (EnSite Array) to identify the biatrial frequency distributions during AF and electrogram characteristics during sinus rhythm, and then investigate the chronic effect after interrupting the connection between ECANS and ICANS. Methods: In acute study, A mid sternal thoractomy was performed in anesthetized dogs. High frequency stimulation (20Hz, 0.1 ms duration) was applied to locate the GPs and achieve vagosympathetic stimulation (VNS). There were four major GPs, which were located near the 4 pulmonary vein (PV) ostia, and a third fat pad (SVC-Ao) GP which was located near the superior vena cava (SVC)-right atrial (RA) junction. To further study the chronic effect after interrupting the connection between ECANS and ICANS, dogs received ablation targeting the SVC-Ao GP. A second operation and the same measurements were made 10 weeks later. A pacemaker with lead implanted at right superior PV recorded AF or tachycardia (AT). Results: During AF, without VNS (n=12), the left atrial (LA) mean (8.20±0.11 vs. 7.95±0.30 Hz, p=0.04) and max (9.86±0.28 vs. 9.43±0.29 Hz, p=0.03) DFs were higher during the PV ostial GP stimulation than the SVC-Ao GP stimulation. The LA max DFs were located not only at the primary GPs but also the nearby secondary PV ostial GPs. The RA mean DF (8.36±0.05 vs. 7.99±0.19 Hz, p=0.04) was higher during SVC-Ao GP stimulation than PV ostial GP stimulation. The max DF was located inside the SVC during SVC-Ao GP stimulation and at the RA septum during PV ostial GP stimulation. With VNS (n=12), the LA mean and max DFs between the PV ostial and SVC-Ao GP stimulation were similar. The DF distribution shifted to non-GP LA sites during both the PV ostial and SVC-Ao GP stimulation. During sinus rhythm, The majority of AF nests were close to the GPs (52±18% of total AF nests). After GP ablation, the mean LA DF values decreased from 54±7Hz to 49±4Hz (p=0.023), DF values of AF nest decreased from 93±2Hz to 87±4Hz (p=0.001). In the chronic study, the dogs received interruption between ECANS and ICANS showing effective refractory periods decreased and AF/AT burden increased significantly from 4 and 5 weeks respectively after the first operation in the dogs receiving interruptions, compared to those without interruptions. Conclusions: The findings indicate that the AF was caused by an interaction between the PV ostial GPs during intrinsic autonomic stimulation, whereas the non-GP LA sites were responsible for the AF induced by an extrinsic neural input. The ICANS also increased the DF values during sinus rhythm, indicating that ICANS may play an important role in the mechanism of AF nest. Ablation of the “head station” GP between ECANS and ICANS prolonged the ERP acutely, but shortened regional ERPs and increased AF/AT burden chronically, suggesting that ECANS may tonically inhibit the ICANS activity.
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