Choi Eue-Keun, Shen Mark J, Lin Shien-Fong, Chen Peng-Sheng, Oh Seil
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea.
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Europace. 2014 Jul;16(7):1083-91. doi: 10.1093/europace/eut364. Epub 2014 Jan 26.
We hypothesized that carvedilol can effectively suppress autonomic nerve activity (ANA) in ambulatory dogs during sinus rhythm and atrial fibrillation (AF), and that carvedilol withdrawal can lead to rebound elevation of ANA. Carvedilol is known to block pre-junctional β2-adrenoceptor responsible for norepinephrine release.
We implanted radiotransmitters to record stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and superior left ganglionated plexi nerve activity (SLGPNA) in 12 ambulatory dogs. Carvedilol (12.5 mg orally twice a day) was given for 7 days during sinus rhythm (n = 8). Four of the eight dogs and an additional four dogs were paced into persistent AF. Carvedilol reduced heart rate [from 103 b.p.m. (95% confidence interval (CI), 100-105) to 100 b.p.m. (95% CI, 98-102), P = 0.044], suppressed integrated nerve activities (Int-NAs, SGNA by 17%, VNA by 19%, and SLGPNA by 12%; all P < 0.05 vs. the baseline), and significantly reduced the incidence (from 8 ± 6 to 3 ± 3 episodes/day, P < 0.05) and total duration (from 68 ± 64 to 16 ± 21 s/day, P < 0.05) of paroxysmal atrial tachycardia (PAT). Following the development of persistent AF, carvedilol loading was associated with AF termination in three dogs. In the remaining five dogs, Int-NAs were not significantly suppressed by carvedilol, but SGNA significantly increased by 16% after carvedilol withdrawal (P < 0.001).
Carvedilol suppresses ANA and PAT in ambulatory dogs during sinus rhythm.
我们假设卡维地洛能有效抑制动态心电图监测的犬在窦性心律和心房颤动（AF）期间的自主神经活动（ANA），且停用卡维地洛会导致ANA反弹性升高。已知卡维地洛可阻断负责去甲肾上腺素释放的节前β2 - 肾上腺素能受体。
我们在12只动态心电图监测的犬中植入无线电发射器，以记录星状神经节神经活动（SGNA）、迷走神经活动（VNA）和左上神经节丛神经活动（SLGPNA）。在窦性心律期间（n = 8），给予卡维地洛（12.5 mg口服，每日两次），持续7天。8只犬中的4只以及另外4只犬被起搏诱发持续性AF。卡维地洛降低了心率[从103次/分钟（95%置信区间（CI），100 - 105）降至100次/分钟（95% CI，98 - 102），P = 0.044]，抑制了综合神经活动（Int - NAs，SGNA降低17%，VNA降低19%，SLGPNA降低12%；与基线相比，所有P < 0.05），并显著降低了阵发性房性心动过速（PAT）的发生率（从8 ± 6次/天降至3 ± 3次/天，P < 0.05）和总持续时间（从68 ± 64秒/天降至16 ± 21秒/天，P < 0.05）。在持续性AF发生后，卡维地洛负荷剂量给药使3只犬的AF终止。在其余5只犬中，卡维地洛未显著抑制Int - NAs，但停用卡维地洛后SGNA显著增加了16%（P < 0.001）。
卡维地洛在窦性心律期间抑制动态心电图监测的犬的ANA和PAT。
