Influence Of Vagotomy Research Articles

Unilateral Vagotomy Blunts Cardiorespiratory Responses to Vagal Afferent Stimulation and Nucleus Tractus Solitarii (NTS) Glutamate Microinjection

The nTS of the brainstem is the initial integration site of sensory information from the cardiorespiratory system, including afferents from the vagus nerve carrying input from the heart and lungs. The nTS is an important site of neuroplasticity, which depends on factors including neuronal and astrocytic activity, with the latter regulating glutamate (Glu) signaling. We have shown that unilateral transection of the vagus nerve to decrease afferent input results in morphologic changes in nTS glia. Vagal nerve transection also decreases nTS synaptic transmission studied in vitro. The influence of vagotomy on in vivo cardiorespiratory function via afferent‐driven Glu signaling is unknown. We hypothesized that chronic vagotomy blunts cardiorespiratory responses to vagal afferent stimulation via decreased Glu signaling. Male Sprague‐Dawley rats (6‐wk, N=19) were randomly assigned to vagotomy or sham groups. Right cervical vagus nerve transection caudal to the nodose ganglion or sham surgery was performed. One week after surgery, rats were anesthetized, ventilated, and instrumented to measure mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Intact vagus nerves were transected acutely to prevent efferent stimulation. Left and right vagus nerves were stimulated (20 sec, 0.2mA, 2‐10Hz, 0.5ms pulse width) and responses recorded for 3 minutes. Chronic vagotomy had no effect on baseline cardiorespiratory parameters compared to shams. Vagal nerve stimulation on either side increased MAP, HR, and SSNA and decreased PhrNA in all groups. There were no consistent group differences in MAP, HR, and SSNA responses. However, chronic vagotomy blunted the stimulation‐induced decrease in PhrNA frequency and amplitude and decreased apnea duration on the ipsilateral side compared to contralateral stimulation and to shams. To evaluate the mechanism of altered respiratory responses, Glu was nanoinjected (30nL, 1‐10mM) into the left and right nTS of chronic vagotomy and sham rats. Glu decreased MAP, HR, SSNA, and PhrNA in all groups and on both sides. Chronic vagotomy had minimal effects on MAP and SSNA responses, but blunted the decrease in HR and PhrNA frequency and amplitude during ipsilateral Glu injection compared to contralateral. The blunted responses to vagal afferent stimulation and nTS glutamate suggest that chronic vagotomy alters Glu signaling in part via postsynaptic mechanisms. Additional experiments are needed to determine the mechanisms (including the role of astrocytes) of altered nTS Glu signaling to changes in afferent input in cardiorespiratory health and disease.

Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats.

SummaryThe autonomic nervous system (ANS) conveys neuronal input from the brain to the stomach. We investigated mechanisms through which urocortin 1 (UCN1) injected intracerebroventricularly (ICV, 300 pmol/rat) inhibits circulating ghrelin in rats. This was achieved by assessing (1) the induction of c-fos gene expression as a marker of neuronal activation in specific hypothalamic and caudal brainstem regulating ANS; (2) the influence of vagotomy and pharmacological blockade of central and peripheral α- and β-adrenergic receptor (AR) on ICV UCN1 -induced reduction of plasma ghrelin levels (determined by ELISA); and (3) the relevance of this pathway in the feeding response to a fast in rats. UCN1 increased c-fos mRNA expression in key brain sites influencing sympathetic activity namely the hypothalamic paraventricular and ventromedial nuclei, locus coeruleus, nucleus of the solitary tract, and rostral ventrolateral medulla, by 16-, 29-, 6-, 37-, and 13-fold, respectively. In contrast, the dorsal motor nucleus of the vagus had little c-fos mRNA expression and ICV UCN1 induced a similar reduction in acylated ghrelin in the sham-operated (31%) and vagotomized (41%) rats. An intraperitoneal (IP) injection of either a non-selective α- or selective α2-AR antagonist reduced, while a selective α2-AR agonist enhanced ICV UCN1-induced suppression of plasma acylated ghrelin levels. In addition, IP injection of a non-selective β- or selective β1-AR agonist blocked, and selective β1-AR antagonist augmented, the ghrelin response to ICV UCN1. The IP injections of a selective α1- or non-selective β or β2-AR antagonists, or any of the pretreatments given ICV had no effect. ICV UCN1 reduced the 2-h food intake in response to a fast by 80%, and this effect was partially prevented by a selective α2-AR antagonist. These data suggest that ICV UCN1 reduces plasma ghrelin mainly through the brain sympathetic component of the ANS and peripheral AR specifically α2-AR activation and inactivation of β1-AR. The α2-AR pathway contributes to the associated reduction in food intake.

