Vagal Trunk Research Articles

THE PROTECTIVE EFFECT OF THE CHOLINERGIC ANTI-INFLAMMATORY PATHWAY AGAINST SEPTIC SHOCK IN RATS

To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-alpha level, and the nuclear factor-kappaB (NF-kappaB) activation during septic shock, male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty-eight rats were randomly assigned into six equal groups: sham CLP group; CLP group; VGX group was subjected to bilateral cervical vagotomy after CLP; STM group was subjected to bilateral cervical vagotomy after CLP plus the left vagus nerve trunk electrical stimulation; THA group was administered tetrahydroaminoacridine after CLP and bilateral cervical vagotomy; and alpha-BGT group was administered alpha-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-alpha level was measured using enzyme-linked immunosorbent assays. The hepatic NF-kappaB activation was determined by Western blotting. Cecal ligation and puncture produced progressive hypotension. Serum aspartate transaminase and alanine transaminase levels significantly increased after CLP challenge. The plasma TNF-alpha level and the hepatic NF-kappaB activation significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated group. Application of constant voltage pulses to the caudal vagus trunk significantly prevented the development of CLP-induced hypotension, alleviated the hepatic damage, and reduced the plasma TNF-alpha production, but electrical stimulation had no effect on the hepatic NF-kappaB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-alpha response; in addition, it had no effect on the hepatic NF-kappaB activation. alpha-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the hepatic NF-kappaB activation. Our results showed that the cholinergic anti-inflammatory pathway might produce a potential protective effect on polymicrobial sepsis in rats.

Conduction between left superior pulmonary vein and left atria and atria fibrillation under cervical vagal trunk stimulation.

Objective: The effect of cervical vagal trunk stimulation on conduction between left superior pulmonary vein and left atria and atria fibrillation have not been systematically studied. We attempted to investigate the electrical conduction between LA and LSPV in dogs with cervical vagal trunk stimulation and evaluate the possible underline substrates for local reentry and initiation and maintenance of AF. Methods: 12 mongrel dogs (18-25 kg) underwent cervical vagal trunk stimulation at high-frequency (60 ms, 1-4V) to produce sinus arrest lasting >2 seconds,complete atrioventricular AV blocking or the sinus rate decreasing more than 50%. Left lateral thoracotomy was performed and the heart was exposed in a pericardial cradle. The HRA, LAA, PV-LAJ, LSPVm and LSPVd was locally stimulated (100 ms, 2-8V). ERP of HRA, LAA, PV-LAJ and within LSPV, ERP heterogeneity within LSPV and conduction between left superior pulmonary vein and left atria and atrial fibrillation inducing rate with vagal response was analyzed. Results: 1. During cervical vagal stimulation, the heart rate was reduced significantly from baseline 156±34 bpm to 75±34 bpm (p< 0.05, n=12), ERP of HRA, LAA, PV-LAJ, LSPVm and LSPVd sites was shortened locally in all animals, ERP hetero-geneity (COV-ERP ) was increased from baseline 3±3% to 30±13% (on average, p< 0.05; n=12) and inducibility of AF was increased from baseline 49.9% to 70.9% with S1S1stimulation (100 ms, 2-8V) and from baseline 3.7% to 43.5% with S1S2 (5 ms decremented stepwise S1S2 300/200 ms, 2-8V, n=12; 2. LA and PV potentials at LA, PV-LAJ, LSPVm and LSPVd was overlapped during sinus rate and separated remarkably by stimulating at distal part of LSPV (n=9); 3. Unidirectional and bi-directional conduction(n=9), bi-directional decremented conduction (n=6), delayed conduction from LSPVp to LSPVd (n=12) and slow conduction from stimulating signal to local tissue potential (n=9) before onset of AF were recorded by pacing from both LSPV and LA. Conclusion: Our study strongly suggested that fast ectopic beating, abnormal vagal nerve activation as well as remodeling conduction between left superior pulmonary vein and left atria might are the common underline substrates for local reentry and AF initiation and maintenance.

Right-sided vagus nerve stimulation in humans: An effective therapy?

