The effects of sympathetic denervation on spontaneous ventricular defibrillation in the rat

1992 ◽  
Vol 70 (6) ◽  
pp. 890-896
Author(s):  
Menashe B. Waxman ◽  
Arjun D. Sharma ◽  
John Asta ◽  
Laszlo Endrenyi

Ventricular tachycardia or ventricular fibrillation was electrically induced in 38 normal rats (group 1) and 24 sympathetically denervated rats (6-hydroxydopamine) (group 2). The time for spontaneous reversion to sinus rhythm was measured during (1) control, (2) isoproterenol, and (3) the combination of isoproterenol and phenylephrine. The time for spontaneous reversion was the same in both groups in the three states. The reversion time was prolonged threefold by isoproterenol, and restored to control values when phenylephrine was added to the infusion of isoproterenol. The tachycardia duration and the refractory period were inversely related: log10 (tachycardia duration) = 3.466 – 0.091 (refractory period). Ventricular tachycardia/fibrillation induction was examined as follows: (i) Ventricular tachycardia/fibrillation was induced in 100% of normal rats (group 1), but only 42% of the denervated rats (group 2, p < 0.001); (ii) during isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of rats of both groups; and (iii) when phenylephrine was added to isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of group 1 rats versus 82% of group 2 rats, (p = NS). These observations suggest (1) the induction of ventricular tachycardia/fibrillation is highly dependent on intact sympathetic innervation, and (2) exogenous adrenergic agonists modulate the duration of ventricular fibrillation through their effects on ventricular refractory period, independent of sympathetic innervation.Key words: spontaneous defibrillation, sympathetic denervation.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Borislav Dinov ◽  
Arash Arya ◽  
Valentina Schirripa ◽  
Livio Bertagnolli ◽  
Lukas Fiedler ◽  
...  

Introduction: Recent publications reported on higher recurrence rates and lack of survival benefit after catheter ablation (CA) of ventricular tachycardia (VT) in nonischemic dilated cardiomyopathy (NIDCM). Methods: We aimed to investigate the VT recurrence and cardiac mortality in patients with NIDCM ablated for VT. The studied cohort was divided in 2 groups depending on procedure success: complete success (group 1), and failure or incomplete success (group 2). Success definition was based on the VT inducibility after CA. The patients were prospectively followed for cardiac mortality and VT recurrence. Results: 104 patients with NIDCM (87 males, mean age 59.65 ± 14.69 years, mean ejection fraction 33.42 ± 11.42 %) underwent VT ablation. Ventricular stimulation after CA was not attempted in 13 (12.5%) patients. Out of the rest 91, complete success was achieved in 62 (68.1%) patients (group1), and incomplete success or failure in 29 (31.9%) patients (group 2). During 2-years follow-up, VT recurrence was observed in 56.5% in group 1 vs. 82.8% in group 2. Incomplete success was associated with higher VT recurrence (HR 1.91; 95% CI 1.13-3.22; p=0.015). The 2-years mortality was 14.5% in group 1 vs 34.5% in group 2. The probability for death was 3-times higher in group 2 (adjusted HR 3.18; 95% CI 1.18-8.56; p=0.022). The primary and secondary endpoints were comparable between patients with idiopathic, post-myocarditis and secondary NIDCM. Conclusion: Procedure success, defined as complete VT noninducibility after CA of VT, was associated with reduced VT recurrence and improved survival in patients with nonischemic dilated cardiomyopathy.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Mohanty ◽  
C Trivedi ◽  
D G Della Rocca ◽  
C Gianni ◽  
B MacDonald ◽  
...  

Abstract Introduction We investigated the ablation success of scar homogenization with combined (epicardial + endocardial) versus endocardial-only approach for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up. Method Consecutive ICM patients undergoing VT ablation at our center were classified into group 1: endocardial scar homogenization and group 2: endocardial +epicardial scar homogenization. Patients with previous open heart surgery were excluded. All patients underwent bipolar substrate mapping with standard scar settings defined as normal tissue &gt;1.5 mV and severe scar &lt;0.5 mV. Non-inducibility of monomorphic VT was the procedural endpoint in both groups. Patients were followed up twice a year for 5 years with implantable device interrogations. Results A total of 361 (Group 1: 291 and group 2: 70) patients were included in the study (mean age: 67 years, male: 88.4%). At 5 years, significantly higher number of patients from group 2 remained arrhythmia-free (figure 1). Of those patients, 87 (45%) and 51 (89%) from group 1 and 2 respectively were off-anti-arrhythmic drugs (AAD) (p&lt;0.001). After adjusting for age, gender, hypertension, diabetes, and obstructive sleep apnea, scar homogenization using endo-epicardial approach was associated with 51% less recurrence compared to the endocardial ablation strategy (Hazard Ratio: 0.49, 95% CI: 0.27–0.89, p: 0.02). Conclusion In this series of patients with ischemic cardiomyopathy and VT, endo-epicardial scar homogenization was associated with a lower need for AAD and a significantly lower recurrence rate at 5-years of follow-up compared to the endocardial ablation alone. FUNDunding Acknowledgement Type of funding sources: None. Figure 1


