Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 µs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory.

Imaging of Thoracic Neurogenic Tumors.

OBJECTIVE: Thoracic neurogenic neoplasms may be a diagnostic challenge both clinically and radiologically, ranging from benign, incidentally discovered tumors to aggressive, symptomatic malignancies. These tumors may originate from any nervous structure within the chest and are derived from cells of the nerve sheath, autonomic ganglia, or paraganglia. The nervous anatomy of the thorax is complex, and neurogenic tumors may be found in any mediastinal compartment or in the chest wall. Furthermore, neurogenic tumors may indicate one of many syndromes, particularly when they are multiple. CONCLUSION: This article illustrates the complex anatomy of the nervous system within the chest and details important epidemiologic and pathophysiologic features as an approach to neurogenic tumors of the thorax. Key imaging features of neurogenic tumors occurring in the chest are identified, focusing on distinguishing characteristics and the relative advantages of available imaging modalities to further refine a differential diagnosis.

Thoracic duct relationships to abnormal neurovascular structures in cervicothoracic regions: case study and clinical relevance.

The presence of variant intercostal and bronchial arteries and variable position of left recurrent laryngeal nerve (LRLN) along the course of thoracic duct (TD) may have clinical relevance in various cervicothoracic surgeries.

The heart and pericardium.

This article describes the normal anatomy of the heart and pericardium. Included is a detailed description of the pericardium, mediastinal nerves, cardiac chambers, valves, coronary arteries and veins, and the conduction tissues. As cardiac and thoracic surgery continue to get more specialized and the procedures become less invasive, it is essential for the cardiothoracic surgeon to have a thorough working knowledge of cardiothoracic anatomy.

Nerves of the mediastinum.

Knowledge of the anatomy of the mediastinal nerves is essential for the evaluation and surgical treatment of most thoracic neoplasms. Thorough knowledge of the normal anatomy of the mediastinal nerves and of their variants cannot be overestimated because nerve trauma during nerve anatomy is also important because mediastinal or lung tumors can locally infiltrate those nerves either directly or through nodal metastases, making them generally unresectable.

Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart.

BACKGROUND: Both normal and genetically modified mice are excellent models for investigating molecular mechanisms of arrhythmogenic cardiac diseases that may be associated with an imbalance between sympathetic and parasympathetic nervous input to the heart. OBJECTIVE: The purpose of this study was to (1) determine the structural organization of the mouse cardiac neural plexus, (2) identify extrinsic neural sources and their relationship with the cardiac plexus, and (3) reveal any anatomic differences in the cardiac plexus between mouse and other species. METHODS: Cardiac nerve structures were visualized using histochemical staining for acetylcholinesterase (AChE) on whole heart and thorax-dissected preparations derived from 25 mice. To confirm the reliability of staining parasympathetic and sympathetic neural components in the mouse heart, we applied a histochemical method for AChE and immunohistochemistry for tyrosine hydroxylase (TH) and/or choline acetyltransferase (ChAT) on whole mounts preparations from six mice. RESULTS: Double immunohistochemical labeling of TH and ChAT on AChE-positive neural elements in mouse whole mounts demonstrated equal staining of nerves and ganglia for AChE that were positive for both TH and ChAT. The extrinsic cardiac nerves access the mouse heart at the right and left cranial veins and interblend within the ganglionated nerve plexus of the heart hilum that is persistently localized on the heart base. Nerves and bundles of nerve fibers extend epicardially from this plexus to atria and ventricles by left dorsal, dorsal right atrial, right ventral, and ventral left atrial routes or subplexuses. The right cranial vein receives extrinsic nerves that mainly originate from the right cervicothoracic ganglion and a branch of the right vagus nerve, whereas the left cranial vein is supplied by extrinsic nerves from the left cervicothoracic ganglion and the left vagus nerve. The majority of intrinsic cardiac ganglia are localized on the heart base at the roots of the pulmonary veins. These ganglia are interlinked by interganglionic nerves into the above mentioned nerve plexus of the heart hilum. In general, the examined hearts contained 19 ± 3 ganglia, giving a cumulative ganglion area of 0.4 ± 0.1 mm(2). CONCLUSION: Despite substantial anatomic differences in ganglion number and distribution, the structural organization of the intrinsic ganglionated plexus in the mouse heart corresponds in general to that of other mammalian species, including human.

