Document Detail

Investigation of the effects of physiological and vasodilation-induced autonomic activation on the QTc Interval in healthy male subjects.
MedLine Citation:
PMID:  15963089     Owner:  NLM     Status:  MEDLINE    
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 beta-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 (Delta = 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.
E Berger; K Patel; S Anwar; W Davies; D J Sheridan
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  60     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-20     Completed Date:  2005-09-29     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  17-23     Citation Subset:  IM    
Academic Cardiology Unit, Division NHLI, Imperial College, St Mary's Hospital, London W2 1NY, UK.
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MeSH Terms
Cross-Over Studies
Exercise / physiology*
Heart Rate / drug effects,  physiology*
Mental Processes / physiology*
Nitroglycerin / pharmacology
Posture / physiology*
Vasodilation / physiology*
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Vasodilator Agents; 55-63-0/Nitroglycerin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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