1998 ◽  
Vol 274 (4) ◽  
pp. H1113-H1120 ◽  
Author(s):  
Michael R. Ujhelyi ◽  
J. Jason Sims ◽  
Allison Winecoff Miller

This study assessed the effect of low (10 mg ⋅ kg−1 ⋅ h−1) and very high (18 mg ⋅ kg−1 ⋅ h−1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 ( n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 ( n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% ( P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values ( P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 ± 2.7 to 12.9 ± 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation ( P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values. However, there is a possibility that an unidentified action of lidocaine is responsible for these effects.


2017 ◽  
Vol 312 (3) ◽  
pp. H392-H405 ◽  
Author(s):  
Tadanobu Irie ◽  
Kentaro Yamakawa ◽  
David Hamon ◽  
Keijiro Nakamura ◽  
Kalyanam Shivkumar ◽  
...  

Cardiac sympathetic denervation (CSD) is reported to reduce the burden of ventricular tachyarrhythmias [ventricular tachycardia (VT)/ventricular fibrillation (VF)] in cardiomyopathy patients, but the mechanisms behind this benefit are unknown. In addition, the relative contribution to cardiac innervation of the middle cervical ganglion (MCG), which may contain cardiac neurons and is not removed during this procedure, is unclear. The purpose of this study was to compare sympathetic innervation of the heart via the MCG vs. stellate ganglia, assess effects of bilateral CSD on cardiac function and VT/VF, and determine changes in cardiac sympathetic innervation after CSD to elucidate mechanisms of benefit in 6 normal and 18 infarcted pigs. Electrophysiological and hemodynamic parameters were evaluated at baseline, during bilateral stellate stimulation, and during bilateral MCG stimulation in 6 normal and 12 infarcted animals. Bilateral CSD (removal of bilateral stellates and T2 ganglia) was then performed and MCG stimulation repeated. In addition, in 18 infarcted animals VT/VF inducibility was assessed before and after CSD. In infarcted hearts, MCG stimulation resulted in greater chronotropic and inotropic response than stellate ganglion stimulation. Bilateral CSD acutely reduced VT/VF inducibility by 50% in infarcted hearts and prolonged global activation recovery interval. CSD mitigated effects of MCG stimulation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts, without causing hemodynamic compromise. These data demonstrate that the MCG provides significant cardiac sympathetic innervation before CSD and adequate sympathetic innervation after CSD, maintaining hemodynamic stability. Bilateral CSD reduces VT/VF inducibility by improving electrical stability in infarcted hearts in the setting of sympathetic activation. NEW & NOTEWORTHY Sympathetic activation in myocardial infarction leads to arrhythmias and worsens heart failure. Bilateral cardiac sympathetic denervation reduces ventricular tachycardia/ventricular fibrillation inducibility and mitigates effects of sympathetic activation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts. Hemodynamic stability is maintained, as innervation via the middle cervical ganglion is not interrupted. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/anti-arrhythmic-mechanism-of-bilateral-stellectomy/ .


2016 ◽  
Vol 88 (8) ◽  
pp. 10-13 ◽  
Author(s):  
T Yu Rebrova ◽  
T M Ripp ◽  
S A Afanasiev ◽  
V F Mordovin ◽  
E F Muslimova

