Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium.
OBJECTIVE
To define the effects of beta(2) adrenergic receptor stimulation on ventricular repolarisation in vivo.


METHODS
Prospective study.


METHODS
Tertiary referral centre.


METHODS
85 patients with coronary artery disease and 22 normal controls.


METHODS
Intravenous and intracoronary salbutamol (a beta(2) adrenergic receptor selective agonist; 10-30 microg/min and 1-10 microg/min), and intravenous isoprenaline (a mixed beta(1)/beta(2) adrenergic receptor agonist; 1-5 microg/min), infused during fixed atrial pacing.


METHODS
QT intervals, QT dispersion, monophasic action potential duration.


RESULTS
In patients with coronary artery disease, salbutamol decreased QT(onset) and QT(peak) but increased QT(end) duration; QT(onset)-QT(peak) and QT(peak)-QT(end) intervals increased, resulting in T wave prolongation (mean (SEM): 201 (2) ms to 233 (2) ms; p < 0.01). There was a large increase in dispersion of QT(onset), QT(peak), and QT(end) which was more pronounced in patients with coronary artery disease-for example, QT(end) dispersion: 50 (2) ms baseline v 98 (4) ms salbutamol (controls), and 70 (1) ms baseline v 108 (3) ms salbutamol (coronary artery disease); p < 0.001. Similar responses were obtained with isoprenaline. Monophasic action potential duration at 90% repolarisation shortened during intracoronary infusion of salbutamol, from 278 (4.1) ms to 257 (3.8) ms (p < 0.05).


CONCLUSIONS
beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium. The increase in dispersion of repolarisation provides a mechanism whereby catecholamines acting through this receptor subtype may trigger ventricular arrhythmias.
Lowe
M D
MD
Department of Cardiology, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, UK.
Rowland
E
E
Brown
M J
MJ
Grace
A A
AA
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000704:Analysis of Variance; D016022:Case-Control Studies; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D000420:Albuterol