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ORIGINAL RESEARCH ARTICLE

Refractoriness of the Sheep Superior Vena Cava Myocardial Sleeve

Cuimei Zhao^*,,1, Jie Qi^*,,1, Xingyuan Liu^,1, Huaizhi Chen^*,,1, Jun Li^*,, Yi Liu, Lei Liang^*,, Yangyang Zhang^*, Junjie Xiao^,, Li Li, Luying Peng, Jiahong Xu^*, Jun Ma^*, Ying Yang^*, Xianzheng Wu^* and Yi-Han Chen^*,,,2

^* Department of Cardiology, Tongji Hospital, Heart Rhythm Research Center, and Institute of Medical Genetics, Tongji University, Shanghai 200065, China

To whom requests for reprints should be addressed at ² Department of Cardiology, Tongji Hospital, Tongji University, 389 Xin Cun Road, Shanghai 200065, China. E-mail: yihanchen{at}mail.tongji.edu.cn

The cardiomyocytes in the superior vena cava (SVC) myocardial sleeve have distinct action potentials and ionic current profiles, but the refractoriness of these cells has not been reported. Using standard intracellular microelectrode techniques, we demonstrated in sheep that the effective refractory period (ERP) of the cardiomyocytes in the SVC (114.7 ± 6.5 ms) is shorter than that in the inferior vena cava (IVC) (166.7 ± 6.2 ms), right atrial free wall (RAFW) (201.0 ± 6.0 ms) and right atrial appendage (RAA) (203.1 ± 5.8 ms) (P < 0.05). The right atrial cardiomyocyte ERP was heterogeneously shortened by acetylcholine, a muscarinic type 2 receptor (M₂R) agonist. After perfusion with 15 µM acetylcholine, the shortest ERP occurred in the SVC (the ERP in the SVC, IVC, RAFW and RAA was 53.6 ± 2.7, 98.9 ± 2.2, 121.8 ± 6.0 and 109.7 ± 5.1 ms, respectively; P < 0.05). Carbachol (1 µM), another M₂R agonist, produced a similar effect as acetylcholine. Furthermore, we used methoctramine, a M₂R blocker, 4-DAMP, a muscarinic type 3 receptor (M₃R) blocker, and tropicamide, a muscarinic type 4 receptor (M₄R) blocker to inhibit the acetylcholine-induced ERP shortening of SVC cardiomyocytes, and found that the 50% inhibitory concentration for methoctramine, 4-DAMP and tropicamide was 5.91, 45.72 and 80.34 nM, respectively. Therefore, we conclude that the sheep SVC myocardial sleeve is a unique electrophysiological region of the right atrium with the shortest ERP both under physiological condition and under cholinergic agonist stimulation. M₂R might play a major role in the response of the SVC myocardial sleeve to parasympathetic nerve tone. The association between the distinct refractoriness in SVC and atrial fibrillation originating from the region deserves further investigation.

Key Words: superior vena cava • myocardial sleeve • refractoriness • acetylcholine • muscarinic type 2 receptor • atrial fibrillation