Aim. To investigate time course of changes in the adrenoreactivity (AR) of erythrocyte membranes (EM) after radiofrequency ablation of the synaptic nerves of the renal arteries (RA) in patients with resistant hypertension (RH) and to assess whether this indicator can be used for the early evaluation of the efficiency of an invasive intervention into the RA. Subjects and methods. 24 patients with RH, who received full-dose antihypertensive therapy with at least three drugs, including a diuretic, were examined. Renal sympathetic denervation (RSD) was carried out by endovascular radiofrequency ablation (RFA) of the RA. 24-hour blood pressure (BP) monitoring and determination of the β-adrenoreactivity (β-AR) of EM were performed, by taking into account the change in erythrocyte osmoresistence at baseline and 1 and 24 weeks after RFA. The therapy was not changed during the observation. Results. The patients included in the study were divided into 2 groups. One week following RSD, 15 patients of Group 1 were noted to have a decrease in the β-AR of EM by 10 conditional units or more; average daily systolic BP (SBP) and diastolic BP (DBP) reduced by 8.3 and 2.8 mm Hg, respectively. In 9 patients of Group 2, the β-AR of EM was unchanged in this observation period or increased compared with baseline. In this group, the decrease in average daily SBP and DBP was noted to be less pronounced than that in Group 1 (by 1.4 and 1.5 mm Hg, respectively). At 24 weeks after RSD, Group 1 was seen to have an effective daily decrease in average daily SBP and DBP by 25.6 and 14.3 mm Hg, respectively (p=0.01 and 0.05). The average value of the β-AR of EM significantly declined compared with baseline. In Group 2, no statistically significant changes were reported; SPB and DBP lowered by 7.0 and 3.0 mm Hg, respectively. There was a significant decrease in the β-AR of EM compared with that at week 1. Conclusion. The decline in the β-AR of EM within the first week after RFA is suggestive of the decreased activity of the sympathoadrenal system and may be used as an early efficiency index of RSD after the procedure.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
C Jungen ◽  
HS Chen ◽  
Y Kimura ◽  
P Dibbets-Schneider ◽  
SRD Piers ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - Projektnummer 447558597) Background Among patients with non-ischemic cardiomyopathy (NICM) two dominant ventricular tachycardia (VT) substrate locations, namely anteroseptal (AS) and inferolateral (IL), have been identified. The poor outcome after catheter ablation of AS substrates (ASS) compared to IL substrates (ILS) has been attributed to its deep intramural location. However, region specific tissue charateristics, including sympathetic innervation, as important determinant of arrhythmogeneity, may also contribute to the outcome disparity. Aim To evaluate the association between regional sympathetic denervation, myocardial fibrosis and VT substrates according to two dominant VT substrate locations. Methods Twenty-nine patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent electroanatomical substrate mapping and radiofrequency catheter ablation (RFCA), LGE-CMR and 123-I-MIBG imaging between 2011-2018 were included. The 16-segment model was used to describe the distribution of endocardial low unipolar voltage (UV &lt;25th IQR) (=electroanatomical surrogate for fibrosis), the location of abnormal local electrograms and VT related sites (= surrogate for VT substrate) and the presence of LGE. Regional cardiac sympathetic innervation was determined by 123-I-MIBG imaging and analyzed according to the 16-segment model. Regions with sympathetic denervation were correlated with low UV areas, VT substrate location and LGE. Patients were categorized according to the dominant VT substrate location in ASS or ILS. Results Ten patients had a dominant ASS, 12 patients a dominant ILS and 1 patient had ASS and ILS; 6 patients had other VT substrate locations. All but one patient with ASS and one with ILS also showed corresponding low UV (=surrogate for fibrosis) in segments with VT substrates. Eight patients with IL VT substrates but only 4 with AS substrates showed corresponding LGE in the VT related segments. All patients with inferolateral VT substrates showed sympathetic denervation in IL segments (100% matching segments), but only 3/11 (27%) with anteroseptal substrates had sympathetic denervation in AS segments (P = 0.0002). UV was not significantly different between matching (VT substrate and denervation) and not matching ASS segments (5.74 ± 2.69 mV vs. 4.64 ± 1.85 mV, P = 0.78) and between matching ASS and ILS segments (5.74 ± 2.69 mV vs. 7.61 ± 2.91, P = 0.43). LGE location was matching with sympathetic denervation in all patients with ILS but only in 33% of patients with ASS. Conclusion Despite low endocardial UV (=surrogate for fibrosis) for AS and IL segments harboring VT substrates, regional sympathetic denervation coincided with fibrosis only for IL VT substrates. The mismatch between regional fibrosis and preserved innervation for AS VT substrates may contribute to a VT substrate difficult to control by RFCA.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Bing Huang ◽  
Lilei Yu ◽  
Bo He ◽  
Zhibing Lu ◽  
Songyun Wang ◽  
...  

