Effects of carvedilol on cardiac autonomic nerve activities during sinus rhythm and atrial fibrillation in ambulatory dogs.
OBJECTIVE
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.


RESULTS
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).


CONCLUSIONS
Carvedilol suppresses ANA and PAT in ambulatory dogs during sinus rhythm.
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.
Eue-Keun
EK
Choi
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Mark J
MJ
Shen
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Shien-Fong
SF
Lin
Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Peng-Sheng
PS
Chen
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 seil@snu.ac.kr.
Seil
S
Oh
D000284:Administration, Oral; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004285:Dogs; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D013617:Tachycardia, Supraventricular / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
D058669:Adrenergic alpha-2 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
Arrhythmia; Atrial fibrillation; Atrium; Autonomic nervous system; Carvedilol