Prolongation of QT Interval by Terbutaline in Healthy Subjects

In a double-blind, randomized placebo-controlled crossover study, we characterized how terbutaline prolonged cardiac corrected QT interval (QTc). The study was carried out in six young and healthy male subjects in supine position. Escalating terbutaline doses were administered intravenously at infusion rates of 6 mL/h (10 microg terbutaline/min), 12 mL/h (20 microg terbutaline/min), and 18 mL/h (30 microg terbutaline/min). Terbutaline maximally prolonged QTc intervals on average by 60%, from 358 milliseconds (SD 28) to 456 milliseconds (SD 19). The effect was closely associated with a simultaneous decrease in plasma potassium concentration from 4.0 mmol/L (SD 0.1) to 2.5 mmol/L (SD 0.1). The final phase of slow ventricular repolarization, the interval between the apex and the end of T wave, was proven to be highly sensitive to the hypokalemic terbutaline actions, whereas the earlier repolarization phases were not strongly affected by terbutaline. Estimated by using the classic Nernst equation for membrane potentials, terbutaline-induced hypokalemia hyperpolarized ventricular myocardium from the resting level of -90 mV to -110 mV. The prolongation of QTc interval was related to ventricular hyperpolarization with a Pearson correlation coefficient of 0.91. Terbutaline-induced prolongation of QTc interval in healthy volunteers is in conformity with repolarization studies carried out in isolated canine heart ventricular preparations in which the cardiac ventricular cell membrane potential determines the duration of the final phase of slow ventricular repolarization.