Influence of vagal nerve stimulation on food intake and body weight--results of experimental studies.

The paper reviews recent advances in vagal nerve stimulation for the control of food intake and body weight. The vagal nerves are the predominant pathway in the "brain-gut axis" responsible for short term regulation of food intake. Stimulation of afferent vagal traffic attenuates food intake by vagal projections to nucleus tractus solitarius, arcuate nucleus and its convergence's to thalamic center of satiety. A few studies have been published in this field so far. All of them are consistent and show significant decrease in body mass during vagal stimulation. Due to promising results of experimental studies, clinical trials are expected in the near future.

The effects of baclofen on the feeding behaviour and body weight of vagally stimulated rats.

UNLABELLED: It is hypothesised that the GABA(B) receptor agonist baclofen increases or has no effect on food intake, and electrical stimulation of vagal nerves decreases food intake. The aim of this study was to evaluate the effects of baclofen in vagally stimulated rats. MATERIAL AND METHODS: Thirty two Wistar rats were divided into five groups: group A scheduled for microchip implantation for vagal stimulation, group B for sham operation, group C for microchip implantation and baclofen medication, group D for baclofen medication only and group E for gastric motility evaluation under influence of baclofen. The following parameters were then evaluated: food intake and body mass, gastric motility, leptin, insulin, and glucose serum levels. RESULTS: In the comparison of groups B and A, daily food intake and body weight gain decreased by 17% (p<0.05) and by 22% (p<0.05), respectively. Baclofen alone (group D) did not significantly change either food intake nor diurnal body weight compared to the controls, but when used in conjunction with the microchip (group C) it did significantly reduce effect of vagal neuromodulation (p<0.05). Furthermore, a significant decrease in leptin and glucose levels was detected in group C: 677 to 165 pg/ml (p<0.05) and 5,93 to 4,88 mmol/l (p<0.05), respectively. The administration of baclofen stimulated significantly gastric motility and elicited irregular motor migrating complex (327+/-200 against control 255+/-52 cmH2O/s). CONCLUSIONS: These results suggest that microchip vagal neuromodulation through increased vagal afferent activity induces an alteration in the feeding behaviour and decreases nocturnal food intake and body weight. These effects were partially attenuated by baclofen. The data suggests that GABA(B) receptors play an important role in the pathomechanism of attenuation of food intake induced by vagal nerve stimulation.

Encoding meal in integrated vagal afferent discharge.

Vagal afferents are integral part of the negative feedback loop induced by constitution and size of food stomach and jejunum. Aim of this study was to assess vagal discharge in response to food and gastric distension in rats. Electrophysiological recordings of vagal afferents in fasted (n=32), fed rats (n=20) and during gastric balloon distension (n=12) were performed. After 60 minutes of fasted nerve recording tube feeding was done. Fasted rats also underwent gastric distension via oesophagus. Vagal afferents discharges were analysed with dual time-amplitude window discriminator. Total vagal afferent discharge in fasted and fed rats revealed 0.3 +/- 0.12 vs 0.56 +/- 0.22 Hz (p<0.05). We observed two distinct discharge patterns: high amplitude low frequency (HALF) and low amplitude high frequency (LAHF). HALF spikes were observed more frequent in fasted than in fed rats (0.05 +/- 0.02 vs. 0.03 +/- 0.016 Hz (p<0.05). Conversely LAHF spikes in fed rats predominated over their occurrence in fasted rats: 0.52 +/- 0.2 vs. 0.25 +/- 0.12 Hz (p<0.05). Left vagal afferents discharge rises with gastric distension of 6, 8 and 10 ml and were: 0.46 +/- 0.22 Hz, 0.65 +/- 0.31 Hz, 0.86 +/- 0.33 Hz (p<0.05) respectively. Similar discharge showed right vagal afferents: 0.41 +/- 0.08 Hz, 0.51 +/- 0.13 Hz and 0.77 +/- 0.27 Hz (p<0.05) for 6, 8 and 10 ml of distension, respectively. We conclude that interdigestive information from gastrointestinal tract is encoded in high amplitude low frequency of spikes pattern in the vagus nerves.

Effects of vagal neuromodulation and vagotomy on control of food intake and body weight in rats.

