Heterogeneous Sympathetic Innervation Influences Local Myocardial Repolarization in Normally Perfused Rabbit Hearts

Abstract

Background-Heterogeneity of sympathetic innervation is thought to contribute 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 recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [ 125 I]metaiodobenzylguanidine and 99m Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased (PϽ0.001 and PϽ0.01, respectively) as denervation became more severe. SS shortened ARI in 30% of electrodes in the denervated area, with increased shortening and dispersion related to increased severity of denervation (PϽ0.01). 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 stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

The Role of the Autonomic Nervous System in Sudden Cardiac Death

“…Interestingly, they show evidence of norepinephrine depletion on histologic and histofluorescent catecholamine analysis, although they appear to be histologically normal. These studies were confirmed by Yoshioka et al 34 in rabbits with regional denervation due to application of phenol. Activation recovery interval (ARI), a surrogate of ERP, was used in these studies to show that norepinephrine infusion shortened ARI in 98% of denervated regions, with increase in both shortening and dispersion of ARI in more severely denervated regions.…”

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

“…Heterogeneous intramyocardial sympathetic nerve sprouting at scar border zones leads to labile repolarization, increased peak Ca 2ϩ current, and susceptibility to ventricular fibrillation in hypercholesterolemic rabbits (15). Increased transmural dispersion of repolarization has also been reported (13,28), along with alterations in transient outward and inward rectifier K ϩ currents (21) in a postinfarct model with nerve sprouts.…”

Nifekalant Hydrochloride Administration During Cardiopulmonary Resuscitation Improves the Transmural Dispersion of Myocardial Repolarization Experimental Study in a Canine Model of Cardiopulmonary Arrest

“…RT extends from the start of the QRS wave to the maximum differential of the T wave (ie, sum of AT and ARI) and it was used as an index of the time from the depolarization to repolarization. 10 All of the measurements were made in 3 consecutive heartbeats during sinus rhythm, and the mean values were calculated. ARID was calculated as the difference between the maximal ARI (max-ARI) and the minimum ARI (min-ARI) in the 64 measurement regions, and it was used as an index of the 2-dimensional dispersion on the heart's surface.…”

“…Antzelevitch et al have reported on the effect of class III drugs on the TDR in wedge models in normal dogs. 10,19,20 Sicouri et al stated that chronic oral administration of AMD in dogs reduced the TDR by causing APD prolongation in the epicardium and endocardium of the LV, and APD shortening in M cells. 19 On the other hand, when they administered IKr blockers, such as E-4031, and d-sotalol, there was a relative increase in the TDR as a result of preferential APD prolongation in the M cells.…”

“…21 Moreover, another report using living dogs stated that the incidence of adrenaline-induced TdP was increased by the combined effect of MS-551 and an , -receptor agonist (adrenaline). 22 Even if a -receptor agonist is administrated alone without NIF, once myocardial ischemia develops, -adrenaline sensitivity becomes locally inhomogeneity at the epicardial border zone, 10 and causes alternation of the RPT with each heartbeat in addition to spatial dispersion. However, in the present study we did not see alternation of the RPT when NIF was administered after epinephrine (data not shown) and we consider that one of the reasons for this result is the background conditions of the CPA.…”