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Investigation of the effects of physiological and vasodilation‐induced autonomic activation on the QTc Interval in healthy male subjects
Author(s) -
Berger E.,
Patel K.,
Anwar S.,
Davies W.,
Sheridan D. J.
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02371.x
Subject(s) - qt interval , atenolol , medicine , vasodilation , heart rate , cardiology , long qt syndrome , anesthesia , impedance cardiography , pharmacology , blood pressure , stroke volume
Aims Drug‐induced prolongation of the QTc interval is an important marker for potential proarrhythmic action. Prolongation of the QTc interval results from alteration of the ionic currents that regulate cardiac repolarisation. Such effects may result from direct drug action or alternatively they could also occur indirectly by drug‐induced modulation of autonomic tone, which is known to regulate cardiac repolarization. This study examined the effects of physiological and drug‐induced autonomic activation on heart rate, QT and QTc intervals. Methods We studied 29 healthy male subjects aged 18–30 years. Electrocardiographs were recorded before and during autonomic activation induced by mental activation, standing, exercise and glyceryl trinitrate (GTN) (0.5 mg sublingual)‐induced vasodilation in the presence and absence of β‐blockade (atenolol 100 mg daily for 4 days). QT intervals were measured manually by electronic callipers and corrected using the Fridericia formula. Results Heart rates were significantly increased during mental arithmetic, standing, exercise and GTN and this effect was significantly attenuated by atenolol, except for mental activation. QTc intervals were significantly reduced on standing and exercise and this was significantly attenuated by atenolol during exercise. In contrast, GTN increased QTc intervals (Δ = 5.7 ms, confidence interval ± 3.2 ms, P < 0.005) and this was not attenuated by atenolol. Conclusions Alteration in QTc intervals may result from physiological manoeuvres and vasodilation, interventions known to induce autonomic activation. We suggest that QTc prolongation due to GTN is indirectly mediated and unlikely to carry any proarrhythmic effect. Understanding whether drug‐induced QTc prolongation is directly or indirectly mediated may be important to determine any potential proarrhythmic risk.