Vagus nerve stimulation (VNS) is an additive treatment option for refractory epilepsy. The electrode is placed on the cervical trunk of the left vagus nerve. In patients who are not suitable for left-sided vagus nerve stimulation (L-VNS) right-sided vagus nerve stimulation (R-VNS) may be as effective. In animal models epilepsy is sufficiently suppressed by R-VNS. In a 16 years old boy suffering from medically refractory psychomotoric seizures with secondary generalisation, L-VNS reduced the frequency of generalized seizures. A deep wound infection required the removal of the system eight weeks later. Cicatrisation did not allow preparation of the left vagus nerve, therefore we implanted R-VNS with sufficient seizure suppression. However, compared to L-VNS, the effect occurred months later and cardiac symptoms were induced by stimulation of the right vagus nerve. R-VNS seems to be an effective and alternative therapy in selected patients responding to L-VNS where a left-sided reimplantation is not possible. Placement and adjustment of the device should be performed under ECG control. Further studies are necessary to compare the efficacy of L-VNS and R-VNS.

Laparoscopic adjustable gastric banding with truncal vagotomy versus laparoscopic adjustable gastric banding alone: interim results of a prospective randomized trial

Background In an attempt to potentiate the effect of laparoscopic gastric banding (LGB) on weight reduction and to reduce the risk of weight regain, we added laparoscopic truncal vagotomy (TV) to adjustable LGB. We report on our early interim results of a prospective 5-year randomized clinical trial comparing patients who underwent LGB plus TV (LGBTV) with a control group who underwent LGB alone. Methods From December 2005 to November 2006, patients were randomly allocated to LGBTV or LGB alone. In the LGBTV group, the anterior and posterior vagus trunks were isolated and resected after preparing and encircling the esophagus at the diaphragmatic crus. In both groups, an 11-cm Lap-Band System was positioned by way of the pars flaccida. Results A total of 50 patients were entered into the study. No mortality resulted, and no conversion to laparotomy was needed. Neither group had any intra- or postoperative complications. The mean weight, body mass index, and percentage of excess weight loss were not significantly different statistically between the 2 groups at 12 or 18 months after surgery ( P = NS). At 6 months of follow-up, band adjustment was not required in 10 (50%) of 20 patients with LGBTV compared with 5 (20%) of 25 patients with LGB alone ( P = .034). At 12 months, 7 (35%) of 20 LGBTV patients and 2 (8%) of 25 LGB patients still did not require band adjustment ( P = .024). Conclusion: The results of our study have shown that adding TV to LGB does not cause specific morbidity or mortality compared with LGB alone. During the first postoperative year, the addition of TV to LGB decreased the number of patients requiring band adjustments.

Vagal Nerve Dissection During Pouch Formation in Laparoscopic Roux-Y-Gastric Bypass for Technical Simplification: Does it Matter?

In Roux-Y gastric bypass surgery pouch formation is the most demanding part of the operation. The vagal nerve is usually tempted to be preserved although results reporting beneficial effects are lacking. Dividing the perigastric tissue including the anterior vagal trunk may technically alleviate gastric pouch formation. We evaluated the clinical outcome in patients with and without vagal nerve dissection in patients after Roux-Y gastric bypass (RY-BP). In this study 40 morbidly obese patients undergoing RY-BP have been included. Patients were divided into two groups according to vagal nerve preservation (Group 1, n = 25) or vagal nerve dissection (Group 2, n = 22). Clinical parameters (weight loss, complications, gastrointestinal symptoms), esophageal endoscopy, and motility data (manometry, pH-metry) and a satiety score were assessed. Serum values of ghrelin and gastrin were measured. All procedures were performed by laparoscopy with a 0% mortality rate. One patient of each groups necessitated redo-laparoscopy (bleeding and a lost drainage). All patients significantly reduced body weight (p < 0.01 compared to preoperative) during a median follow-up of 36.1 months. Two patients of Group 2 showed acid reflux demonstrated by pathologic postoperative DeMeester scores. Esophageal body peristalsis and barium swallows did not reveal statistically significant differences between the two groups. Parameters of satiety assessment did not differ between the two groups as did serum values of gastrin and ghrelin. Pouch formation during RY-BP may be alleviated by simply dissecting the perigastric fatty tissue. In this way the anterior vagal trunk is dissected, however, no influence on clinical, functional and laboratory results occur.

