Zhang Ling, Po Sunny S, Wang Huan, Scherlag Benjamin J, Li Hongliang, Sun Juan, Lu Yanmei, Ma Yitong, Hou Yuemei
*Cardiovascular Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China; †Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK; and ‡Department of Cardiovascular Diseases, The 6th People's Hospital, Shanghai Jiaotong University, Shanghai, China.
J Cardiovasc Pharmacol. 2015 Sep;66(3):307-15. doi: 10.1097/FJC.0000000000000281.
The mechanism(s) of how atrial fibrillation (AF) sustains itself in the first 24 hours is not well understood.
We sought to investigate the role of autonomic remodeling in the first 24 hours of AF simulated by rapid atrial pacing (RAP).
Forty-eight rabbits were divided into 6 groups. One group (n = 8) was euthanized after baseline recordings. Another group (n = 8) did not receive RAP during the 24-hour period to serve as controls. In the other 4 groups, rabbits were euthanized after RAP for 4, 8, 12, or 24 hours (n = 8 for each). Before and after designated hours of RAP, atrial effective refractory period, heart rate variability, and left vagal and sympathetic nerve activity (VNA and SNA, respectively) were determined. The right and left atrial tissues were obtained for immunocytochemical analysis for growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and choline acetyltransferase (ChAT).
RAP resulted in progressively shortened atrial effective refractory period and slower heart rate. In the first 12 hours of RAP, both SNA and VNA progressively increased. Then, VNA remained stably elevated but SNA began to attenuate. The high-frequency component and low-frequency/high-frequency ratio of heart rate variability followed the trend of VNA and SNA, respectively. The density of GAP43-positive, ChAT-positive, and TH-positive neural elements in the right and left atria was progressively higher with RAP.
AF resulted in progressive autonomic remodeling, manifesting as nerve sprouting, sympathetic and vagal hyperinnervation. Autonomic remodeling may play an important role in sustaining AF in the first 24 hours.
心房颤动(AF)在最初24小时内自我维持的机制尚未完全明确。
我们试图研究自主神经重塑在快速心房起搏(RAP)模拟的AF最初24小时内所起的作用。
48只兔子被分为6组。一组(n = 8)在进行基线记录后实施安乐死。另一组(n = 8)在24小时期间未接受RAP,作为对照组。在其他4组中,兔子在RAP 4、8、12或24小时后实施安乐死(每组n = 8)。在指定的RAP时间前后,测定心房有效不应期、心率变异性以及左迷走神经和交感神经活动(分别为VNA和SNA)。获取左右心房组织,进行生长相关蛋白43(GAP43)、酪氨酸羟化酶(TH)和胆碱乙酰转移酶(ChAT)的免疫细胞化学分析。
RAP导致心房有效不应期逐渐缩短,心率减慢。在RAP的最初12小时内,SNA和VNA均逐渐增加。然后,VNA保持稳定升高,但SNA开始减弱。心率变异性的高频成分和低频/高频比值分别遵循VNA和SNA的变化趋势。随着RAP进行,左右心房中GAP43阳性、ChAT阳性和TH阳性神经元的密度逐渐升高。
AF导致进行性自主神经重塑,表现为神经发芽、交感和迷走神经支配过度。自主神经重塑可能在AF最初24小时的维持中起重要作用。