Sympathomimetic Infusion and Cardiac Repolarization: The Normative Effects of Epinephrine and Isoproterenol in Healthy Subjects

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Abstract
Catecholamines are known to affect cardiac repolarization, and provocation with either isoproterenol or epinephrine has been proposed as a tool for uncovering latent repolarization abnormalities. This study systematically compares the effects of isoproterenol and epinephrine infusions on QT interval (QT), T waves and U waves in normal subjects. Twenty-four normal subjects (29 +/- 8 years) were evaluated during graded infusions of up to 0.30 microg/kg/minute epinephrine and 5.0 microg/minute isoproterenol. Heart rates at peak doses were 81 +/- 13 bpm at 0.28 +/- 0.04 microg/kg/minute epinephrine and 104 +/- 5 bpm at 2.4 microg/minute isoproterenol. The longest absolute QT increase was 4 +/- 5 msec above baseline during isoproterenol (P < 0.001) and 12 +/- 23 msec during epinephrine (P = 0.07), while the longest corrected QT interval (QTc) increase was 67 +/- 28 msec (P < 0.0001) and 79 +/- 40 msec (P < 0.0001) above baseline during isoproterenol and epinephrine, respectively (P = 0.12 for difference). There was a 2-fold increase in U-wave amplitude during each intervention (P < 0.001). The specificity of paradoxical QT prolongation (>or=30 msec at 0.05 microg/kg/minute or >or=35 msec at 0.10 microg/kg/minute epinephrine) and an increase in QTc >or=600 msec at any dose epinephrine were 100%. However, the specificity of other proposed criteria that utilized QTc measurement (>or=30 msec at 0.10 microg/kg/minute or >or=65 msec at any dose) was poor whether all leads or only lead II were assessed. Both epinephrine and isoproterenol are associated with QTc prolongation and amplification of the U wave in normal subjects. The specificity of proposed criteria for epinephrine provocation in diagnosis of the long-QT syndrome is variable; however, paradoxical QT prolongation at low-dose epinephrine or a QTc >or=600 msec is highly specific.