The vagal afferent pathway does not play a major role in the induction of satiety by intestinal fatty acid in rats

Intestinal infusion of long-chain fatty acids (LCFAs) strongly suppresses food intake and gut motility. Vagal afferents and cholecystokinin (CCK) signaling pathway are considered to play important roles in intestinal LCFA-induced satiety. Here, we first investigated the influence of vagus nerve on satiety following intestinal LCFA infusion in rats. Jejunal infusion of linoleic acid (LA) at 200 microL/h for 7 h suppressed food intake and the effect lasted for 24 h. The satiety induced by jejunal LA infusion occurred in a dose dependent manner. In contrast, the anorectic effect induced by octanoic acid, a medium-chain fatty acid, was weaker than that induced by LA. The reduction in food intake induced by jejunal LA infusion was not attenuated in rats treated with vagotomy, the ablation of bilateral subdiaphragmatic vagal trunks. Jejunal LA-induced satiety could also be observed in rats with bilateral midbrain transections, which ablates fibers between the hindbrain and hypothalamus. These findings suggest that the vagus nerve and fibers ascending from the hindbrain to the hypothalamus do not play a major role in intestinal LCFA-induced satiety. Jejunal LA infusion also reduced food intake in CCK-A receptor-deficient OLETF rats, suggesting that CCK signaling pathway is not critical for intestinal LCFA-induced anorexia. In conclusion, this study indicates that the vagus nerve and the CCK signaling pathway do not play major roles in conveying satiety signals induced by intestinal LCFA to the brain in rats.

An Experimental Study on the Site Dependency and Mechanism of Vagal Denervation Following Radiofrequency Catheter Ablation for Supraventricular Arrhythmias Including Atrial Fibrillation

Radiofrequency catheter ablation (RFCA) for supraventricular arrhythmias results in parasympathetic nervous damage. Recently, RFCA around the pulmonary veins (PVs) has become a standardized curative therapy for atrial fibrillation (AF). The aim of the present study was to elucidate the relationship between the degree of vagal denervation and RFCA sites, including the PV areas. In 21 dogs, RFCA was performed at the ostium of the right PV (n = 7), ostium of the left PV (n = 7), and posteroseptal site of the right atrium (n = 7). Electrical stimulation of the cervical vagal trunk (ESCV) was performed and the resultant increase in the P-P interval (PPI) observed on the ECG was measured. The PPI was compared between the different RFCA sites. In another 7 animals, the vagal ganglia located in the fat pads that innervate the sinoatrial (SA) node were also stimulated (ESFP), testing the degree of postganglionic damage. The PPI after RFCA was decreased with right PV RFCA whereas there was no change with left PV RFCA. The ESFP yielded a significantly greater decrease in the PPI than the ESCV. The PPI during ESFP was completely blocked by hexamethonium, injected into the fat pad. The ESCV after the hexa-methonium injection did not result in complete disappearance of the PPI. Thus, right PV RFCA markedly damaged the vagal innervation of the SA node, whereas left PV RFCA produced little damage. The major type of damage was partial postganglionic fiber damage. An alternate vagal pathway external to the fat pads is proposed.

The relationship of paroxysmal atrial fibrillation and regional sympathetic innervations in the atria and pulmonary veins: experiment with dogs

To test the hypothesis that regional sympathetic innervation in the atria and pulmonary veins are correlated with atrial fibrillation (AF). Sixteen adult mongrel dogs underwent thoracotomy under general anesthesia. Bilateral cervical vagal trunks were decentralized. Multipolar catheters were placed into right atrial appendage (RAA), left atrial appendage (LAA), left atrium (LA), left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), right superior pulmonary vein (RSPV), and left inferior pulmonary vein (LIPV). The bilateral sympathovagal trunks were stimulated, S1S1 burst stimulation and S1S2 stimulation procedure were performed on different points of RAA, LAA, LA, LSPV, LIPV, RSPV, and LIPV. The TF thus induced was monitored. After that, the dogs were killed with their hearts and lungs were taken out. Immunocytochemical staining of cardiac nerves was performed using anti-tyrosine hydroxylase (TH) antibodies. The nerve fiber density was counted manually for each case and expressed as the mean number per slice. Two dogs died during the experiment and the whole procedure was completed on 14 dogs. There was no significant difference in the AF induction rate among the most points, however, the AF induction rate of the RIPV was significantly lower than those of the other points (all P < 0.05). The levels of density of TH-positive nerves in the atria and atrial appendages were significantly higher than those in the pulmonary veins (P = 0.02). The density of TH-positive nerves in the dogs with AF was significantly higher than that in the dog without AF (P < 0.05). The innervation of sympathetic nerves in atria and pulmonary veins was highly correlated to the induction of atrial fibrillation (r = 0.83). Regional sympathetic hyperinnervation plays an important role in atrial fibrillation induction.

