Heterogeneous Sympathetic Innervation in German Shepherd Dogs With Inherited Ventricular Arrhythmia and Sudden Cardiac Death

Dae, Michael W.; Lee, R J; Ursell, Philip C.; Chin, Michael C.; Stillson, Carol; Moı̈se, N. Sydney

doi:10.1161/01.cir.96.4.1337

Cited by 81 publications

(48 citation statements)

References 28 publications

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“…1,2 Heterogeneity in the spatial distribution and activity of sympathetic innervation is also thought to contribute to the potential for fatal arrhythmia, possibly through effects on reentry. 3,4 Recently, several investigations have suggested a relationship between regional neuronal dysfunction and ventricular arrhythmia in humans 5,6 and animals 7,8 in the absence of infarction or perfusion abnormalities. Denervation supersensitivity to circulating catecholamines has been implicated in the pathogenesis of these arrhythmias.…”

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confidence: 99%

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

et al. 2000

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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.

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

et al. 2000

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“…[1][2][3][4][5][6] Although the importance of the autonomic nervous system in atrial fibrillation (AF) has been suggested by both experimental and clinical observations, its role in the initiation and perpetuation of AF has not been determined. The autonomic tone before the onset of AF has been used to identify so-called vagal AF in humans.…”

mentioning

confidence: 99%

“…[11][12][13][14][15] One potential mechanism for this spatial dispersion of refractoriness is heterogeneity of autonomic innervation. 16 -20 This heterogeneity has been shown to be an important mechanism in ventricular arrhythmias [1][2][3][4][5][6]21,22 and has been hypothesized to be important in atrial arrhythmogenesis.…”

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confidence: 99%

Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

et al. 1998

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Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation.

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“…26 In addition, heterogeneity of ventricular repolarization because of heterogeneous sympathetic innervation after MI may have a potential arrhythmogenic effect. [27][28][29] A previous study demonstrated that ventricular arrhythmias occurring in patients who had suffered MI were associated with increased mortality during the follow-up period. 30 In a multicenter study, paired VPCs after MI were associated with a more than 3-fold increase in the odds ratio of mortality compared with those with no VPC, and ventricular tachycardia with a 5-to 6-fold increase in the odds ratio.…”

Section: Effect Of Pc On Ventricular Arrhythmiasmentioning

confidence: 99%

Brief Episode of Myocardial Ischemia Before Prolonged Ischemia Attenuates Cardiac Sympathetic Nerve Injury

Nakadate

Nozawa

Matsuki

et al. 2006

Circ J

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Background The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. Methods and Results Sympathetic neural function was assessed using 123 I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1±4.0 vs 0.4±4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3±2.3 vs 18.6±5.9 ×10 3 pg/ml, p<0.01) and MIBG uptake of ischemic region was greater (0.061±0.029 vs 0.031±0.011 %kg dose/g, p<0.05) compared with rats without the pretreatment. Conclusion A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.

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Heterogeneous Sympathetic Innervation in German Shepherd Dogs With Inherited Ventricular Arrhythmia and Sudden Cardiac Death

Abstract: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.

Cited by 81 publications

References 28 publications

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

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

Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation

Brief Episode of Myocardial Ischemia Before Prolonged Ischemia Attenuates Cardiac Sympathetic Nerve Injury

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