Quantitative assessment of transient autonomic modulation after single-shot pulmonary vein isolation with pulsed-field ablation.

INTRODUCTION: Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed-field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the FarapulseTM PFA system during PVI compared with single-shot thermal ablation. METHODS: A total of 76 patients underwent first-time PVI with either FarapulseTM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2). RESULTS: Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706-1090] ms, p < .001 compared to baseline; PFA group: 11 466 [8720-12 293] ms, p = .70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p = .001). Moreover, heart rate 24 h post-PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p < .001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p < .001 compared to baseline), which recovered almost completely within 10 min. CONCLUSION: PVI with the FarapulseTM PFA system is associated with only transitory and short-lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated.

Lack of evidence for impaired preload or Bezold-Jarisch activation during brief umbilical cord occlusions in fetal sheep.

Impaired cardiac preload secondary to umbilical cord occlusion (UCO) has been hypothesized to contribute to intrapartum decelerations, brief falls in fetal heart rate (FHR), through activation of the Bezold-Jarisch reflex. This cardioprotective reflex increases parasympathetic and inhibits sympathetic outflows triggering hypotension, bradycardia, and peripheral vasodilation, but its potential to contribute to intrapartum decelerations has never been systematically examined. In this study, we performed bilateral cervical vagotomy to remove the afferent arm and the efferent parasympathetic arm of the Bezold-Jarisch reflex. Twenty-two chronically instrumented fetal sheep at 0.85 of gestation received vagotomy (n = 7) or sham vagotomy (control, n = 15), followed by three 1-min complete UCOs separated by 4-min reperfusion periods. UCOs in control fetuses were associated with a rapid fall in FHR and reduced femoral blood flow mediated by intense femoral vasoconstriction, leading to hypertension. Vagotomy abolished the rapid fall in FHR (P < 0.001) and, despite reduced diastolic filling time, increased both carotid (P < 0.001) and femoral (P < 0.05) blood flow during UCOs, secondary to carotid vasodilation (P < 0.01) and delayed femoral vasoconstriction (P < 0.05). Finally, vagotomy was associated with an attenuated rise in cortical impedance during UCOs (P < 0.05), consistent with improved cerebral substrate supply. In conclusion, increased carotid and femoral blood flows after vagotomy are consistent with increased left and right ventricular output, which is incompatible with the hypothesis that labor-like UCOs impair ventricular filling. Overall, the cardiovascular responses to vagotomy do not support the hypothesis that the Bezold-Jarisch reflex is activated by UCO. The Bezold-Jarisch reflex is therefore mechanistically unable to contribute to intrapartum decelerations.

Relationship between microvascular changes, autonomic denervation, and myocardial fibrosis in Chagas cardiomyopathy: Evaluation by MRI and SPECT imaging.

BACKGROUND: The relationship between microvasculopathy, autonomic denervation, and myocardial fibrosis, in Chagas cardiomyopathy is incompletely understood. The aim of this study was to explore the relative extent and anatomic distribution of myocardial hypoperfusion, autonomic denervation, and myocardial scarring using Single-Photon Emission Computerized Tomography (SPECT) imaging and Magnetic Resonance Imaging (MRI). METHODS: Thirteen patients with Chagas disease all had Iodine-123-metaiodobenzylguanidine (MIBG) SPECT, 99mTc-Sestamibi (MIBI) rest-stress SPECT, and gadolinium late enhancement MRI imaging within a 2-month interval. The anatomic location and extent of denervation, of stress-induced hypoperfusion and fibrosis, were assessed through image co-registration and quantification of abnormal tissue areas as a percent of total myocardium. RESULTS: The results showed a strong general anatomic concordance between areas of hypoperfusion, denervation, and fibrosis, suggesting that the three abnormal features may be correlated. Myocardial denervation was anatomically and quantitatively closely associated areas of stress hypoperfusion. CONCLUSION: Combined myocardial analysis of the extent and location of autonomic denervation, hypoperfusion, and scarring may allow for better understanding of the pathophysiology of Chagas cardiomyopathy. Autonomic myocardial denervation may be a more sensitive marker of cardiac involvement in Chagas Disease than finding by other imaging modalities.