Clock Gene Expression in the Murine Gastrointestinal Tract: Endogenous Rhythmicity and Effects of a Feeding Regimen

Based on observations that the gastrointestinal tract is subject to various 24-hour rhythmic processes, it is conceivable that some of these rhythms are under circadian clock gene control. We hypothesized that clock genes are present in the gastrointestinal tract and that they are part of a functional molecular clock that coordinates rhythmic physiologic functions. The effects of timed feeding and vagotomy on temporal clock gene expression (clock, bmal1, per1-3, cry1-2) in the gastrointestinal tract and suprachiasmatic nucleus (bmal, per2) of C57BL/6J mice were examined using real-time polymerase chain reaction and Western blotting (BMAL, PER2). Colonic clock gene localization was examined using immunohistochemistry (BMAL, PER1-2). Clock immunoreactivity was observed in the myenteric plexus and epithelial crypt cells. Clock genes were expressed rhythmically throughout the gastrointestinal tract. Timed feeding shifted clock gene expression at the RNA and protein level but did not shift clock gene expression in the central clock. Vagotomy did not alter gastric clock gene expression compared with sham-treated controls. The murine gastrointestinal tract contains functional clock genes, which are molecular core components of the circadian clock. Daytime feeding in nocturnal rodents is a strong synchronizer of gastrointestinal clock genes. This synchronization occurs independently of the central clock. Gastric clock gene expression is not mediated through the vagal nerve. The presence of clock genes in the myenteric plexus and epithelial cells suggests a role for clock genes in circadian coordination of gastrointestinal functions such as motility, cell proliferation, and migration.

Motor and sensory re‐innervation of the lung and heart after re‐anastomosis of the cervical vagus nerve in rats

There is no study in the literature dealing with re-innervation of the cardiopulmonary vagus nerve after its transection followed by re-anastomosis. In the present study, we explored the bronchomotor, heart rate and respiratory responses in rats at 2, 3 and 6 months after re-anastomosis of one cervical vagus trunk. The conduction velocity of A, B and C waves was calculated in the compound vagal action potential. We searched for afferent vagal activities in phase with pulmonary inflation to assess the persistence of pulmonary stretch receptor (PSR) discharge in re-innervated lungs. In each animal, data from the stimulation or recording of one re-anastomosed vagus nerve were compared with those obtained in the contra-lateral intact one. Two and three months after surgery, the conduction velocities of A and B waves decreased, but recovery of conduction velocity was complete at 6 months. By contrast, the conduction velocity of the C wave did not change until 6 months, when it was doubled. The PSR activity was present in 50% of re-anastomosed vagus nerves at 2 and 3 months and in 75% at 6 months. Respiratory inhibition evoked by vagal stimulation was significantly weaker from the re-anastomosed than intact nerve at 2 but not 3 months. Vagal stimulation did not elicit cardiac slowing or bronchoconstriction 6 months after re-anastomosis. Our study demonstrates the capacity of pulmonary vagal sensory neurones to regenerate after axotomy followed by re-anastomosis, and the failure of the vagal efferents to re-innervate both the lungs and heart.

Does troncular vagotomy modify the proliferative gastric lesions induced in rats by duodenogastric reflux&lt;A HREF="#back2"&gt;&lt;/A&gt;?&lt;A HREF="#back2"&gt;&lt;/A&gt;

to investigate if combining VT to DGR through the pylorus can modulate the biological behavior of PL induced by DGR and to verify if TV alone can induce morphologic lesions in the gastric mucosa. 62 male Wistar rats were assigned to four groups: 1 - Control (CT) gastrotomy; 2 - Troncular Vagotomy (TV) plus gastrotomy; 3 - Duodenogastric reflux through the pylorus (R) and 4 - Troncular vagotomy plus DGR (RTV). The animals were killed at the 54 week of the experiment. DGR was obtained by anastomosing a proximal jejunal loop to the anterior gastric wall. TV was performed through isolation and division of the vagal trunks. Gastrotomy consisted of 1 cm incision at the anterior gastric wall. PL were analyzed gross and histologically in the antral mucosa, at the gastrojejunal stoma and at the squamous portion of the gastric mucosa. Groups R and RTV developed exophytic lesions in the antral mucosa (R=90.9%; RTV=100%) and at the gastrojejunal stoma (R=54.54%; RTV=63.63%). Histologically they consisted of proliferative benign lesions, without cellular atypias, diagnosed as adenomatous hyperplasia. Both groups exposed to DGR presented squamous hyperplasia at the squamous portion of the gastric mucosa (R= 54.5%; RTV= 45.4%). TV, alone, did not induce gross or histological alterations in the gastric mucosa. TV did note change the morphologic pattern of the proliferative lesions induced by DGR. DGR induces the development of PL in the pyloric mucosa and at the gastrojejunal stoma. TV does not change the morphologic pattern of the proliferative lesions induced by DGR. TV alone is not able to induce morphologic lesions in the gastric mucosa.

