To evaluate whether heart-rate-induced changes of the QT interval are dependent on autonomic tone, we studied 13 healthy subjects, mean age 67.5 years. The maximal uncorrected QT from leads I, II, V1 and V" was determined during atrial pacing at 90 beats/min and 130 beats/min before and after i.v. administration of propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg. Significant reductions (p < 0.01) of QT were induced by the paced increases in heart rate before drugs (10%), after propranolol

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... and after the combination of atropine and propranolol (9%). Propranolol caused no significant change in the QT interval when heart rate was held constant by pacing. In contrast, atropine produced rate-independent reductions of QT interval (5%) in subjects with ,3-adrenergic blockade (p < 0.05). Bazett's formula for heart-rate correction of the QT interval (QTc) was not applicable for atrial overdrive pacing, as it gave proportionately longer QTc values at higher heart rates. These results show that heart rate is a major determinant of the duration of the QT interval and that paced changes in heart rate induce QT-interval responses that are essentially uninfluenced by autonomic tone. The rate-independent effect of the QT interval produced by elimination of cholinergic tone suggests a direct influence of cholinergic activity on the repolarization of ventricular myocardium.