Sympathetic activation enhances QT prolongation by quinidine

Salt Restriction and QT Prolongation. Introduction: Salt restriction result s in endogenous sympathetic activation, and we previously showed that plasm a concentrations of quinidine measured after oral drug administration are i ncreased during a low-salt diet. However, it is not known whether, independ ent of effects on plasma concentration, the extent to which quinidine prolo ngs the QT interval also is modulated by changes in endogenous sympathetic activity. Methods and Results: In these studies, we evaluated quinidine concentration -QT relations during low-salt (10 mEq/day for 8 days) and high-salt (400 mE q/day for 8 days) diets, with or without beta blockade in normal volunteers . In the absence of beta blockade, the concentration producing a fixed (15% ) increase in QTc was significantly lower with salt restriction: 1.2 +/- 0. 4 mug/mL (low salt) versus 2.2 +/- 0.4 mug/mL (high salt) (P < 0.01). With beta blockade, this difference was abolished: 1.9 +/- 0.3 <mu>g/mL (low sal t + beta blockade) versus 2.1 +/- 0.3 mug/mL (high salt + beta blockade). Q T morphologic abnormalities including bifid T waves and U waves were abolis hed with beta-adrenergic blockade. Conclusion: Sympathetic activation by a low-salt diet not only modulates dr ug disposition but also increases sensitivity to drug-induced QT prolongati on.