Sympathoexcitation Increases the QT/RR Slope in Healthy Men: Differential Effects of Hypoxia, Dobutamine, and Phenylephrine

INTRODUCTION: Dynamic ventricular repolarization assessed by QT/RR slopes studies the effects of modifications in cardiac repolarization independently of variations in RR interval (RR). The effects of changes in sympathetic and vagal activity on the QT/RR slope are controversial. We tested the hypothesis that sympathoexcitation is an important determinant of the QT/RR slope. METHODS AND RESULTS: We compared the effects of a reflex sympathetic activation in response to hypoxia, to the direct effects of the infusion of the beta-adrenergic agent dobutamine, on the QTa (apex) and QTe (end)/RR slopes. Dobutamine was titrated to obtain similar increases in cardiac output than with hypoxia. Cardiac vagal activity was estimated by rMSSD and pNN50. In a second group of healthy subjects, we assessed the effect of a reflex cardiac vagal activation in response to phenylephrine infusion on the same variables. We observed a similar increase in QTa and QTe slopes during hypoxia and dobutamine (both P < 0.017 vs. normoxia), despite divergent changes in cardiac vagal activity, as rMSSD and pNN50 decreased with hypoxia compared to normoxia (P < 0.001) but increased during dobutamine infusion compared to hypoxia (P < 0.017). In contrast, these slopes did not change during the rises in rMSSD and pNN50 elicited by phenylephrine (P > 0.7). CONCLUSION: Beta-adrenergic stimulation induces comparable increases in the QT/RR slopes than hypoxia, but in the presence of a larger cardiac vagal activity. Vagal cardiac activation by phenylephrine does not change the QT slopes. This reveals that the sympathetic system is an important determinant of QT/RR dynamicity in healthy men.