Introduction: Previous studies suggest that renal sympathetic nerves can modulate central sympathetic tone. Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with different settings of ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear. Methods: Twenty-eight adult mongrel dogs were included in the present study. Eighteen dogs were subjected to RSD which was performed by ablating the adventitial surface of the renal artery. In Group 1 (n=8), programmed stimulation was performed before and after RSD to determinate ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. In Group 2 (n=10), acute myocardial ischemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD and the incidence of ventricular arrhythmia (VA) was calculated during 1-hour recording. In another 10 dogs (Group 3), AMI was induced and VA was measured with sham RSD. Results: In Group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximum slope (Smax) of the restitution curve and suppressed APD alternans at each site (Fig. 1A, C, E). RSD also significantly decreased the spatial dispersions of ERP, APD and Smax (Fig. 1B, D, F). The occurrence of spontaneous VA during 1-h AMI in Group 2 was significantly lower than that in Group 3 (Tab. 1). Conclusions: RSD significantly prolongs ventricular ERP and APD, attenuates APD restitution properties and reduces the incidence of ischemia-induced VA, suggesting that RSD may exert an anti-arrhythmic role for VA.


2008 ◽  
Vol 86 (10) ◽  
pp. 700-709 ◽  
Author(s):  
Juan Bai ◽  
Chongyu Ren ◽  
Wei Hao ◽  
Rui Wang ◽  
Ji-Min Cao

Sympathetic denervation is frequently observed in heart disease. To investigate the linkage of sympathetic denervation and cardiac arrhythmia, we developed a rat model of chemical sympathectomy by subcutaneous injections of 6-hydroxydopamine (6-OHDA). Cardiac sympathetic innervation was visualized by means of a glyoxylic catecholaminergic histofluorescence method. Transient outward current (Ito) of ventricular myocytes was recorded with the whole-cell configuration of the patch clamp technique. We observed that sympathectomy (i) decreased cardiac sympathetic nerve density and norepinephrine level, (ii) reduced the protein expression of Kv4.2, Kv1.4, and Kv channel-interacting protein 2 (KChIP2), (iii) decreased current densities and delayed activation of Ito channels, (iv) reduced the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element-binding protein (CREB), and (v) increased the severity of ventricular fibrillation induced by rapid pacing. Three weeks after 6-OHDA injections, which allowed time for sympathetic regeneration, we found cardiac sympathetic nerve density, norepinephrine levels, expression levels of Kv4.2 and KChIP2 proteins, and Ito densities were partially normalized and ventricular fibrillation severity was decreased. We conclude that chemical sympathectomy downregulates the expression of selective Kv channel subunits and decreases myocardial Ito channel activities, contributing to the elevated susceptibility to ventricular fibrillation.


Author(s):  
Oscar Cano ◽  
Víctor Pérez-Roselló ◽  
Hebert Ayala ◽  
Maite Izquierdo de Francisco ◽  
Joaquín Osca ◽  
...  

Introduction:Stand-alone substrate ablation without baseline ventricular tachycardia (VT) induction and activation mapping has become a standard VT ablation strategy. We sought to evaluate the influence of baseline VT inducibility and activation mapping on ablation outcomes in patients with structural heart disease (SHD) undergoing VT ablation. Methods:This is a single center, observational and retrospective study including consecutive patients with SHD and documented VT undergoing ablation. Baseline VT induction was attempted before ablation in all patients and VT activation mapping performed when possible. Ablation was guided by activation mapping for mappable VTs plus substrate ablation for all patients. Ablation outcomes and complications were evaluated. Results: 160 patients were included (203 VT ablation procedures) and were classified in 3 groups according to baseline VT inducibility: group 1 (non inducible, n=18), group 2 (1 VT morphology induced, n=53), and group 3 (>1VT morphology induced, n=89). VT activation mapping was possible in 35%. After a median follow-up of 38.5 months, baseline inducibility of >1VT morphology was associated with a significant incidence of VT recurrence (42% for group 3 vs. 15.1% for group 2 and 5.6% for group 1, Log-rank p<0.0001) and activation mapping with a lower rate of VT recurrence (24% vs. 36.3%, Log-rank p=0.035). Independent predictors of VT recurrences and mortality were baseline inducibility of >1VT morphology (HR 12.05 IC 95% 1.60-90.79, p=0.016) and LVEF<30% (HR 2.43 IC 95% 1.45-4.07, p=0.001), respectively. Complications occurred in 11.2% (5.6% hemodynamic decompensation). Conclusions:Baseline VT inducibility and activation mapping may add significant prognostic information during VT ablation procedur


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