Atrial tachyarrhythmias and repolarization changes induced by discrete activation of dorsal mediastinal cardiac nerves in canines.

BACKGROUND: Chronotropic "vagal responses" elicited by high-frequency stimulation have been used to identify atrial targets for ablative treatment of atrial tachyarrhythmias (AT), whereas an anatomic approach consisting of extensive ablation of the ganglionated plexus areas has been proposed as an alternative. Therefore, there is a need for precise delineation of juxtacardiac nerves involved in AT initiation and clarification of their regional influences throughout the atria in relation to AT sites of origin, beyond chronotropic effects related to sinus node modulation. METHODS AND RESULTS: Unipolar electrograms were recorded from 191 biatrial epicardial sites in 13 anesthetized canines, with concomitant left atrial endocardial recording from 63 sites in 5 of 13 animals. When electric stimuli were delivered to dorsal mediastinal nerves during the atrial refractory period, atrial premature depolarizations initiating AT were elicited in all animals, most frequently without prior sinus cycle length modification. Among 63 episodes, the sites of origin of early AT beats were localized to (1) the posterolateral left atrial wall in the pulmonary vein region (33%), (2) superior left atrial loci along the Bachmann bundle (55%), and (3) the region of Bachmann bundle insertion into the superior right atrial wall (11%). Moreover, the AT sites of origin were spatially concordant with regional waveform changes during the repolarization phase of unipolar recordings. AT induction and repolarization changes were abolished after atropine administration. CONCLUSIONS: Activation of individual dorsal mediastinal nerves induces AT arising from distinct sites of origin which are spatially concordant with regional atrial repolarization changes.

[Mediastinal neurinoma originating from the intrathoracic vagal nerve: report of a case].

A 37-year-old male consulted our hospital because of an abnormal shadow pointed out on a chest X-ray film during a medical check-up. Computed tomography (CT) and magnetic imaging resonance (MRI) showed that the tumor was located in the mediastinum in contact with the aorta and pulmonary artery. Under the diagnosis of benign mediastinal tumor, video-assisted thoracic surgery was performed. The tumor was about 6 cm in diameter and originated from the left vagal nerve. The vagal nerve was partially involved and had to be resected. He experienced no post-operative complications, and was discharged on the 11th postoperative day. Whether or not to resect the vagal nerve is the most important issue, and hoarseness is the most common complication even in distal cases. It is suggestive that a vagal nerve resection is appropriate in a distal side of the recurrent nerve because post-operative complications are not so severe and local recurrence must be prevented. Recurrent nerve palsy must be cared even in cases of distal resection

Spinal cord stimulation as a novel approach to the treatment of refractory neuropathic mediastinal pain.

Spinal cord stimulation (SCS) offers new hope for patients with neuropathic pain. SCS "neuromodulates" the transmission and response to "painful" stimuli. The efficacy of SCS has been established in the treatment of a variety of neuropathic pain conditions and more recently in refractory angina pectoris, peripheral vascular disease, and failed back surgery syndrome. Recent publications suggest that visceral pain could be successfully treated with SCS. We report the first successful use of a spinal cord stimulator in the treatment of refractory neuropathic mediastinal, esophageal, and anterior neck pain following esophagogastrectomy.

[Schwannoma originating from a mediastinal vagal nerve resected by video-assisted thoracic surgery: a case report].