Clinical influence of vagotomy on postoperative acute phase response

Although there is increasing evidence suggesting that the vagus nerve functions as a connector between the nervous and immune systems in animals, little is known about the role of the vagus nerve in postoperative acute phase response in humans. The extent of fever and acute phase protein response and the production of inflammatory cytokine during the early postoperative period were compared among the patients who had undergone total gastrectomy including truncal vagotomy (n = 13), those having distal gastrectomy with division of vagal branches (n = 14), and the patients with vagal nerve preserving gastrectomy (n = 12). There was no significant difference in serum levels of C-reactive protein, alpha-1-antirypsin, and interleukin-6 among the three groups. Also, postoperative maximum body temperature was similar. Vagotomy did not influence acute phase response after gastric cancer surgery. A multipathway mechanism for acute phase response including the induction of fever is suggested.

Proximal jejunal and distal ileal extrinsic innervation in the rabbit and dog.

Abstract The varying patterns of motor behaviour of isolated and interposed jejunal and ileal segments in the rabbit and the dog previously reported (Jenkins and Macleod, 1970) were examined by selective denervation techniques. One hundred and twenty-three paired experiments were conducted on rabbits and 55 similar experiments were performed on dogs. Length-matched paired segments of proximal jejunum and distal ileum were isolated and filled with saline at a constant rate. Segmental resistance to filling was regarded as an index of tone. The influence of vagotomy and of sympathectomy on the tone of the segments was studied in segments supplied by one or by two vessels. Vagotomy caused a decrease in tone in the proximal jejunal segments, while sympathectomy had little effect. In segments of distal ileum sympathectomy resulted in segments behaving in a similar fashion, while vagotomy had an unpredictable effect on tone. The results suggest a uniform distribution of the vagus to the whole length of the small bowel in the rabit and the dog, serving to maintain the tone of the bowel. It is deduced that sympathetic supply to the proximal jejunum isabsent in these animkals and is distributed to the distal ileum only in an irregular fashion. The relevance of these observations to the clinical use of interposed small-bowel segments is considered.

Reabertura do piloro gastroduodenal após sua cerclagem, em ratos

OBJETIVOS: A lesão duodenal é um evento pouco freqüente, que incide em 3% a 12% dos pacientes com trauma de abdome. A sutura dessa ferida e a drenagem adequada da região é o tratamento mais utilizado nas lesões menores. Entretanto, as feridas de maior dimensão continuam sendo um desafio para a escolha do melhor tratamento. O fechamento do piloro e o desvio do trânsito digestório por meio de anastomose gastrojejunal é a conduta mais freqüente nessas situações. Os objetivos deste estudo foram verificar se há diferença entre o tempo de reabertura pilórica após sua oclusão com diferentes fios e se a vagotomia influencia nas alterações tissulares locais. MÉTODO: Foram estudados 30 ratos, submetidos à cerclagem do piloro gastroduodenal e derivação gastrojejunal. Os animais foram divididos em três grupos (n = 10), de acordo com o tipo de fio utilizado no fechamento pilórico: categute simples, ácido poliglicólico e polipropileno. Metade dos animais de cada grupo (n = 5) foram também submetidos a vagotomia troncular. O estudo pós-operatório consistiu de radiografia abdominal após injeção intragástrica de contraste baritado, semanalmente até a constatação de trânsito gastroduodenal. Em seguida, as regiões pilórica e da anastomose gastrojejunal foram retiradas para análise histológica. A comparação entre os grupos foi feita pelo teste de Kaplan-Meier. RESULTADOS: O fio de polipropileno manteve o piloro fechado por mais tempo (36,3 ± 11,6 dias) em relação aos demais fios (p <0,05), não havendo diferença entre os fios de ácido poliglicólico (25,8 ± 14,2 dias) e categute simples (18,7 ± 10,2 dias). A vagotomia não influenciou no tempo de reabertura pilórica, mas acompanhou-se de menor reação inflamatória gástrica. CONCLUSÕES: O fio inabsorvível foi o mais adequado para a exclusão do trânsito pilórico e a vagotomia não influenciou no tempo de reabertura pilórica, mas reduziu a intensidade da gastrite pós-operatória.