Effects of renal denervation on blood pressure in hypertensive patients with end-stage renal disease: a single centre experience.

BACKGROUND: Sympathetic nerve activity is a hallmark of hypertension in end-stage renal disease (ESRD). An initial proof-of-concept study implies that renal denervation (RDN) is feasible and safe in RDN, but overall data are limited. METHODS: In this single-centre prospective pilot study six patients with ESRD and treatment resistant hypertension were consecutively included. Ambulatory blood pressure (ABP) was measured before and 6 months after RDN (Symplictiy Flex™, Medtronic Inc., Santa Rosa, CA). Moreover, haemodialysis parameters which may affect BP reduction were monitored closely. RESULTS: In all patients bilateral RDN was successful done, without documentation of peri- or postprocedural complications. There was a significant reduction in 24-h ABP by 20 ± 17/15 ± 12 mmHg 6 months after RDN (systolic: 163 ± 16 versus 143 ± 9 mmHg, p = 0.043; diastolic: 96 ± 9 versus 81 ± 15 mmHg, p = 0.043), with similar results for day-, and nighttime values, respectively. Antihypertensive medication was kept stable as well as there was no change in haemodialysis parameters during follow-up. In addition, ultrafiltration/week (1.4 ± 1.4 versus 2.2 ± 1.4 l, p = 0.08) as well as hematocrit (measured at baseline and 6 months after RDN) (33.7 ± 4.3 versus 33.1 ± 3.9%, p = 0.715) revealed no change in volume status. CONCLUSION: Our single-centre pilot study not only supports current data on renal safety of RDN even in small arteries of patients with ESRD, but also enhances the knowledge towards an effective ABP reduction in this type of hypertensive patients.

Neuromodulation Approaches for Cardiac Arrhythmias: Recent Advances.

PURPOSE OF REVIEW: This review aims to describe the latest advances in autonomic neuromodulation approaches to treating cardiac arrhythmias, with a focus on ventricular arrhythmias. RECENT FINDINGS: The increasing understanding of neuronal remodeling in cardiac diseases has led to the development and improvement of novel neuromodulation therapies targeting multiple levels of the autonomic nervous system. Thoracic epidural anesthesia, spinal cord stimulation, stellate ganglion modulatory therapies, vagal stimulation, renal denervation, and interventions on the intracardiac nervous system have all been studied in preclinical models, with encouraging preliminary clinical data. The autonomic nervous system regulates all the electrical processes of the heart and plays an important role in the pathophysiology of cardiac arrhythmias. Despite recent advances in the clinical application of cardiac neuromodulation, our comprehension of the anatomy and function of the cardiac autonomic nervous system is still limited. Hopefully in the near future, more preclinical data combined with larger clinical trials will lead to further improvements in neuromodulatory treatment for heart rhythm disorders.

The Effect of Neuroscientists on the Studies of Autonomic Nervous System Dysfunction Following Experimental Subarachnoid Hemorrhage.

OBJECTIVE: The autonomic nervous system dysfunctions following subarachnoid hemorrhage (SAH) are common in neurosurgical clinical practice. The aim of the study is to investigate the effect of Asian neuroscientists on the studies of autonomic nervous system dysfunction following experimental subarachnoid hemorrhage. METHODS: A systematic search was conducted using the MEDLINE and Web of Science databases for studies pertaining to SAH and autonomic nervous system dysfunction. The searched terms contained "experimental subarachnoid hemorrhage," "autonomic nervous system," and "Ganglion." RESULTS: There are many animal studies because the live human brain vessels cannot be used in investigations. The considerable efforts have been made to investigate the effect of SAH on the autonomic nervous system in laboratory animals. Seventy-four studies were published by various authors. Most of the articles came from Asian Countries 49 studies (66.2% of the total studies). The most preferred animals were rabbits (in 43 studies, 58.1% of the total studies). CONCLUSION: Asian neuroscientists published enormous contributions in SAH-related autonomic nervous system dysfunction. It was shown that there is a great interest of Asian neuroscientists for autonomic nervous system changes secondary to SAH.

Long-term follow-up of treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorraphy: a new technique.

OBJECTIVE: To study a novel penile reinnervation technique using four sural nerve grafts and end-to-side neurorraphies connecting bilaterally the femoral nerve and the cavernous corpus and the femoral nerve and the dorsal penile nerves. PATIENTS AND METHODS: Ten patients (mean [± sd; range] age 60.3 [± 4.8; 54-68] years), who had undergone radical prostatectomy (RP) at least 2 years previously, underwent penile reinnervation in the present study. Four patients had undergone radiotherapy after RP. All patients reported satisfactory sexual activity prior to RP. The surgery involved bridging of the femoral nerve to the dorsal nerve of the penis and the inner part of the corpus cavernosum with sural nerve grafts and end-to-side neurorraphies. Patients were evaluated using the International Index of Erectile Function (IIEF) questionnaire and pharmaco-penile Doppler ultrasonography (PPDU) preoperatively and at 6, 12 and 18 months postoperatively, and using a Clinical Evolution of Erectile Function (CEEF) questionnaire, administered after 36 months. RESULTS: The IIEF scores showed improvements with regard to erectile dysfunction (ED), satisfaction with intercourse and general satisfaction. Evaluation of PPDU velocities did not reveal any difference between the right and left sides or among the different time points. The introduction of nerve grafts neither caused fibrosis of the corpus cavernosum, nor reduced penile vascular flow. CEEF results showed that sexual intercourse began after a mean of 13.7 months with frequency of sexual intercourse varying from once daily to once monthly. Acute complications were minimal. The study was limited by the small number of cases. CONCLUSIONS: A total of 60% of patients were able to achieve full penetration, on average, 13 months after reinnervation surgery. Patients previously submitted to radiotherapy had slower return of erectile function. We conclude that penile reinnervation surgery is a viable technique, with effective results, and could offer a new treatment method for ED after RP.

Long-Term Oncological Outcome After Conventional Radical Hysterectomy Versus 2 Nerve-Sparing Modalities for Early Stage Cervical Cancer.

OBJECTIVES: Nerve-sparing radical hysterectomy for early stage cervical cancer was introduced to improve quality of life after treatment. Sparing the pelvic autonomic nerves reduces bladder, bowel, and sexual dysfunction. The Leiden nerve-sparing radical hysterectomy (LNSRH) was modified to the Swift procedure, the latter being more radical regarding the sacrouterine and parametrial resection. We investigate whether nerve-sparing surgery has comparable oncological outcomes as the conventional radical hysterectomy (CRH). Concurrently, we investigate whether there is a difference regarding the oncological outcomes of the 2 nerve-sparing techniques. METHODS: This is a single-center, observational prospective cohort study analyzing oncological outcomes in women undergoing CRH (1994-1999), LNSRH (2001-2005), or Swift procedure (2006-2010) for early stage cervical cancer (International Federation of Gynecology and Obstetrics IA2-IIA). RESULTS: Three hundred sixty-three patients (124 CRH, 122 LNSRH, and 117 Swift) were included. International Federation of Gynecology and Obstetrics stage IB2 or higher (P = 0.005) was significantly more prevalent in the CRH cohort. The 5-year pelvic relapse-free survival and overall survival were not significantly different between the 3 cohorts (P = 0.116). Regarding the nerve-sparing cohorts, the Swift cohort showed a significant better 5-year overall survival (87.2%) compared with the LNSRH cohort (78.8%) (P = 0.04). In the LNSRH cohort, resection planes less than 5 mm free and need for adjuvant therapy were significantly higher than in the Swift cohort (P = 0.026 and 0.046, respectively). CONCLUSIONS: The nerve-sparing radical hysterectomy shows a similar oncological outcome compared with the CRH. The more radical Swift version of nerve-sparing techniques is preferable to the former LNSRH procedure.

Intraoperative nerve staining in nerve-sparing radical hysterectomy: a pilot study.

OBJECTIVE: To evaluate the feasibility and effectiveness of intraoperative nerve staining by modified leucomethylene blue (MLB). METHODS: Animal experiment was performed to assure whether the tissues dyed blue by MLB were nerves with microscopic examination. Ten patients with cervical cancer were performed by nerve-sparing radical hysterectomy (NSRH) and nerve staining intraoperatively by MLB. The status of staining was recorded. The post-void residual urine volume after removing was measured by ultrasound. The time to post-void residual urine volume of less than 100 ml and the first defecation were recorded. RESULTS: In animal experiment, the tissues dyed blue obviously showed abundant nerve fibers by microscopic examination. The minor nerves were dyed blue clearly in NSRH. The time to post-void residual urine volume of less than 100 ml after removal of the urethral catheter was 10.3 (7-13) days by records. The time to the first defecation was 67.7 (60-82) h. CONCLUSION: Intraoperative nerve staining by MLB provided a new method for nerve location in NSRH. It was safe, effective and convenient.

Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy.

Autonomic nervous system activation can induce significant and heterogeneous changes of atrial electrophysiology and induce atrial tachyarrhythmias, including atrial tachycardia and atrial fibrillation (AF). The importance of the autonomic nervous system in atrial arrhythmogenesis is also supported by circadian variation in the incidence of symptomatic AF in humans. Methods that reduce autonomic innervation or outflow have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. In this review, we focus on the relationship between the autonomic nervous system and the pathophysiology of AF and the potential benefit and limitations of neuromodulation in the management of this arrhythmia. We conclude that autonomic nerve activity plays an important role in the initiation and maintenance of AF, and modulating autonomic nerve function may contribute to AF control. Potential therapeutic applications include ganglionated plexus ablation, renal sympathetic denervation, cervical vagal nerve stimulation, baroreflex stimulation, cutaneous stimulation, novel drug approaches, and biological therapies. Although the role of the autonomic nervous system has long been recognized, new science and new technologies promise exciting prospects for the future.

Ruptured blebs and racing hearts: autonomic cardiac changes in neurosurgeons during microsurgical clipping of aneurysms.

INTRODUCTION: In this study, we intend to evaluate the autonomic changes occurring in neurosurgeons and thus the stress during microsurgical clipping of aneurysms. AIMS AND OBJECTIVES: The aim of the current study is to evaluate the heart rate variability (HRV) of the neurosurgeons during microsurgical clipping of aneurysm by using continuous real time monitoring of the ECG intraoperatively. MATERIAL AND METHODS: Lead II ECG was recorded using Bioharness(®) (Zephyr Technologies, Annapolis, MD) in 4 healthy neurosurgeons who performed 29 microsurgical clipping of aneurysms. ECG from 21 surgeries was analysed (LabChart(®) software, ADInstruments, Dunedin, New Zealand) across five stages: Baseline (BL), sylvian fissure dissection (SFD), perianeurysmal dissection (PAD), clipping of the aneurysm (CLIP) and haemostasis (HEMO). RESULTS: There was a reduction in TP and an increased LF/HF ratio in spite of suppression of both LF and HF powers. Contrary to the common understanding that the sympathetic limb of the autonomic system mostly mediates responses during stress and anxiety, we found that there was a significant contribution of the parasympathetic system too.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Interventional and device-based autonomic modulation in heart failure.

"Heart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapies have sought to restore autonomic balance by neuromodulation. Results of preclinical animal studies and early clinical trials have demonstrated the safety and efficacy of these therapies in heart failure. This article discusses specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy, and renal sympathetic nerve denervation."

