5-Hydroxytryptamine causes rate-dependent arrhythmias through 5-HT4 receptors in human atrium: facilitation by chronic beta-adrenoceptor blockade.
We have investigated the ability of 5-hydroxytryptamine (5-HT) to elicit arrhythmic contractions in isolated human atrial strips as a function of pacing rate (0.1-2 Hz) using a method recently introduced by us (Kaumann and Sanders, this journal, 1993 b) and examined the nature of the 5-HT receptors involved. Right atrial appendage tissue was obtained from 14 patients undergoing cardiac surgery. None of the patients had advanced heart failure. 5-HT (0.6-20 mumol/l) induced arrhythmic contractions during pacing in 4/11 atrial strips from 3/4 patients who had not received beta blockers and in 21/27 atrial strips from 9/10 patients who had been chronically treated with beta blockers (primarily beta 1-selective). The incidence of arrhythmic contractions evoked by 5-HT did not reach statistical significance in the atrial tissue from the non-beta blocked patients but was highly significant in the atrial tissue from the chronically beta blocked patients. The arrhythmic contractions usually occurred more frequently at low than at high pacing rates and were observed at the physiological frequency of 1 Hz in 1/4 atrial strips from 1/4 of the non-beta blocked patients and 6/11 strips from 5/10 of the beta blocked patients. The 5-HT-evoked arrhythmic contractions were observed during blockade of beta 1-adrenoceptors, beta 2-adrenoceptors and 5-HT3 receptors, ruling out the participation of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Kaumann
A J
AJ
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK.
Sanders
L
L
D000317:Adrenergic alpha-Antagonists / Q000633:toxicity*; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D004357:Drug Synergism; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000633:toxicity*; D012702:Serotonin Antagonists / Q000494:pharmacology
C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin