Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging

BackgroundVagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized.MethodsIn anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium- labeled meal and scanned the rat stomach with oral contrast- enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS.Key ResultsMonophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = - .93, P < .05 for 5 Hz, R = - .85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity.Conclusions and InferencesMonophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.We investigated a possible differential effect of primarily afferent versus efferent cervical VNS on gastric motility under a range of VNS parameters. Gastric MRI data revealed that primarily afferent VNS induced stronger antral contractions relative to primarily efferent VNS. These results could serve as an index for optimizing VNS parameters for promoting gastric motility. Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155957/1/nmo13853_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155957/2/nmo13853.pd

Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years

Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS meeting

Despite the relatively high prevelance of gastroparesis and functional dyspepsia, the aetiology and pathophysiology of these disorders remain incompletely understood. Similarly, the diagnostic and treatment options for these two disorders are relatively limited despite recent advances in our understanding of both disorders.This manuscript reviews the advances in the understanding of the epidemiology, pathophysiology, diagnosis, and treatment of gastroparesis and functional dyspepsia as discussed at a recent conference sponsored by the American Gastroenterological Association (AGA) and the American Neurogastroenterology and Motility Society (ANMS). Particular focus is placed on discussing unmet needs and areas for future research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78690/1/j.1365-2982.2009.01434.x.pd

Fluorescence imaging in vivo visualizes delayed gastric emptying of liquid enteral nutrition containing pectin

BACKGROUND: Semi-solidification by gelation or increased viscosity could slow the influx of liquid enteral nutrition (EN) into the small intestine. A liquid EN formula containing pectin that gels under acidic conditions such as those found in the stomach has been developed. A new near-infrared fluorescent imaging reagent was used to non-invasively acquire real time images of gastric emptying in a murine model in vivo. We postulated that the EN formula delays gastric emptying and tested this hypothesis using imaging in vivo. METHODS: Male BALB/c mice were given an oral bolus injection of a liquid EN containing the fluorescence reagent GastroSense750 with or without pectin. The EN in the stomach was visualized in vivo at various intervals using a non-invasive live imaging system and fluorescent signals were monitored from the stomach, which was removed at 60 min after EN ingestion. RESULTS: The fluorescence intensity of signals in stomachs in vivo and in resected stomachs was lower and attenuated over time in mice given EN without, than with pectin. CONCLUSIONS: Adding a gelling agent such as pectin delayed the transit of liquid EN from the stomach. Fluorescence imaging can visualize the delayed gastric emptying of EN containing pectin

Regulation of intestinal metabolism in obesity and diabetes : studies using positron emission tomography

