Both beta 1- and beta 2-adrenoceptors mediate catecholamine-evoked arrhythmias in isolated human right atrium.
The involvement of beta 1- and beta 2-adrenoceptors in catecholamine-evoked arrhythmias was investigated in isolated human right atrial appendages obtained from 22 patients chronically treated with beta blockers (usually beta 1-selective) and 9 patients not treated with beta blockers. A simple experimental model that assesses the incidence of arrhythmic contractions as a function of heart rate (pacing) is introduced. beta 1-adrenoceptors were activated by (-)-noradrenaline during beta 2-adrenoceptor blockade with 50 nmol/l ICI 118551. beta 2-adrenoceptors were activated by (-)-adrenaline during beta 1-adrenoceptor blockade with 300 nmol/l CGP 20712A. Both (-)-noradrenaline and (-)-adrenaline caused arrhythmic contractions whose incidence was greater at low than at high pacing rates. CGP 20712A (300 nmol/l) blocked the (-)-noradrenaline-evoked contractions in 1/1 atrial strip from 1/1 patient not treated with a beta blocker and 17/17 atrial strips from 15/15 patients chronically treated with beta blockers. ICI 118551 (50 nmol/l) blocked the (-)-adrenaline-evoked contractions in 3/4 atrial strips from 3/4 patients not treated with beta blockers and 17/20 atrial strips from 15/18 patients chronically treated with beta blockers. The incidence of arrhythmic contractions evoked by both (-)-noradrenaline and (-)-adrenaline was higher in chronically beta blocked patients than in non beta blocked patients. We conclude that both beta 1- and beta 2-adrenoceptors mediate atrial arrhythmias and that the generation of these arrhythmias is facilitated by chronic beta 1-adrenoceptor blockade.
Kaumann
A J
AJ
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK.
Sanders
L
L
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002395:Catecholamines / Q000633:toxicity*; D004558:Electric Stimulation; D004594:Electrophysiology; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D002395:Catecholamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2