Effect of intracranial hypertension on cerebral hemorrhage induced autonomic nerve imbalance*** ○

Background Cerebral hemorrhage can cause the imbalance of nerve function, whereas its mechanism and main impact factors are still not quite clear. Objective To explore the rules about the changes of intracranial pressure in brainstem hemorrhage and internal capsule hemorrhage, and analyze the role of intracranial hypertension in the changes of nerve function caused by cerebral hemorrhage. Design A self-controlled trial. Setting Department of Physiology, Tianjin Medical University. Materials Sixty-five healthy male Japanese white rabbits with long ears (1.5–1.8 kg) were supplied and fed by the Department of Animal Experiment of Tianjin Medical University. The RM6240B biological signal collecting and processing system was used. Methods The experiments were conducted in the Department of Physiology, Tianjin Medical University from August 2001 to May 2006. ▪ The rabbits were anesthetized, then fixed onto the brain stereotaxic apparatus, and afterwards fenestration on skull and intubation to lateral ventricle were performed. The dynamic changes of intracranial pressure were monitored continuously. Rabbits were infused with autologous arterial blood (0.3 mL) into midbrain corpora quadrigemina inferior colliculus to induce model of acute brainstem hemorrhage; models of internal capsule hemorrhage were established by infusing autologous arterial blood into internal capsule. ▪ The dynamic intracranial pressures under the above conditions were recorded continuously with the RM6240B biological signal collecting and processing system. ▪ An animal model of persistent intracranial hypertension was established by infusion of physiologic saline into lateral ventricle. ▪ The changes of the intensity of autonomic nerve discharge were analyzed, using the biological signal collecting and processing system before and after hemorrhage and under persistent intracranial hypertension. ▪ Ten animal models of internal capsule hemorrhage and 10 of brainstem hemorrhage were selected respectively, then gross pathological samples were cut open, and the accuracy of hemorrhage models was affirmed. Histological sections in hemorrhage point and around this point were prepared for with hematoxylin and eosin staining, and the pathological changes were observed under light microscope. Main outcome measures ▪ Changes of intracranial pressures before and after internal capsule hemorrhage and brainstem hemorrhage; ▪ Changes of the discharge intensity of cervical vagus nerve trunk in animal models of internal capsule hemorrhage, brainstem hemorrhage and persistent intracranial hypertension without hemorrhage; ▪ Accuracy of location of internal capsule hemorrhage and brainstem hemorrhage confirmed by gross pathological samples and sections. Results Totally 65 rabbits were involved in the analysis of results. ▪ Dynamic state of intracranial pressure: Intracranial pressure increased obviously at 45 minutes after internal capsule hemorrhage and brainstem hemorrhage, the intracranial pressures were (1.31±0.30), (1.82±0.45) kPa, which were obviously higher than those before hemorrhage [(1.04±0.18), (1.05±0.19) kPa, P < 0.01]. ▪ Discharge of vagus nerve: Under intracranial hypertension, the discharge of cervical vagus nerve trunk was enhanced, and the discharge intensity of vagus nerve trunk was significantly different before and after persistent intracranial hypertension [(364.28±78.55), (1252.19±151.75) μV·s, P < 0.01]. The discharges of cervical vagus nerve trunk were significantly enhanced after internal capsule hemorrhage and brainstem hemorrhage ( P < 0.01). ▪ Validation of hemorrhage sites: The hemorrhage sites were internal capsule and brainstem on histopathological sections. Conclusion Intracranial pressure may play an important role in the pathophysiological process of vagus nerve imbalance caused by cerebral hemorrhage.

