Acetylcholine-Atropine Interactions: Paradoxical Effects on Atrial Fibrillation Inducibility.
Atropine (ATr) is well known as a cholinergic antagonist, however, at low concentrations ATr could paradoxically accentuate the parasympathetic actions of acetylcholine (ACh). In 22 pentobarbital anesthetized dogs, via a left and right thoracotomy, a leak-proof barrier was attached to isolate the atrial appendages (AAs) from the rest of the atria. In group 1 (Ach+ATr+Ach), ACh, 100 mM, was placed on the AA followed by the application of ATr, 2 mg/mL. The average atrial fibrillation (AF) duration was 17 ± 7 minutes. After ATr was applied to the AA and ACh again tested, the AF duration was markedly attenuated (2 ± 2 minutes, P < 0.05). In group 2 (ATr+Ach), ATr was initially applied to the AA followed by the application of ACh, 100 mM. There was no significant difference in AF duration (16 ± 4 minutes vs. 18 ± 2 minutes, P = NS). The inhibitory effect of ATr on induced HR reduction (electrical stimulation of the anterior right ganglionated plexi and vagal nerves) was similar between groups 1 and 2. These observations suggest that when ATr is initially administered it attaches to the allosteric site of the muscarinic ACh receptor (M2) leaving the orthosteric site free to be occupied by ACh. The M3 receptor that controls HR slowing does not show the same allosteric properties.
*Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; †Department of Medicine, Heart Rhythm Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, OK; and ‡Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yu
Y
Liu
Benjamin J
BJ
Scherlag
Youqi
Y
Fan
Wenfang
W
Xia
He
H
Huang
Sunny S
SS
Po
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000494:pharmacology*; D020517:Atrial Appendage / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D001285:Atropine / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002304:Cardiac Pacing, Artificial; D018679:Cholinergic Agonists / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D001285:Atropine; D000109:Acetylcholine