Food induced neurohumoral signals are conduced to data processing brain centers mainly as vagal afferent discharge resulting in food intake regulation. The aim of this study was to evaluate effects of vagal nerve neuromodulation in control of food intake with fed-pattern microchip (MC) pacing. Experiments were performed on 60 rats divided on 5 groups: I group 0,05Hz left vagal pacing, II - pacing of both vagal nerves with MC 0,05Hz, III- left vagal MC 0,1Hz pacing, IV - pacing of both vagal nerves with MC 0,1 Hz was performed. In group V left vagal pacing was combined with right side abdominal vagotomy. Body weight and total food intake decreased by 12% and 14% (I), 26% and 30%(II), 8% and 21%(III), 14% and 30%(IV), 38% and 41%(IV), respectively (p<0.05). Effects of both vagal nerves stimulation on final body weight and food intake was significantly more effective than only single nerve MC pacing however most effective was stimulation with 0,1Hz combined with right vagotomy. We conclude that vagal stimulation reduce food intake and body weight by increasing vagal afferent signals. Our results suggest that information in vagal afferents can be modulated resulting in changes of feeding behaviour and body weight.

The cybergut. An experimental study on permanent microchip neuromodulation for control of gut function.

UNLABELLED: Acute electrical stimulation of vagal nerve changes gut motility, secretion as well as absorption, and it may have effect on food intake and satiety regulation. The aim of the study was to evaluate the effect of permanent microchip mediated neuromodulation (McNm) of vagal afferent activity on GI function and body mass in the experimental model. MATERIAL AND METHODS: Two-steps study was performed. In the first step (evaluation of food intake) 16 rabbits were divided in two groups, 8 animals each. Group A was subjected to microchip mediated neuromodulation (McNm), and control group B was sham operated. In both groups laparotomy and vagal exploration were performed. In the second step pathomechanism of Mc action was analysed in fourteen Wistar rats divided in two groups (C and D), 7 animals each. Group C was subjected to Mc implantation and gastrostomy placement and group D (controls) to gastrostomy placement alone. RESULTS: Food intake and body mass significantly decreased in group A after Mc implantation compared with the preoperative period and control group B. No differences were found in the frequency of gastric contractions between groups C and D, however, their amplitude was significantly stronger in group C. Neuromodulation had significant effect on BAO without changes in MAO levels. CONCLUSIONS: Low frequency permanent vagal neuromodulation affects gastric function and influences food intake in the experimental model.

Pancreatic carcinoma-induced changes in gastric myoelectric activity and emptying.

BACKGROUND/AIMS: Twenty patients with histologically confirmed pancreatic carcinoma without any endoscopic evidence of gastroduodenal obstruction were included in the study. The aim was to determine changes in gastric myoelectric activity and liquid/solid gastric emptying induced by pancreatic tumor. METHODOLOGY: According to TNM/UICC classification patients were divided into two groups A (T2) and B (T3) due to extent of tumor invasion (mainly to retroperitoneum space). In all patients electrogastrography, solid and liquid gastric emptying tests were performed. RESULTS: In the majority of patients of groups A and B the most commonly reported complaints included upper abdominal pain (60% vs. 80%) and icterus (80% vs. 60%). Dyspeptic symptoms were observed in 40% patients of group A and 90% in group B. In group electrogastrography recordings showed dysrhythmia patterns, mostly bradygastria, in 50% of group A patients and in 80% of group B. Liquid/solid gastric emptying were delayed in 20/40% of group A patients and 50/80% of group B. Disorders of gastric myoelectric activity and emptying correlated with tumor stage and location across analyzed groups but not with histology and hyperbilirubinemia levels. CONCLUSIONS: It was observed that solid gastric emptying is affected earlier compared to liquid gastric emptying. Delayed gastric emptying may be attributed to gastric dysrhythmia and/or abdominal pain but not mechanical effects of tumor growth that occur during the course of disease.

Microchip vagal pacing reduces food intake and body mass.

BACKGROUND/AIMS: Morbid obesity is an increasing problem worldwide. In many patients pharmacotherapy is ineffective and these cases are treated by surgery. Different types of gastroplasty and gastric bypasses have been described. However, all of these ablative surgical methods are irreversible and often replace obesity by other disorders. Neuromodulation of vagal activity is a method of inducing significant changes in stomach motility. We developed a pre-programmed microchip able to pace vagal afferent activity by changing current parameters. The aim of our study was to evaluate long-term effects of vagal neuromodulation on food intake and body mass in rabbits. METHODOLOGY: Twenty-seven healthy male adult New Zealand white rabbits were included into the study and divided into three groups: A, B and C, 9 animals each. Microchips were implanted by laparotomy access. Anesthesia was obtained by continuous intravenous infusion of propofol. Microchips were fixed in the preperitoneal pocket and two electrodes were positioned on the posterior vagus in group A by forward, and in group B by backward pacing. Control group C was sham operated by laparotomy and only vagal nerves preparation was performed. The following parameters were estimated: daily solid food and liquids intake, amount of feces, body mass and heart rate. RESULTS: Within four weeks after operation body mass in group B had decreased up to 12% (P = 0.029), whereas in group A and C changed to -3% and +2%, respectively. An 87% solid food intake was observed in group A, 60% in group B (P < 0.01), and 143% in group C, compared to preoperative period. No significant differences were observed between groups A, B and C for liquids intake. Total feces weight changes corresponded to solid food intake. Heart rate decreased intraoperatively to 78% and 74% in groups A and B, respectively. CONCLUSIONS: Microchip mediated functional gastroplasty significantly reduces food intake and body mass. Obtained results encourage using similar treatment in morbid obesity human patients. However, further studies are required.

