Claudia P. Sanmiguel

Effect of electrical stimulation of the LES on LES pressure in a canine model

Gastric electrical stimulation modulates lower esophageal sphincter pressure (LESP). High-frequency neural stimulation (NES) can induce gut smooth muscle contractions. To determine whether lower esophageal sphincter (LES) electrical stimulation (ES) can affect LESP, bipolar electrodes were implanted in the LES of four dogs. Esophageal manometry during sham or ES was performed randomly on separate days. Four stimuli were used: 1) low-frequency: 350-ms pulses at 6 cycles/min; 2) high-frequency-1: 1-ms pulses at 50 Hz; 3) high-frequency-2: 1-ms pulses at 20 Hz; and 4) NES: 20-ms bipolar pulses at 50 Hz. Recordings were obtained postprandially. Tests consisted of three 20-min periods: baseline, stimulation/sham, and poststimulation. The effect of NES was tested under anesthesia and following IV administration of l-NAME and atropine. Area under the curve (AUC) and LESP were compared among the three periods, by ANOVA and t-test, P < 0.05. Data are shown as means +/- SD. We found that low-frequency stimulation caused a sustained increase in LESP: 32.1 +/- 12.9 (prestimulation) vs. 43.2 +/- 18.0 (stimulation) vs. 50.1 +/- 23.8 (poststimulation), P < 0.05. AUC significantly increased during and after stimulation. There were no significant changes with other types of ES. With NES, LESP initially rose and then decreased below baseline (LES relaxation). During NES, N(G)-nitro-l-arginine methyl ester increased both resting LESP and the initial rise in LESP and markedly diminished the relaxation. Atropine lowered resting LESP and abolished the initial rise in LESP. In conclusion, low frequency ES of the LES increases LESP in conscious dogs. NES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.

Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control

Background: The TANTALUS® System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption. Method: Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 ± 1 kg/m2, hemoglobin A1c [HbA1c] 8.5 ± 0.2%). Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period. Results: Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 ± 0.7% to 7.6 ± 1%, p < .01. Weight was also significantly reduced from 107.7 ± 21.1 to 102.4 ± 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss (R 2 = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only). Conclusions: Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network. Conclusions 1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity.

Neural gastrointestinal electrical stimulation enhances colonic motility in a chronic canine model of delayed colonic transit

Abstract  Neural gastrointestinal electrical stimulation (NGES) induces sequential contractions and enhances emptying in acute canine gastric and colonic models. This study was set to determine (i) the effect of NGES in a chronic canine model of delayed colonic transit and (ii) possible mechanism of action. Four pairs of electrodes were implanted in the distal colon of nine mongrel dogs. Delayed colonic transit was induced by diphenoxylate/atropine and alosetron. Transit was fluoroscopically determined by the rate of evacuation of radiopaque markers, and was tested twice in each dog, in random order, on and off stimulation. Two stimulation sequences, separated by 1 min, were delivered twice a day via exteriorized electrodes. Colonic manometry during stimulation was performed before and after intravenous (i.v.) injection of 1 mg of atropine. Complete evacuation of all markers was significantly shortened by NGES, from 4 days to 2 days, interquartile range 3–4 days vs 2–3 days, respectively, P = 0.016. NGES induced strong sequential contractions that were significantly diminished by atropine: 190.0 ± 14.0 mmHg vs 48.7 ± 19.4 mmHg, respectively (P < 0.001). NGES induces strong sequential colonic contractions and significantly accelerates movement of content in a canine model of delayed colonic transit. The effect is atropine sensitive.

Gut Microbiome and Obesity: A Plausible Explanation for Obesity

Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest–host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review, we summarize the current evidence for possible mechanisms underlying gut-microbiota-induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions, and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.

