Sympathomimetic infusion and cardiac repolarization: the normative effects of epinephrine and isoproterenol in healthy subjects.

INTRODUCTION: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Effect of acute cocaine administration on the QTc interval of habitual users.

The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p <0.0001). One patient developed accelerated junctional rhythm, and 5 had nonspecific ST-T-wave abnormalities. The electrocardiograms revealed significant prolongation of the QTc interval (p <0.001) after cocaine administration. In addition, T-wave amplitude decreased and U-wave amplitude increased in response to cocaine use (p <0.05). QRS duration was unchanged by cocaine, whereas the PR interval shortened slightly. The repolarization changes observed after cocaine use were similar to those reported for other sympathomimetic agents and may be a contributing factor in the association between cocaine use and ventricular arrhythmias.