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. 2001 Jul;86(1):45–51. doi: 10.1136/heart.86.1.45

β2 Adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium

M Lowe 1, E Rowland 1, M Brown 1, A Grace 1
PMCID: PMC1729813  PMID: 11410561

Abstract

OBJECTIVE—To define the effects of β2 adrenergic receptor stimulation on ventricular repolarisation in vivo.
DESIGN—Prospective study.
SETTING—Tertiary referral centre.
PATIENTS—85 patients with coronary artery disease and 22 normal controls.
INTERVENTIONS—Intravenous and intracoronary salbutamol (a β2 adrenergic receptor selective agonist; 10-30 µg/min and 1-10 µg/min), and intravenous isoprenaline (a mixed β1/β2 adrenergic receptor agonist; 1-5 µg/min), infused during fixed atrial pacing.
MAIN OUTCOME MEASURES—QT intervals, QT dispersion, monophasic action potential duration.
RESULTS—In patients with coronary artery disease, salbutamol decreased QTonset and QTpeak but increased QTend duration; QTonset-QTpeak and QTpeak-QTend 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 QTonset, QTpeak, and QTend which was more pronounced in patients with coronary artery disease—for example, QTend 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—β2 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.


Keywords: β2 adrenergic receptors; ventricular repolarisation; QT dispersion; salbutamol; isoprenaline

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Figure 1  .

Figure 1  

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Experimental protocols for infusion schedules, ECG, and monophasic action potential (mAP) data collection. See text for details. HR, heart rate; ISDN, isosorbide dinitrate.

Figure 2  .

Figure 2  

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Blood pressure responses following (A) intravenous salbutamol (0-30 µg/min) and (B) intravenous isoprenaline (0-5 µg/min). Systolic, diastolic, and mean blood pressure responses are shown.

Figure 3  .

Figure 3  

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Typical ECG recordings obtained during fixed atrial pacing at baseline (left) and with intravenous salbutamol (30 µg/min) (right). QTend interval for each ECG complex indicated by broken lines.

Figure 4  .

Figure 4  

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Changes in mean QTend, QTpeak, and QTonset during salbutamol infusion (0-30 µg/min) (left panel) and isoprenaline infusion (0-5 µg/min) (right panel). Responses have been separated for patients with coronary artery disease (CAD) and controls, and those taking (broken lines) and not taking (unbroken lines) atenolol. There is a dose dependent decrease in QTonset and QTpeak, but an increase in QTend in coronary artery disease patients.

Figure 5  .

Figure 5  

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Changes in QTend dispersion following (A) intravenous salbutamol and (B) intravenous isoprenaline. There are large increases in QT dispersion following both salbutamol and isoprenaline in coronary artery disease and control patients.

Figure 6  .

Figure 6  

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Changes in QTend dispersion (QTd) and serum potassium (K+) during initial high dose intravenous infusion of salbutamol. There is a pronounced increase in QTd before any significant decrease in serum potassium.

Figure 7  .

Figure 7  

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QTend dispersion following (A) intravenous hydralazine (0-300 µg/min) and (B) intravenous isosorbide dinitrate (ISDN) (0-600 µg/min). There were no significant changes seen during infusion with either agent.

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