Autonomic Ganglionated Plexi: Characterization and Effect of Epicardial Microwave Ablation in a Canine Model of Vagally Induced Acute Atrial Fibrillation

: Autonomic ganglionated plexi (GP) in fat pads near the pulmonary veins may contribute to initiation and maintenance atrial fibrillation (AF). We attempted to localize these plexi in a canine model, and evaluate the efficacy of microwave ablation in eliminating their vagal reflexes. : 8 Mongrel dogs (25-31 kg), underwent cervical vagal trunk stimulation to produce AV nodal block and sustained AF. Sternotomy was performed and the epicardial fat on the posterior left atrium and pulmonary veins was locally stimulated at high-frequency (20 Hz, 3-5 mA). Locations that produced a vagal response were identified and in 7 dogs ablated using the Flex 4 epicardial microwave ablation probe (Guidant Corp) at 65 watts/90 sec. One animal was a control and not ablated. Vagal responses were retested with local stimulation as well as stimulation of the cervical vagal trunks. The presence of AV block and duration of sustained AF was recorded. : Baseline cervical vagal stimulation produced AV block and AF in all the animals. Local high-frequency stimulation (HFS) elicited vagal responses at the junction of the inferior vena cava and the middle pulmonary vein (IVC-MPV) in 8 animals, the base of the left pulmonary veins/ligament of Marshall (LoM) in 5 animals, and between the upper and lower right pulmonary veins (RPV) in 2 animals. Microwave ablation at the IVC-MPV eliminated the vagal response upon local fat pad HFS. Cervical vagal trunk stimulation yielded less AV block (n = 2) or no AV block (n = 5) after microwave ablation of the IVC-MPV alone (n = 4) or in conjunction with LoM area ablation (n = 3). The average duration of AF during cervical vagal stimulation decreased significantly from baseline (52.7 ± 27.0 sec) versus after fat pad ablation (13.8 ± 20.3 sec, p = 0.004). : In a canine model we found the primary epicardial autonomic ganglionated plexi to be at the junction of the IVC-MPV. Epicardial microwave ablation of this GP eliminated the vagal response during local fat pad stimulation; and attenuated or eliminated AV block and induction of sustained AF during cervical vagal trunk stimulation. Epicardial microwave ablation of the ganglionated plexi in epicardial fat pads is feasible and can eliminate vagal reflexes that maybe important in atrial fibrillation.

Transfecting rat heart with human pacemaker gene in vivo to create a biological pacemaker

To test the ability and safety of injecting the hHCN gene into the ventricle of intact rats to create a novel biological pacemaker and to explore the duration of the hHCN over-expression in vivo. Adenoviral constructs incorporating hHCN4 and green fluorescent protein (GFP) were subepicardially injected into the rats' left ventricular wall in situ (n = 10). Control group was injected with adenoviral constructs of GFP alone (n = 10). ECGs were recorded every day within the initial three days after operation. Up to seven days after injection, all rats were anesthetized and subjected to cervical vagal trunks stimulation to permit the emergence of escape rhythm. Then pace-mapping was performed by the hand-hold electrode. Finally, hearts were removed for histology and immunofluorescence study. Ventricular arrhythmic events were not found during the first three days. During vagal stimulation, the rate of spontaneous rhythm in the hHCN4-injected group was significantly more rapid than that in the control group (69 bpm +/- 6 bpm vs 41 bpm +/- 10 bpm, P < 0.001). Pace-mapping confirmed the escape rhythm in the hHCN4-injected group was originated near the injection site. Immunofluorescence study showed the overexpression of hHCN4 on the site of injection. However, the duration of hHCN overexpression was no more than one month after injection. The overexpression of hHCN4 provides ventricular escape rhythm with the physiologically acceptable rate. Long-term feasibility of this approach needs to be tested.

Vagal integrity in vagal-sparing esophagectomy: a cadaveric study

Esophagectomy is associated with a significant number of complications, some of them related to the concomitant vagotomy. The vagal-sparing esophagectomy is an attractive alternative to the conventional procedure; however, few clinical series have attested the integrity of the vagi nerves after esophagectomy. The surgical anatomy of the vagus in the mediastinum has received little interest as well. The anatomy of the vagus was studied in 30 fresh cadavers. Twenty cadavers were submitted to a vagal-sparing esophagectomy, and after the procedure, anatomical vagal integrity was evaluated. Concerning the anatomy of the vagus, one or more vagal trunks were present in all cases. Four patterns were identified: Type I, two distinct trunks without communicating branches, present in eight (26.7%) cases; Type II, two distinct trunks with communicating branches, present in 17 (56.7%) cases; Type III, one or more bifurcated trunks, present in four (13.3%) cases; and Type IV, crossing trunks, present in one (3.3%) case. Regarding the esophagectomy, operative accidents were not noticed; in five cases, there was incomplete removal of the muscular layer of the esophagus. In all cases vagi nerves were preserved. The vagus is preserved in a cadaveric model of the vagal sparing esophagectomy, irrespective of the anatomy of the vagus in the mediastinum.