Irritable pouch syndrome is characterized by visceral hypersensitivity

Background: Irritable pouch syndrome (IPS) is a functional disorder in patients with ileal pouch–anal anastomosis (IPAA), which presents with symptoms in the absence of structural abnormalities of the pouch. Thus, it resembles other functional disorders, such as irritable bowel syndrome characterized by visceral hypersensitivity in the presence of normal rectal biomechanics. The aim was to assess pouch biomechanics and perception of balloon distension in different groups of subjects with IPAA and to correlate the findings with clinical features. Methods: Pouch tone, compliance, and sensation to balloon distension were measured in 18 patients with IPS, 11 patients with active pouch inflammation (pouchitis or Crohns disease of the pouch), and 12 asymptomatic subjects with normal pouches. All patients were recruited from a subspecialty Pouchitis Clinic. Results: Scores of sensation of gas, urge to defecate, and pain measured by visual analog scales at various distension pressures were significantly higher in IPS than pouchitis and normal pouch patients. Pouch tone was comparable among the groups and compliance was reduced in the pouchitis group. The visual analog scale showed a trend of correlation with the Pouchitis Disease Activity Index symptom scores in IPS. Conclusions: IPS, like other gut functional disorders, is characterized by visceral hypersensitivity, with normal pouch biomechanics. (Inflamm Bowel Dis 2011)

Association between Gastric Electromechanical Activity and Satiation in Dogs

Objective: The objective of this study was to validate the use of impedance for measurement of antral contractions and to determine the relationship between food‐induced changes in gastric motility and satiation.

Circadian patterns of gastric electrical and mechanical activity in dogs.

Abstract  Gastric motor function assessment, in humans and animals, is typically performed for short recording periods. The aim of this article was to monitor gastric electrical and motor activity in the antrum and fundus simultaneously, for long periods, using a new implantable system. Ten dogs were implanted with fundic and antral electrodes for assessment of impedance and electrical activity. Dogs were studied while in cages, for periods of 22–26 h. From late evening and until feeding on the next day, slow wave (SW) rhythm demonstrated a distinct pattern of intermittent pauses (mean duration = 22.8 ±4.1 s) that delineated groups of SW’s. Phasic increases in fundic tone were seen mostly in association with SW pauses, and were highly correlated with antral contractions, R2 = 0.652, P < 0.05. The SW rate (events per minute) in the postprandial period, fasting and night time was 4.2 ± 0.2, 5 ± 0.2 and 4.7 ± 0.3, respectively, P < 0.05 postprandial vs other periods. Antral and fundic mechanical activities were highly correlated during fasting, particularly at night. This novel method of prolonged gastric recording provides valuable data on the mechanical and electrical activity of the stomach, not feasible by current methods of recording. During fasting, fundic and antral motor activities are highly correlated and are associated with periodic pauses in electrical activity.

The use of gastric electrical signals for algorithm for automatic eating detection in dogs

Abstract  Food ingestion increases fundic impedance (FI) and reduces antral slow wave rate (SWR).

Dynamics of Level of Randomness of Electrogastrograms Can Be Indicative of Gastric Electrical Uncoupling in Dogs

Gastric electrical uncoupling is the lack ofelectrical synchronization in different parts of thestomach. The aim of this study was to investigate theimpact of gastric electrical uncoupling on the level of randomness of canine electrogastrograms(EGG). Electrogastrograms were obtained from 11unconscious acute dogs. Gastric electrical uncouplingwas produced surgically by performing two consecutivecircumferential cuts through the entire thickness of thegastric muscle layer. Three separate 1/2-hreight-channel bipolar EGGs were obtained from each dogin the basal state and after each cut. The signals wereamplified using amplifiers with a flexible frequencyrange, digitized with 10-Hz sampling frequency, and4.27-min portions of the digital EGGs weResubjected toa turning point test for randomness. The number of turning points (NTPs) was determined fromsuccessive time intervals calculated from all EGGchannels. Distributions of NTPs were calculated for eachdog. An average NTPs (ANTP) for each dog in a givenstate (basal, after the first cut, and after thesecond cut) was calculated from the ANTPs of allchannels. In six of 11 dogs the ANTP were greater afterthe first cut. The number rose to nine of 11 dogs after the second cut. In only 45% of the dogs werethe ANTP distributions significantly different (P <0.01) after the first cut (sensitivity 45%). After thesecond cut the sensitivity rose to 64%. In two specific EGG channels NTP distribution wassignificantly different (P < 0.01) in nine of 11 dogs(sensitivity: 82% ) after the second cut. The dynamicsof the level of randomness in EGG can be indicative of severe gastric electrical uncoupling. SomeEGG channel configurations are moResensitive thanoThers in recognizing gastric electricaluncoupling.