Effects of continuous microchip (MC) vagal neuromodulation on gastrointestinal function in rats.

Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250-350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5-30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 +/- 2.5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid--intragastrically) almost doubled amount of bursts to 12 +/- 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 +/- 4.8 vs control 35.5 +/- 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 +/- 9.08 vs control 23.56 +/- 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 +/- 9.3 vs control 98.5 +/- 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 +/- 0.8 vs 1.17 +/- 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 +/- 0.35 vs 0.68 +/- 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 +/- 0.14 vs 0.14 +/- 0.12 mmol/30 min, p < 0.05) but MAO did not change in MC rats (0.37 +/- 0.25 vs 0.42 +/- 0.28 mmol/30 min, p 0.05). Gastric emptying of isotonic solution increased by 10% (90.46 +/- 5.34 vs 80.39 +/- 9.95) percent of marker passing to duodenum/5 min, p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight.

Neuromodulation of vago-vagal reflex.

Functional gastrointestinal disorders are poorly understood. The lack of clear classification and definition of these disturbances interferes with unsatisfying treatment. The possible explanation has been recently looked up in the changes of brain-gut axis interactions. Simultaneously microelectronics has been made tremendous progress in the cooperation with medical sciences lately. Electronic microcircuits have become widely used in neurosciences because of their many advantages compared to standard investigational devices. Implantable microchips facilitate studies of nervous system allowing carrying on chronic experiments with minimal damage to surrounding organs. Neuromodulation of autonomic nerves gives promise for treatment refractory disturbances of gut motility.

[A case of isolated gallbladder rupture after blunt abdominal trauma]. / Przypadek izolowanego pekniecia pecherzyka zólciowego w nastepstwie tepego urazu jamy brzusznej.

Isolated injury of gall bladder as a result of blunt abdominal trauma is very rare. We report a case of 39 year old man, who was admitted to our Clinic during emergency. He presented upper right quadrant abdominal pain, increasing on palpation and guarding. Ultrasound examination showed fluid under liver. Disruption of the neck of the gall bladder was found during laparotomy. Cholecystectomy was performed. Patient was discharged from hospital five days after the operation.

Early effects of standard and pylorus-preserving pancreatectomy on myoelectric activity and gastric emptying.

BACKGROUND/AIMS: The main concern about pylorus preserving pancreatectomy (PPP) is delayed gastric emptying (GE). Both cancer and surgical procedures cause damage to the enteric nervous system and induce profound changes in gastric motility and emptying. The aim was to evaluate the effects of primary disease and type of surgical procedure used (standard pancreatoduodenectomy, SP vs. PPP) on myoelectric activity (MA), and solid and liquid GE in pancreatectomy patients. METHODOLOGY: Twenty-eight subjects were included, 18 after Whipple (group A) and 10 after a Traverso (group B) procedure. MA was captured by cutaneous electrodes (Synectics) and simultaneously LGE tested with ultrasonography. On separate days, the SGE of a radiolabelled meal was measured. MA and GE studies were done before and within three months after surgery. RESULTS: Before surgery LGE/SGE were delayed in 5/8 patients in group A and 2/2 in group B. Gastric dysrhythmia was observed in 6 patients in group A and 1 in group B. After PPP, the nasogastric tube was removed within 8.4+/-4.9 days and after SP within 4.6+/-4.1 days. GE studies showed accelerated LGE/SLG in 16/12 and delayed in 6/5 patients, respectively, in group A and B. Dysrhythmia was observed in 16 patients in group A and in 4 in group B. There was a strong relationship between SGE delay and dysrhythmia in patients after PPP. CONCLUSIONS: We conclude that papilla of Vater neoplasia damages mechanisms responsible for gastric emptying to a lesser extent than pancreatic cancer. In patients after PPP, post-operative MA disturbances are partially responsible for delayed GE.

[Gastric motility disturbances in pancreatic cancer patients]. / Zaburzenia czynnosci motorycznej zoladka u pacjentów z rakiem trzustki.