A 63-year-old man was referred to our hospital due to an abnormal shadow found on a chest CT scan. The CT scan showed a cystic tumor with a central high density in the right upper mediastinal area. The preoperative diagnosis was teratoma in the right upper mediastinal area. Video-assisted thoracic surgery was performed. The tumor was about 3cm in size and originated from the right vagal nerve. Microscopic findings of the resected specimen showed loose growth of spindle cells, in which a myxomatous framework was observed in the peripheral area as well as extended vessels, with thrombis, Verocay bodies, and a nuclear palisading pattern confirmed in the central area. The histological diagnosis was schwannoma originating from the mediastinal vagal nerve. This case was thought to be rare and difficult to diagnose by preoperative imaging findings. Postoperative hoarseness due to dysfunction of the right recurrent nerve occurred. Careful consideration should be given to the indication of video-assisted thoracic surgery for neurogenic mediastinal tumors since postoperative dysfunction may occur.

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs.

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Comparative effects of valsartan and enalapril on cardiac sympathetic nerve activity and plasma brain natriuretic peptide in patients with congestive heart failure.

OBJECTIVE: To evaluate the effects of valsartan on cardiac sympathetic nerve activity, plasma brain natriuretic peptide (BNP) concentration, cardiac function, and symptoms in patients with congestive heart failure (CHF) by comparison with those of enalapril. METHODS: 50 patients with CHF (left ventricular ejection fraction (LVEF) < 40%) were randomly assigned to valsartan (80 mg/day; n = 25) or enalapril (5 mg/day; n = 25). All patients were also treated with a loop diuretic. The delayed heart to mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate were determined from (123)I-meta-iodobenzylguanidine (MIBG) images. Plasma BNP concentrations were measured before and after six months of treatment. The left ventricular end diastolic volume (LVEDV) and LVEF were also determined by echocardiography. RESULTS: In patients receiving valsartan, TDS decreased from a mean (SD) of 43 (8) to 39 (10) (p < 0.01), H/M ratio increased from 1.70 (0.17) to 1.78 (0.22) (p < 0.05), washout rate decreased from 46 (11)% to 41 (10)% (p < 0.05), and plasma BNP concentration decreased from 237 (180) pg/ml to 143 (93) pg/ml (p < 0.05). In addition, LVEDV decreased from 172 (42) ml to 151 (45) ml (p < 0.05) and LVEF increased from 31 (7)% to 39 (10)% (p < 0.001). However, these parameters did not change significantly in patients receiving enalapril. CONCLUSION: Plasma BNP concentration and (123)I-MIBG scintigraphic and echocardiographic parameters improved significantly after six months of treatment with valsartan. These findings indicate that valsartan can improve cardiac sympathetic nerve activity and left ventricular performance in patients with CHF.

Neurilemoma originating from the left recurrent nerve in the superior mediastinum: report of a case.

We report a rare case of neurilemoma originating from the left recurrent nerve in the superior mediastinum.

The distribution of presumptive thoracic paraganglionic tissue in the common marmoset (Callithrix jacchus).

The aortic-pulmonary regions (APR) of seven adult marmosets (Callithrix jacchus) and the region of the right subclavian artery of a further three marmosets were diffusion-fixed with 10% buffered formol-saline solution. In both regions serial 5 microm sections were cut and stained by the Martius yellow, brilliant crystal scarlet and soluble blue method. Presumptive thoracic paraganglionic (PTP) tissue was only observed in the APR. PTP tissue was composed of small groups of cells that varied in size and number. The distribution of the groups of cells was extremely variable, so much so that it would be misleading to attempt to classify their position; they were not circumscribed by a connective tissue capsule, but were always related to the thoracic branches of the left vagus nerve. The cells lay in loose areolar tissue characteristic of this part of the mediastinum and received their blood supply from small adjacent connective tissue arterioles. Unlike the paraganglionic tissue found in the carotid body the cells in the thorax did not appear to have a profuse capillary blood supply. There was, however, a close cellular-neural relationship. The cells, 10-15 microm in diameter, were oval or rounded in appearance and possessed a central nucleus and clear cytoplasm. No evidence was found that these cells possessed a 'companion' cell reminiscent of the arrangement of type 1 and type 2 cells in the carotid body. In conclusion, we found evidence of presumed paraganglionic tissue in the APR of the marmoset which, however, did not show the characteristic histological features of the aortic body chemoreceptors that have been described in some non-primate mammals. A survey of the mediastina of other non-human primates is required to establish whether this finding is atypical for these animals.

