Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts

Background-Heterogeneity of sympathetic innervation is thought to contribut e to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. Methods and Results-To assess this relationship, we measured activation rec overy intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 wee ks after regional denervation produced by phenol and 4 sham-operated rabbit s. ARI results were compared with the distribution of sympathetic innervati on measured from 3D reconstructions of serial autoradiographs of [I-125]met aiodobenzylguanidine and Tc-99m-sestamibi. ARIs were recorded during baseli ne sinus rhythm, norepinephrine (NE) infusion (0.1 mu g.kg(-1) min(-1)), an d left stellate ganglion stimulation (SS). NE shortened ARI in 98% of elect rodes in the denervated region. The degree of ART shortening and dispersion increased (P<0.001 and P<0.01, respectively) as denervation became more se vere. SS shortened ARI in 30% of electrodes in the denervated area, with in creased shortening and dispersion related to increased severity of denervat ion (P<0.01). SS prolonged ARI in 70% of electrodes in the denervated area, with no correlation with severity of denervation. Conclusions-The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulat ion: neural (SS) versus humoral (NE). The differences may relate to the con centration of NE released.