4. A technique to simultaneously quantify gastric and biliary function: Application of the technique to the investigation of the influence of vagotomy on gall bladder function after fundoplication

4. A technique to simultaneously quantify gastric and biliary function: Application of the technique to the investigation of the influence of vagotomy on gall bladder function after fundoplication

Influence of vagotomy on the baroreflex sensitivity in anesthetized dogs with experimental heart failure

In a previous study (Wang, W., J. S. Chen, and I. H. Zucker. Circ. Res. 68: 1294-1301, 1991), we showed a depression in baroreflex gain in dogs with pacing-induced heart failure. This depression was not accompanied by a decrease in the central gain (carotid sinus nerve stimulation vs. renal nerve activity). These previous experiments were carried out on animals that were vagotomized and aortic denervated. In the present study these experiments were repeated, and the data were analyzed both in the intact and vagotomized state. Dogs were cardiac paced at 250 beats/min until heart failure was noted. Sham dogs were used as controls. The carotid sinuses were isolated, and the aortic nerves were sectioned. Activity from a renal sympathetic nerve (RSNA) was recorded with arterial pressure and carotid sinus pressure (CSP) during bilateral step increases in CSP from 25 to 300 mmHg. Mean arterial pressure (MAP) and RSNA responses to carotid sinus pressurization and to carotid sinus nerve stimulation were tested before and after bilateral vagotomy, and curves describing these relationships were constructed. Before vagotomy, the peak response relating stimulation frequency to MAP was significantly depressed in dogs with heart failure (-18.3 +/- 4.7 vs. -37.0 +/- 2.2%, P < 0.001). In addition, the CSP-MAP curves were depressed in dogs with heart failure. Frequency-RSNA curves were not altered in heart failure. There were no significant changes in the baroreflex gain responses to pressurization or electrical stimulation after vagotomy in either sham or heart failure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of vagotomy on bicarbonate secretion in the rat proximal duodenum.

The influence of vagotomy on bicarbonate secretion in the proximal duodenum was assessed in rats receiving truncal, hepatoduodenal and gastric vagotomy. Two weeks after vagotomy, animals fasted for 24 hr were subjected to laparotomy under urethane anesthesia. A proximal duodenal loop excluding the outlet of the common bile duct was prepared as part of an airtight extracorporeal perfusion circuit. The circuit was filled with a bathing solution at pH 4.5 and which was perfused at a rate of 10 ml/min at a constant temperature of 37 degrees C. The pH and CO2 tension of the bathing solution were determined using microelectrodes, and bicarbonate secretion was calculated from the pH and CO2 tension data by the Henderson-Hasselbalch equation. The bicarbonate secretion at the first portion of the duodenum over a 60-min period was significantly higher in the truncal and hepatoduodenal vagotomy groups than in the control group. However, there was no significant difference between the gastric vagotomy and control groups. Furthermore, no significant difference was noted between the truncal and hepatoduodenal vagotomy groups. Since bicarbonate secretion was increased by hepatoduodenal vagotomy, the hepatoduodenal branch of the vagus nerve appeared to inhibit bicarbonate secretion at the first portion of the duodenum.