Three-field dissection for squamous cell carcinoma in the thoracic esophagus.

An esophageal cancer has frequent metastasis in the cervical and upper mediastinal lymph nodes, in particular along the recurrent nerves. Cervicothoracoabdominal three-field dissection is the most radical and rational lymphadenectomy procedure based on this evidence. During three-field dissection, the nodes along the recurrent nerves from the neck to the mediastinum are more meticulously resected than during any other procedure of radical lymphadenectomy. A consensus has been obtained that complete resection of the recurrent nerve nodes improves the survival rates of patients with cancer in each of the various locations of the thoracic esophagus, and that resection of the supraclavicular and internal jugular nodes improves the survival rates of patients with cancer in the upper thoracic esophagus. There is, however, still some controversies over whether or not resection of the supraclavicular and internal jugular nodes improves the survival rates of patients with cancer in the middle or lower thoracic esophagus. Moreover, there remains many controversies over the indication for three-field dissection regarding metastasis-positivity in the lymph nodes, the numbers of the metastasis-positive nodes, the stage, surgical risks and other aspects. Large randomized prospective studies are needed to accumulate conclusive evidence for the benefits of three-field dissection.

[Intrathoracic neurofibroma originating in the left vagus nerve].

A 20-year-old man was admitted because of an abnormal mass shadow on chest X-ray film. Computed tomography (CT) and magnetic resonance imaging (MRI) disclosed a mass lesion in the superior portion of the left mediastinum. CT scans showed a well-defined mass with low density. Axial MRI rendered the mass lesion with intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. The preoperative diagnosis was bronchogenic cyst. Video-assisted thoracic surgery revealed that the tumor originated in the truncus of the left vagus nerve. The resected tumor was 90 x 24 x 18 mm in size. The postoperative course was uneventful and hoarseness did not develop. The pathologic diagnosis was benign mediastinal neurofibroma without von Recklinghausen's disease. Such cases are extremely rare in the Japanese literature.

Thoracic vagus section distal to the recurrent laryngeal nerve reduces substance. P-immunoreactive innervation in the rat bronchial tree.

The vagal nerve trunk in the mediastinum of mammals divides into two main branches, the thoracic vagus nerve and the recurrent laryngeal nerve, in which the sensory nerve axons are largely involved in neurogenic inflammation in the tracheobronchial airways. A previous study demonstrated that cutting the right-side thoracic vagus nerve but not the recurrent laryngeal nerve inhibited capsaicin-induced neurogenic inflammation in the right bronchial tree of the rat. The effect of left thoracic vagus nerve section is still not known. The main purpose of the present study was to investigate the effect of sectioning the right or left thoracic vagus nerve on the innervation density of substance P-immunoreactive axons in bilateral bronchial trees. Following nerve degeneration, the whole mounts of airway tissues were processed with substance P immunohistochemistry. Denervation of either thoracic vagus nerve reduced the innervation density of axons by 38-71% in different parts of the ipsilateral bronchial tree. The effect of right recurrent laryngeal nerve section was less specific; the innervation density was reduced by 21-39% in the trachea and bronchi of both sides. Capsaicin-induced neurogenic plasma leakage was decreased in the left mainstem bronchus and lobar bronchi after left thoracic vagus nerve section. It is concluded that the thoracic vagus nerve largely contributed to the sensory innervation in the ipsilateral bronchial airways and modulated their functions.

Mediastinal epithelioid hemangioendothelioma in a patient with type IV Ehlers-Danlos syndrome: a case report and review of the literature.

