title: Effect of phenylephrine with and without atropine on QT dispersion in healthy normotensive men.
abstract: The present study examined if changes in cardiac after-load would affect QT interval dispersion. QT dispersion (QTd) on the 12-lead electrocardiogram is believed to be a noninvasive measure of electrical inhomogeneity in the heart and has recently been identified as a sensitive predictor of sudden cardiac death. In experimental models, an increase in cardiac afterload has been shown to alter action potential durations through mechanoelectrical feedback. This may result in an altered dispersion of action potential repolarization in the ventricle. Until now, there has been little evidence for this occurring in man in vivo. In the present study, the effects of afterload on QTd were examined in 10 healthy male volunteers (mean age [SD] 25 years [4.5]) who received an intravenous infusion of phenylephrine (0.2 to 3.6 microg/kg/min) given in incremental doses, and placebo in a blinded, crossover fashion. Because phenylephrine is known to alter heart rate (HR) significantly (via a reflex vagal response), the study was performed with and without atropine. We found a significant positive correlation between acute changes in blood pressure (BP) and changes in all QTd indexes (deltaQTd/delta systolic BP and deltaQTcd/deltasystolic BP r values 0.67 and 0.60, respectively; p <0.001). This relation was independent of HR changes or reflex vagal activity. Atropine had no significant effect on QTd. These observations have important clinical implications and may partly account for why sudden deaths and arrhythmic complications occur so frequently in conditions associated with increased after-load, such as hypertension and heart failure.
authors.affiliation: University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom.
authors.forename: K M
authors.initials: KM
authors.lastname: Yee
authors.forename: P O
authors.initials: PO
authors.lastname: Lim
authors.forename: S A
authors.initials: SA
authors.lastname: Ogston
authors.forename: A D
authors.initials: AD
authors.lastname: Struthers
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001285:Atropine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D016757:Death, Sudden, Cardiac / Q000209:etiology; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D010656:Phenylephrine; D001285:Atropine