Influence of vagotomy on plasma ANP level increases elicited by veratrine infusion and atrial distension in the dog

Influence of vagotomy on plasma ANP level increases elicited by veratrine infusion and atrial distension in the dog

Vitamin D Deficiency after Highly Selective Vagotomy

While bone disease is occasionally seen after gastrectomy, the influence of vagotomy on calcium and vitamin D metabolism is uncertain. We have, therefore, investigated 23 male patients who had undergone highly selective vagotomy for ulcer 4.3 +/- 1.2 years previously. The 25OHD concentrations were decreased (p less than 0.05), the 1,25(OH)2D concentrations elevated (p less than 0.05) and the immunoreactive parathyroid hormone concentrations normal. Local and total bone mass were normal compared to age-matched men, and there was no biochemical evidence of increased bone turnover. We suggest that the changes in calcium absorption, which are described in the literature after vagotomy, are mediated by 1,25(OH)2D. Although the changes in vitamin D metabolism do not lead to calcium-metabolic disturbances in selected patients, we believe that some will eventually develop vitamin D deficiency and that vitamin D supplementation should be considered.

Influence of vagotomy and of atropine on the anti-shock effect of adrenocorticotropin

ACTH-(1–24), intravenously injected at the dose of 160 ug/kg to rats bled to the point of otherwise irreversible hypovolemic shock, causes a prompt and sustained increase in blood pressure and pulse amplitude, all treated rats surviving at the end of the experiment (2 hr). Bilateral vagotomy, as well as atropine sulphate (2 mg/kg i.p. immediately before bleeding), almost completely abolishes the anti-shock activity of ACTH. These data indicate that a central cholinergic pathway and vagal afferent (but not efferent) fibers play an important role in the anti-shock effect of ACTH.

Influence of vagotomy in domestic fowls on feeding activity, food passage, digestibility and satiety effects of two peptides

The effects of bilateral vagotomy at the level of the proventriculus, in immature female fowls (VAG), on body weight, feeding activity parameters, rate of food passage, digestibility, and satiety effects of bombesin (BBS) and cholecystokinin octapeptide (CCK8), were compared with those in sham-operated controls (SHAM). SHAM birds gained weight at a greater rate postoperatively than before their operation, whereas VAG birds did not. Daily food intake did not change significantly as a result of the operation with either SHAM or VAG birds, and the only effect on feeding activity parameters was on the length of intermeal intervals, which increased in VAG birds. Rate of passage of the layers' mash diet was slower, and its apparent digestibility lower, in VAG than in SHAM birds. Short-term suppression of food intake, following intravenous injections of BBS (10 μg/kg) or CCK8 (10 μg/kg), did not differ between SHAM and VAG birds. The different postoperative weight gains may have been a consequence of different weights of food digested, and the difference in interval length was probably due to the different rates of food passage. The results of these experiments indicate that efferent information affecting rate of passage and digestibility travels via the vagus, but that afferent information concerned with initiation and termination of meals, and with satiety effects of BBS and CCK8, does not. Instead, such afferent information may travel via the intestinal nerve, which is unique to birds.

Influence of vagotomy on mucosal protection against alcohol-induced gastric damage in the rat

We examined the role of the vagus nerve in mediating the protective effects of subcutaneous 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) or of the mild irritant 30% ethanol (topically) against gastric mucosal injury induced by concentrated solutions of ethanol. Anesthetized rats underwent either truncal vagotomy or sham truncal vagotomy and were studied acutely or 7 days later. Under acute conditions, in rats with intact vagi, oral saline followed by 100% ethanol produced severe gastric hemorrhagic and necrotic lesions throughout the glandular gastric mucosa. Oral 30% ethanol or pretreatment with 16,16-dmPGE2 (5, 10, or 25 μg/kg) before giving oral saline significantly reduced the magnitude of injury when mucosa was subsequently exposed to 100% ethanol. In animals with truncal vagotomy, the protective effect of 16,16-dmPGE2 or 30% ethanol was not observed. Similar results were noted when animals were studied 7 days after sham or truncal vagotomy. In other studies, the ability of 16,16-dmPGE2 to prevent gastric injury induced by 50% ethanol or 80 mM aspirin in acid solution (160 mM HCl) with and without prior vagotomy was compared. Although 16,16-dmPGE2 (5 or 25 μg/kg) pretreatment significantly reduced the degree of gastric damage induced by both agents in the nonvagotomized state, and by aspirin under vagotomized conditions, only partial protection by 16,16-dmPGE2 against ethanol injury was observed in the vagotomized state. These results suggest that the mechanisms whereby prostaglandins mediate their protective effects against aspirin and ethanol may be different and that the vagus nerve influences the ability of 16,16-dmPGE2 and of the mild irritant 30% ethanol to prevent alcohol-induced gastric injury in the rat stomach.