Ehlers-Danlos syndrome (EDS) is a collection of inherited connective tissue disorders with at least 10 types, differentiated on clinical and genetic grounds. Malignancy has been described only rarely in association with the syndrome. Epithelioid hemangioendothelioma (EH) is a rare endothelial tumor, which displays clinical behavior intermediate between that of hemangioma and angiosarcoma. A case report of a 50-year-old man with type IV EDS who was extensively investigated for several years for multiple mediastinal nerve palsies and chest pain. Magnetic resonance imaging (MRI) demonstrated an anterior mediastinal mass, which at biopsy showed EH. Subsequent metastatic spread to liver and lungs is unique among reported cases of mediastinal EH. The patient experienced significant symptomatic improvement from external beam radiotherapy (RT) to the mediastinum. After metastatic disease developed, multiagent chemotherapy was administered, but without response. The literature is reviewed regarding treatment of EH and the potential problems associated with EDS. Although there appears to be no etiological association between EDS and EH, the connective tissue disease clearly contributed to a delay in diagnosis and raised concerns regarding RT tolerance. The potential predisposition to aggressive tumor invasion remains a possibility. In addition, mediastinal EH has the potential to metastasize, and in this case demonstrated resistance to a broad range of chemotherapy agents.

Gross and microscopic anatomy of the human intrinsic cardiac nervous system.

BACKGROUND: The extent and locations of intrinsic cardiac ganglia on the human heart were investigated to facilitate studying their function. METHODS: The locations and number of major intrinsic cardiac ganglia were determined in six human hearts by means of microdissection following methylene blue staining. Light and electron microscopic analyses were performed on right atrial and cranial medial ventricular ganglia obtained from 12 other human hearts. RESULTS: Gross anatomy: Collections of ganglia associated with nerves, i.e., ganglionated plexuses, were observed consistently in five atrial and five ventricular regions. Occasional ganglia were located in other atrial and ventricular regions. Atrial ganglionated plexuses were identified on 1) the superior surface of the right atrium, 2) the superior surface of the left atrium, 3) the posterior surface of the right atrium, 4) the posterior medial surface of the left atrium (the latter two fuse medially where they extend anteriorly into the interatrial septum), and 5) the inferior and lateral aspect of the posterior left atrium. Ventricular ganglionated plexuses were located in fat 1) surrounding the aortic root, 2) at the origins of the right and left coronary arteries (the latter extending to the origins of the left anterior descending and circumflex coronary arteries), 3) at the origin of the posterior descending coronary artery, 4) adjacent to the origin of the right acute marginal coronary artery, and 5) at the origin of the left obtuse marginal coronary artery. Microscopic anatomy: Ganglia ranged in size from those containing a few neurons to large ganglia measuring up to 0.5 x 1 mm. The human heart is estimated to contain more than 14,000 neurons. Neuronal somata varied in size and shape. Many axon terminals in intrinsic cardiac ganglia contained large numbers of small, clear, round vesicles that formed asymmetrical axodendritic synapses, whereas a few axons contained large, dense-cored vesicles. CONCLUSIONS: The human intrinsic cardiac nervous system is distributed more extensively than was considered previously, most of its ganglia being located on the posterior surfaces of the atria and superior aspect of the ventricles. Each ganglion therein contains a variety of neurons that are associated with complex synaptology.

[The monoaminergic innervation of the mediastinal pleura in human fetuses]. / Monoaminergicheskaia innervatsiia mediastinal'noi plevry plodov cheloveka.

Mediastinal pleura was studied in pregnancy second part abortive human fetuses using histological and histochemical technique. It was found to have a well-developed monoaminergic apparatus that includes adrenergic axons and mast cells. Electron microscope study confirmed monoaminergic and single peptidergic vesicles presence in axons. Luminescent method revealed that mast cells of nerve plexuses and blood vessels contain catecholamines and indolalkylamines. Monoaminergic axons and mast cells were shown to constitute a functionally integrative apparatus that regulates local hemodynamics and trophics.