Eighteen patients with confirmed pancreatic carcinoma without endoscopic evidence of mechanical gastroduodenal obstruction were included in the study. Aim was to determine changes in gastric myoelectric activity and liquid emptying (LGE) induced by pancreatic tumor growth. According TNM/UICC classification patients were divided in two groups A (T2) and B (T3) due to extend of expansion. Dyspeptic symptoms were observed in 4 patients of group A and 8 in group B. In group A dysrhythmic patterns of gastric myoelectric activity mostly bradygastria type were observed in 5 of patients and 8 in group B. LGE were delayed in 2 in group A and 5 in group B respectively. Disordered gastric myoelectric activity and emptying correlated with tumor stage and location. Delayed gastric emptying may be attributed to gastric dysrhythmia and abdominal pain that occur during the course of disease due to splamchnic plex infiltration.

[Stomach electrostimulation--new possibility for treating gastroparesis]. / Elektrostymulacja zoladka--nowa mozliwosc leczenia gastroparezy.

This paper presents a large range of methods of human gastric pacing. Based on our own experience and literature authors discuss a variety of pacing models, current parameters and place of stimulation. We described a new method of intragastric stimulation as a method of treatment of postoperative, pharmacotherapy resistant gastroparesis. Five patients were included in to the study (3 male and 2 female). The current parameters were as follow: square profile, amplitude 2V (2mA), frequency 6 ips.p.m., duration 3 hours. Two electrodes located on nasogastric catheter (external diameter 1.5 mm) were placed in antral region of the stomach and connected to the computer preprogrammed stimulator. Electrostimulation was accompanied by the continuous cutaneous EGG monitoring (Synectics Sweden). Excellent results were obtained in 3 patients (60%) with disappearance of symptoms, rumbling, normalization in gastric myoelectric rhythm (2-4 cpm > 85%) and with increase in amplitude (average 250%). In one patient with the gastrectasia, symptoms returned next day and stimulation had to be repeated for several days. In another one results were not satisfying. Authors conclude that gastric pacing has made tremendous progress fast developing method in last decade and in most patient is efficient for treatment postoperative gastroparesis.

[The effect of pentagastrin on calcium ion concentration in gastric juice]. / Wplyw pentagastryny na stezenie wapnia w soku zoladkowym.

Calcium concentration in gastric juice is lower then other electrolytes. The mechanism of its transport remained unknown. The aim of the study was to evaluate influence of pentagastrin on calcium concentration in gastric juice in humans. Ten patients were examined (4 females and 6 males, mean age 46.8 range 33-67), four with duodenal ulcer, three with achalasia cardiae and three with Addison-Biermer anemia. Pentagastrin--PG (Cambridge Laboratories, Newcastle, United Kingdom) was injected subcutaneously after overnight fast in dose of 6 micrograms/kg of body weight. Nosogastric tube was located in body of the stomach near large curvature and connected to suction of--40 mmHg pressure. Gastric juice was collected during subsequent five 15 minutes periods (first fasted and four periods after stimulation with PG). Calcium concentration was measured in each sample by fluorescentic titration method with EGTA. Statistic analysis was performed with student "t" test. Mean fasted and stimulated calcium concentrations were 0.83; 0.44; 0.54; 0.37 and 0.95 mmol/l respectively. Ca2+ concentration range in fasted state from 0.21 to 1.75 mmol/l and from 0.07 to 0.27 mmol/l by maximal stimulation. Calcium concentration decreased immediately after stimulation (significance p = 0.0025). This strong effect persisted throughout the period of stimulation. Calcium output was 0.064; 0.029; 0.032; 0.018 and 0.17 mmol/15 min respectively. Two phases of decrease of the calcium output were observed: first, fast decrease immediately after pentagastrin injection and second, slower, between 30 and 45 minute after stimulation (p < 0.01 and 0.02 respectively). Calcium concentration in gastric juice decreases after stimulation with pentagastin (p = 0.0025). Calcium concentration was lower in Addison-Biermer anemia and higher in duodenal ulcer patients then in healthy control. We conclude that calcium ions are not actively secreted by gastric mucosa. Their presence in gastric juice is a result of leak from mucosal cells and remains opposite to their metabolic activity.

[Autonomic nervous system dysfunction in Parkinson's disease evaluated by the heart rhythm variability test]. / Zaburzenia ukladu autonomicznego w chorobie Parkinsona oceniane testem zmiennosci rytmu serca.

It is well recognized that autonomic dysfunction are common in Parkinson's disease (PD). Fourteen patients with early PD and 8 patients with advanced PD aged from 38-71 were investigated. Heart rate variability at rest differ significantly between patients with advanced PD and age-matched controls. Cardiovascular autonomic dysfunction in PD mainly affects parasympathetic but also sympathetic system, and occurs only in advanced cases. Heart rate variability is a useful non-invasive test to assess autonomic dysfunction in PD.