Influence of vagotomy upon GIP release in patients with peptic ulcer.

Twenty-two vagotomized peptic ulcer patients were studied on the influence of vagotomy on the release of GIP. Moreover, the relationship between acid output and GIP release was analyzed. These patients underwent one of the three types of operation; truncal vagotomy with pyloroplasty (TV + P) selective vagotomy with pyloroplasty (SV + P) and selective vagotomy with antrectomy (SV + A). Before and after surgery, a gastric juice study and an oral glucose tolerance test were performed on separate days. Maximum acid output in response to tetragastrin correlated significantly with integrated GIP response after oral glucose loading. In the SV + P group, the response of GIP was slightly greater after surgery. In the SV + A group, the integrated GIP response diminished postoperatively, although, after surgery, GIP reached its peak sooner. The integrated GIP response was greater in the SV + P group than in the TV + P group. The response of GIP was less in the SV + A group than in the SV + P group. These changes were insignificant. In conclusion, it is presumed that GIP release is affected by gastric acid, gastric emptying time, intestinal transit time and vagal nerve action.

Influence of vagotomy on changes in feline plasma catecholamine levels induced by occlusion of either the left or right coronary vessel.

The purpose of this study was two-fold: (1) to determine the effect of occlusion of the left anterior descending branch (LAD) of the left coronary artery or the right coronary (RC) artery on plasma catecholamine levels, and (2) to determine whether bilateral vagotomy has an effect on changes in plasma catecholamine levels evoked by coronary occlusion. Chloralose anaesthetised cats subjected to LAD occlusion exhibited increases in plasma noradrenaline and adrenaline at 3 min post-occlusion. The increases in noradrenaline and adrenaline were unrelated to the hypotension that occurred at this time. Bilateral vagotomy did not appear to alter the effect of LAD occlusion on catecholamine release into the circulation but did unmask a significant correlation between the degree of hypotension and the magnitude of increase in plasma catecholamines. Right coronary occlusion in animals with intact and sectioned vagus nerves evoked noradrenaline and adrenaline release that was significantly correlated with a fall in arterial pressure. Bilateral vagotomy per se caused an increase in baseline plasma catecholamine levels. Pretreatment with atropine mimicked the increase in baseline catecholamine levels seen with vagotomy. These results indicate that occlusion of the LAD and RC arteries increase the release of catecholamines into the circulation. The role of the vagus nerves in this response was observed only with LAD occlusion and consisted of altering the relationship between the degree of hypotension and the magnitude of increase in plasma catecholamines. That is, after vagotomy, the decrease in blood pressure following LAD occlusion was effective in causing release of catecholamines, presumably because of the hypotension causing a decrease in baroreceptor stimulation. Finally, it appeared that vagotomy increases the release of noradrenaline into the circulation by removing efferent vagal tone that inhibits noradrenaline release. This inhibitory action is mediated by activation of muscarinic receptors.

Pathogenesis of duodenal ulceration produced by cysteamine or propionitrile: influence of vagotomy, sympathectomy, histamine depletion, H-2 receptor antagonists and hormones.

Insight into the pathogenesis and etiology of experimental duodenal ulceration was sought by studying the modulation of this disease in rats by selective vagotomy, chemical sympathectomy, histamine depletion, histamine H-2 receptor antagonists (eg, metiamide, cimetidine), or endocrine ablations. Gastric secretion was examined in intact and pylorus-ligated animals. The formation of duodenal ulcers induced by the administration of propionitrile or cysteamine was abolished by vagotomy, decreased by sympathectomy, histamine depletion, histamine H-2 receptor antagonists, hypophysectomy, thyroidectomy, or adrenalectomy. Cimetidine and metiamide exerted a dose-dependent antiulcer effect, but metiamide enhanced the mortality of rats given propionitrile or cysteamine. The non-ulcerogen derivative of cysteamine, ethanolamine, did not increase mortality when given in combination with metiamide. The gastric hyperacidity elicited by cysteamine was reduced by metiamide or vagotomy, the latter being more effective in this respect. Thus, the chemically induced duodenal ulcer in rats resembles the human peptic ulcer disease in sensitivity to therapeutic modalities and may serve as an appropriate model to study the role of neural, hormonal, and other factors in the etiology and pathogenesis of this disorder.

