Norepinephrine induces action potential prolongation and early afterdepolarizations in ventricular myocytes isolated from human end-stage failing hearts

Aims Congestive heart failure is characterized by high levels of norepineph rine which is considered to be arrhythmogenic. It is unclear whether increa sed norepinephrine is only a marker of the severity of heart failure or whe ther it directly triggers ventricular arrhythmias. Methods and Results Ventricular myocytes were isolated from eight explanted hearts of patients with end-stage heart failure (ischaemic or dilated card iomyopathy). With the whole-cell configuration of the patch-clamp technique the effect of 1 mu mol.l(-1) norepinephrine on action potentials and membr ane currents was studied. The cells had a membrane capacitance of 256 +/- 2 5 pF (n=26) and action potential duration (APD90) during control conditions was 620 +/- 45 ms at 1 Hz (n=14). Norepinephrine induced action potential prolongation in all cells and early afterdepolarizations in 50% of them. No repinephrine significantly increased the calcium current but had no effect on the delayed rectifier current, the inward rectifier current or the trans ient outward current. Norepinephrine also significantly increased the stead y-state calcium window-current measured between -40 and 0 mV. Conclusions In contrast to many animal species, norepinephrine induces acti on potential prolongation in ventricular myocytes from human failing hearts ; as well as early afterdepolarization, by an increase in both the calcium peak current and window current. Thus norepinephrine seems to be an importa nt arrhythmogenic factor in congestive heart failure. (C) 2001 The European Society of Cardiology.