Correspondence

We found the most interesting aspect of the article by Oh et al 1 Oh S. Zhang Y. Bibevski S. Marrouche N.F. Natale A. Mazgalev T.N. Vagal denervation and atrial fibrillation inducibility: epicardial fat pad ablation does not have long-term effects. Heart Rhythm. 2006; 3: 701-708 Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar in the June 2006 issue of Heart Rhythm was the restoration of sinus node slowing and AV conduction block by right vagal stimulation 4 weeks after acute denervation of two clusters of ganglionated plexi (GP) on the heart. However, several major problems were evident throughout the article, starting with the article title, “Vagal denervation and atrial fibrillation inducibility: Epicardial fat pad ablation does not have long-term effects.” Previous studies have clearly shown that both parasympathetic and sympathetic elements reside in the GP on the heart 2 Lazzara R. Scherlag B.J. Robinson M.J. Samet P. Selective in situ parasympathetic control of the canine sinoatrial and atrioventricular nodes. Circ Res. 1973; 32: 393-401 Crossref PubMed Scopus (123) Google Scholar , 3 Ardell J.L. Structure and function of mammalian intrinsic cardiac neurons. in: Armour J.A. Ardell J.L. Neurocardiology. Oxford University Press, New York1994: 95-114 Google Scholar , 4 Singh S. Johnson P.I. Javed A. Gray T.S. Lonohyna V.A. Wurster R.D. Monomine and histamine synthesizing enzymes and neurotransmitters within neurons of adult human cardiac ganglia. Circulation. 1999; 99: 411-419 Crossref PubMed Scopus (75) Google Scholar ; therefore, the implication that only vagal denervation was induced is misleading. The authors must recognize that their epicardial fat pad ablation procedure was only partial because they left intact the GPs at the antra of the left superior and left inferior pulmonary veins, as well as other GP found along the posterior left atrium. Furthermore, use of right cervical vagal trunk stimulation may be inappropriate because the form of atrial fibrillation (AF) induced probably is due to macroreentry, which is short-lived (≤1 minute) and not due to sustained focal ectopy arising from pulmonary veins (PVs). 5 Po S.S. Scherlag B.J. Yamanashi W.S. Edwards J. Zhou J. Wu R. Geng N. Lazzara R. Jackman W.M. Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein–atrial junction. Heart Rhythm. 2006; 3: 201-208 Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar The latter has been shown to occur by acetylcholine injection into fat pads containing GP adjacent to a right or left PV. The focal AF induced arises from the PV and sustains for periods longer that 20 minutes. To the Editors—ResponseHeart RhythmVol. 3Issue 10PreviewThe letter by Dr. Scherlag and associates commenting on our article published in Heart Rhythm1 provides a welcome opinion from one of the strong proponents of autonomic neural denervation as a potential novel therapeutic strategy for patients with atrial fibrillation (AF). Full-Text PDF

Netrin/DCC‐mediated attraction of vagal sensory axons to the fetal mouse gut

Vagal sensory axons and migrating neural crest-derived precursor cells follow similar pathways to reach the gut. The crest-derived cells express the netrin receptor deleted in colorectal cancer (DCC) and migrate toward netrins expressed by the intestinal mucosa and pancreas; this attraction is required for the formation of submucosal and pancreatic ganglia. We tested the hypothesis that enteric netrins also attract vagal sensory fibers. These axons were located as a function of age in fetal mice by applying the lipophilic tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) bilaterally to nodose ganglia. DiI-labeled axons were found in the esophagus and proximal stomach by E12 and, more distally, in the small bowel at E14-E16. Transcripts encoding DCC were expressed in the nodose ganglia of mice from E12 to adulthood but were developmentally regulated. Paraesophageal anterior and posterior vagal trunks were DCC immunoreactive from E12 to E16. Transcripts encoding netrin-1 were expressed in the developing foregut and midgut; netrin-1 immunoreactivity was detected in the outer gut mesenchyme and mucosal epithelium. Neurites from explanted E14 nodose ganglia grew selectively toward cocultured E14 distal foregut explants (P < 0.01). Antibodies to DCC specifically abolished this preferential outgrowth (P < 0.05). Nodose axons also grew selectively toward cocultured netrin-secreting 293-EBNA cells (P < 0.005); antibodies to DCC again blocked this preferential outgrowth (P < 0.05). These data suggest that netrins, which are expressed in the bowel, attract DCC-expressing vagal sensory axons.