The influence of vagotomy on bile kinetics in the rhesus monkey.

An increased incidence of gallstones has been reported following truncal vagotomy and gastric drainage but never conclusively proven. In the Rhesus monkey, bile composition and flow is similar to man. A model of biliary drainage was established which permits continuous monitoring of bile kinetics. Following truncal vagotomy and pyloroplasty, a significant fall in the bile acid concentration was observed, accompanied by a rise in cholesterol concentration. This resulted in an overall rise in cholesterol saturation. Similar changes in hepatic bile composition were, however, also seen following pyloroplasty alone, and suggests that the vagotomy itself may not be the important factor in producing bile changes.

The effect of truncal vagotomy on taurocholate choleresis and secretin choleresis

Mongrel dogs were prepared for cholecystectomy, chronic bile and gastric fistulas, and pyloroplasty. Taurocholate choleresis and secretin choleresis were observed before and after truncal vagotomy. Vagotomy caused minor decreases in bicarbonate output and an increase in chloride output but had no influence on bile flow, bile salt concentration, or bile salt output. Vagotomy had no influence on secretin choleresis. The findings indicate that previously observed reductions in bile salt secretion after vagotomy are due to some mechanism other than the influence of vagotomy on hepatic bile secretion.

Rat gastric mucosal oxygen tension, ulcer index, plasma gastrin and glucagon following restraint stress. Influence of vagotomy, splanchnicotomy and exogenous secretin

Restraint stress ulcers in rats were developed and procedures evaluated designed at preservation of intact gastric microcirculation (pO2). Neither prior truncal vagotomy, splanchnicotomy nor combined dissection of abdominal autonomic nerves were effective in preventing the stress mediated fall of mucosal pO2 and the rise in plasma glucagon. The ulcer index remained elevated and gastrin essentially was unchanged. Prophylactic injection of increasing doses (1, 2, 4, 8, 16 U/kg secretin maintained microcirculation at pO2-levels subnormal for unstressed animals (Vmax 15.53 mm Hg; Km. 0.99 U/kg), but simultaneously brought about a continuous rise in serum gastrin. Up to 8 U/kg plasma glucagon was higher than in saline control groups reaching a peak value with 2 U/kg when ucler index showed its nadir. Secretin therapy (4, 8 U/kg) markedly improves both mucosal pO2 and ulcer index. It is suggested that breakdown of gastric microcirculation may not be solely responsible for stress ulcer development.

The effects of vagotomy on ventilation and blood gas composition in dog, sheep and rabbit.

The influence of vagotomy on resting arterial blood gases (PaCO2 and PaO2) and on the ventilatory responses to hypercapnia and hypoxia was studied in three different species of anaesthetized animals. After bilateral cervical vagotomy resting PaCO2 generally declined. In the dog, where this was studied more fully, resting PaCO2 declined significantly (8-13 +/- 0-67 mm Hg) over several hours, but PaO2 changes were not significant. After vagotomy tidal volume (VT), but not frequency (f), increased with increasing chemical drive. It is concluded that the increase in frequency in response to increased CO2 or decreased O2 is dependent on the vagal mechanisms. Minute volume, fractional inspiratory CO2 (VE, FICO2) and minute volume, fractional inspiratory O2 (VE, FIO2) relationships have been determined. Although vagotomy may not decrease the response of minute volume of ventilation in the lower part of VE, FICO2 curves (mild hypercapnia), it flattened the upper parts of the curves in sheep and rabbits, and to a lesser extent in dogs; it seemed that there was little species difference in this respect. Ventilatory responses to graded hypoxia were close to or slightly higher than pre-vagotomy values throughout the VE, FIO2 curves in all animals.