Localisation and preservation of the autonomic nerves in rectal cancer surgery - technical details.

Iatrogenic surgical injury to pelvic autonomic nerves followed by genitourinary dysfunctions are well known problems after total partial mesorectal excision for rectal cancer. The purpose of our paper is to present the useful anatomical landmarks for a safe nerve-sparing surgery in rectal oncology. Over the course of a total mesorectal excision we describe and illustrate the key risk zones of autonomic nerve injury based on our experience in rectal surgery and on the revised literature.

The autonomic nervous system regulates postprandial hepatic lipid metabolism.

The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P = 0.008), and VLDL-TG production tended to be increased (P = 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in >70% higher plasma triglycerides during the day (P = 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions.

Role of trigeminal microvascular decompression in the treatment of SUNCT and SUNA.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are primary headache disorders. Evidence suggests that SUNCT/SUNA have similar pathophysiology to the trigeminal autonomic cephalalgias and involves the trigeminal autonomic reflex. This review provides an overview of microvascular decompression of the trigeminal nerve and other surgical therapeutic options for SUNCT/SUNA. We have undertaken a mini-meta-analysis of available case reports and case series with the aim of providing recommendations for the use of such therapies in SUNCT/SUNA. There is some evidence supporting microvascular decompression of the trigeminal nerve in selected patients who have medically refractory SUNCT/SUNA and a demonstrable ipsilateral aberrant vessel on magnetic resonance imaging (MRI). We also consider what further investigations could be undertaken to assess the role of surgical interventions in the treatment of these often debilitating conditions.

[Anatomy and physiology of autonomic pelvic innervations].

Autonomic innervation is responsible for the correct function of the organs in the pelvis. Retroperitoneal surgery is associated with trauma of the nerve structures. For this reason a detailed knowledge of topographic anatomy of the pelvis is needed, when surgery for oncological diseases or endometriosis is performed. Faster recovery, decrease of the number of postoperative complications and a better quality of life are the result of the nerve-sparing approach.

[Application status and progress of intraoperative nerve monitoring in pelvic autonomic nerve preserving radical resection of rectal cancer].

The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.

Efficacy of cardiac autonomic denervation for atrial fibrillation: a meta-analysis.

INTRODUCTION: Adjunctive complex fractionated atrial electrograms (CFAE) ablation or ganglionated plexi (GP) ablation have been proposed as new strategies to increase the elimination of AF, but the difference between CFAE/GP ablation and pulmonary vein isolation (PVI), as well as the combined effect of CFAE/GP plus PVI ablation were unclear. This meta-analysis was designed to determine whether adjunctive cardiac autonomic denervation (CAD) was effective for the elimination of AF, and whether CAD alone was superior to PVI in AF patients. METHODS: A systemic literature search in MEDLINE, EMBASE, and Cochrane Controlled Trials Register (CCRT) was performed and controlled trials comparing the effect of PVI plus CFAE/GP ablation with PVI, as well as CFAE/GP ablation with PVI were collected. RESULTS: A total of 15 trials including 1,147 patients with AF were qualified for this meta-analysis. CAD plus PVI significantly increased the freedom from AF/ATs (OR 1.85, 95% CI: 1.33-2.59, P = 0.29). Subgroup analysis showed that additional CAD increased the ratio of sinus rhythm maintenance in both paroxysmal AF (OR 1.69; 95% CI: 1.09-2.62, P = 0.41) and nonparoxysmal AF (OR 2.11, 95% CI: 1.14-3.90, P = 0.14). Besides, when compared respectively, adjunctive CAD was not superior to PVI (OR 0.31; 95% CI: 0.11-0.86, P = 0.002). CONCLUSION: This study suggested that CAD plus PVI significantly increase the freedom from recurrence of AF both in paroxysmal and nonparoxysmal patients. However, when compared alone, the benefit of CAD was not superior to PVI.