The Vagus Nerve: A Tonic Inhibitory Influence Associated With Inflammatory Bowel Disease in a Murine Model

The recently proposed Inflammatory Reflex describes an interaction between the vagus nerve and peripheral macrophages, resulting in attenuation of proinflammatory cytokine release in response to systemic exposure to bacterial endotoxin. The purpose of this study was to determine whether a similar vagus/macrophage axis modulates the inflammatory responses in the colon in mice. We assessed the Disease Activity Index (DAI), macroscopic and histologic damage, serum amyloid-P level, and myeloperoxidase activity in colitis induced by administration of dextran sodium sulfate (DSS) in healthy and vagotomized C57BL/6 and in mice deficient in macrophage-colony stimulating factor (M-CSF)-induced and in hapten-induced colitis. A pyloroplasty was performed in vagotomized mice. DAI, macroscopic and histologic scores, myeloperoxidase activity, levels of serum amyloid-P, and colonic tissue levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were increased significantly in vagotomized mice 5 days post-DSS and 3 days after hapten-induced colitis compared with sham-operated mice that received DSS or the hapten. Pretreatment with nicotine significantly decreased each of these markers in vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham-operated DSS-treated mice. Conversely, hexamethonium treatment significantly increased each of these markers in the sham-operated DSS-treated mice. Vagotomy had no effect on the colitis in M-CSF-deficient mice. The vagus nerve plays a counterinflammatory role in acute colitis via a macrophage-dependent mechanism, involving hexamethonium-sensitive nicotinic receptors. The identification of a counterinflammatory neural pathway would open new therapeutic avenues for treating acute exacerbations of inflammatory bowel disease.

Pancreatic vasoconstrictor responses are regulated by neurons in the rostral ventrolateral medulla

The pancreas receives sympathetic input which arises from several premotor cell groups in the CNS including the rostral ventrolateral medulla (RVLM). In this study, we examined the influence of electrical stimulation of the RVLM on pancreatic blood flow measured by laser Doppler flowmetry and gastric blood flow measured by ultrasonic Doppler flowmetry in halothane-anesthetized rats. The laser Doppler flow measurement technique was validated by demonstration that pancreatic conductance was reduced by systemic administration of the vasoconstrictor phenylephrine and increased by the vasodilator sodium nitroprusside. Sympathetic vasomotor withdrawal induced by either administration of phenylbiguanide (2 and 10 μg/kg, i.v.) or electrical stimulation of the central end of the cervical vagal trunk (5 Hz, 2 ms, 50–150 μA) produced depressor responses and increases in pancreatic and gastric vascular conductance. Electrical stimulation of the RVLM (50 Hz, 0.5 ms, 25–75 μA) produced pressor and tachycardic responses accompanied by decreases in pancreatic and gastric vascular conductance. All responses to RVLM stimulation were abolished by blockade of ganglionic neurotransmission (hexamethonium bromide, 20 mg/kg, i.v.). These data suggest that RVLM presympathetic vasomotor neurons are a primary source of tonic sympathetic vasomotor drive to the pancreatic and gastric vasculature.

V8: Laparoscopic management of perforated marginal ulcer after laparoscopic Roux en Y gastric bypass

Case presentation of a 53 year old female who presented with an acute abdomen 15 months after laparoscopic Roux en Y gastric bypass for morbid obesity. The patient had been treated by primary care manager for anastomotic marginal ulcer with proton pump inhibitors. An abdominal CT scan demonstrated intraperitoneal air in the area of the lesser omentum and above the liver without abscess. Video demonstrates mobilization of the remnant stomach and duodenum for possible sites of perforation. Dissection of the Roux limb and anastomotic junction is presented with simultaneous endoscopy. Identification of a posterior perforation in the area of chronic inflammation is confirmed endoscopically as well as laparoscopically. Oversewing of the perforation with jejunal and omental patching is performed. Next, dissection at the hiatus is initiated to localize and isolate the vagal trunks. Truncal vagotomy with hiatal closure is documented. Postoperative upper gastrointestinal series images are illustrated.