The global epidemic of obesity is a challenge to healthcare systems due to the increase in the incidence of type 2 diabetes (T2D) and its associated morbidities. Although the small intestine is the first absorptive organ to encounter the ingested and digesting nutrients, it has gained little attention in the research of T2D and obesity. In the present study, multimodality imaging by Positron emission tomography (PET) combined with magnetic resonance imaging (MRI) or computed tomography (CT) modalities were utilized to study intestinal blood flow and metabolic substrate uptake in healthy normal-weight controls and obese patients with T2D before and after surgical or medical treatments. In the PET imaging, we focused on intestinal blood flow and volume, fatty acid, glucose uptake using 15O-water, 15O-labeled carbon monoxide, palmitate analogue 14(RS)-[18F]fluoro-6-thia-heptadecanoic acid, ([18F]FTHA) and 2-[18F]fluoro- 2-deoxy-D-glucose ([18F]FDG), respectively. Morbidly obese subjects (mean BMI 41±4.5kg/m2) with T2D had similar blood flow in the intestine even after bariatric surgery when compared to healthy controls. The bariatric surgery was either Roux-en Y gastric bypass (n=13) or Sleeve gastrectomy (n=20). Postprandially, nutrient contact with the small intestine and infusion of glucose dependent insulinotrophic polypeptide (GIP) stimulated blood flow in the small intestine of all groups. These findings suggest that despite the adaptation changes after bariatric surgery of the intestine, postprandial blood flow regulation in the small intestine remains intact in T2D and obese individuals. Intestinal fatty acid (FA) uptake was higher in obese subjects compared to healthy counterparts and unexpectedly this increased after bariatric surgery. The FA extraction rate in the small intestine also increased after bariatric surgery and this phenomenon suggests that intestinal energy expenditure relies on high FFA-to-glucose ratio in obese patients, which persists even after weight loss. Glucose uptake in the small intestines of metformin treated study subjects with T2D was increased compared to baseline and reached the level observed in healthy study subjects in previous studies. Taken together, the data of the present study provide novel insight on the role of the small intestine in the multiorgan metabolic derangements associated with T2D. It is not known whether these changes are part of the adaptation mechanism, due to improved glycaemic control and insulin resistance breakdown or due to the fundamental pathophysiology behind T2D. The actual mechanism behind these changes should be addressed in future research.Suoliston aineenvaihdunnan säätely lihavuudessa ja diabeteksessa : positroniemissiotomografiaa käyttäen tehtyjä tutkimuksia Lihavuus on huomattavasti yleistynyt viime vuosikymmeninä ja kuormittaa terveydenhuoltoamme lisäten tyypin 2 diabeteksen ilmaantuvuutta ja yleistä sairastavuutta.Lihavuuden ja tyypin 2 diabeteksen tutkimuksessa on aiemmin keskitytty suoliston aineenvaihduntaan varsin vähän, vaikka suolisto ensimmäisenä elimenä käsittelee elimistöön tulevan ravinnon ja ruoansulatuskanavasta erittyvillä hormoneilla säätelee sokeriaineenvaihduntaa. Tutkimuksessa verrattiin suoliston verenvirtauksen ja ravintoaineiden soluunottokyvyn muutoksia ylipainoisilla tyypin 2 diabeetikoilla ja terveillä normaalipainoisilla verrokeilla käyttäen positroniemissiotomografiaa (PET) yhdistettynä rakenteelliseen magneetti- ja tietokonetomografia kuvantamiseen. Tutkittavat osallistuivat kliinisen hoitokäytännön mukaan lihavuusleikkaukseen tai käyttivät tutkimuslääkettä protokollan mukaan. PET-kuvantamisella tutkittiin suoliston verenvirtauksen ja verimäärän muutoksia sekä rasvahappojen ja sokerin soluunottokykyä käyttäen 15O-vettä, 15Oleimattua hiilimonoksidia, palmitaattianalogi 14(RS)-[18F]fluoro-6-thia-heptadekanoidi happoa ([18F]FTHA) ja 2-[18F]fluoro-2-deoxy-D-glukoosia ([18F]FDG). Sairaalloisen ylipainoisilla diabeetikoilla suoliston verenvirtaus ei poikennut terveistä kontrolleista edes lihavuusleikkauksen jälkeen. Ryhmien välisiä eroja veren virtauksessa ei todettu syömisen ja glukoosista riippuvaisen insuliinin eritystä lisäävän hormonin (GIP) annostelun jälkeen. Havainnot viittaavat siihen, että aterian jälkeinen verenvirtauksen säätely ei ole muuttunut lihavilla diabeetikoilla edes lihavuuskirurgian jälkeen, vaikka suolisto muuten sopeutuu kirurgian aiheuttamiin anatomisiin muutoksiin. Ylipainoisilla tyypin 2 diabetesta sairastavilla tutkittavilla suoliston rasvahappojen soluunottokyky todettiin lisääntyneeksi verrattuna terveisiin kontrollihenkilöihin ja odottamatta lihavuuskirurgia lisäsi kyseistä muutosta. Rasvahappojen soluunottokyvyn lisääntyminen verenkierrosta vielä lihavuuskirurgian jälkeen, osoittaa suoliston energiankäytön riippuvan korkeasta rasvahappo-sokerin käyttösuhteesta vielä laihtumisen jälkeenkin. Metformiini-lääkitys lisäsi suoliston sokerin käyttöä ja vähensi suoliston insuliiniresistenssiä, jopa normaalistaen sen terveiden tasolle. Tämä väitöskirjatutkimus osoittaa, että suolistossa tapahtuu merkittäviä aineenvaihdunnallisia muutoksia tyypin 2 diabeteksessa, ylipainossa ja lihavuusleikkauksen jälkeen. Avoimeksi jää säätelevätkö lihavuuskirurgian ja lääkehoitojen myötä lisääntyneet suoliston rasvahappojen ja sokerin käyttö koko elimistö aineenvaihduntaa vai ovatko ne seurausta suoliston sopeutumisesta muuttuneeseen energia-aineenvaihduntaan. Koska lihavuuskirurgia johtaa usein merkittävään painonlaskuun ja tyypin 2 diabeteksen paranemiseen tulisi suoliston energia-aineenvaihdunnan tutkimusta jatkaa kyseisten tautien syntymekanismin ymmärtämiseksi

A Rat Model of Human Lipid Emulsion Digestion

A better understanding of how dietary lipids are processed by the human body is necessary to allow for the control of satiation and energy intake by tailored lipid systems. To examine whether rats are a valid model of human dietary lipid processing and therefore useful for further mechanistic studies in this context, we tested in rats three lipid emulsions of different stability, which alter satiety responses in humans. Different sets of 15 adult male Sprague Dawley rats, equipped with gastric catheters alone or combined with hepatic portal vein (HPV) and vena cava (VC) catheters were maintained on a medium-fat diet and adapted to an 8 h deprivation/16 h feeding schedule. Experiments were performed in a randomized cross-over study design. After gastric infusion of the lipid emulsions, we assessed gastric emptying by the paracetamol absorption test and recorded in separate experiments food intake and plasma levels of gastrointestinal hormones and metabolites in the HPV. For an acid stable emulsion, slower gastric emptying and an enhanced release of satiating gastrointestinal (GI) hormones were observed and were associated with lower short-term energy intake in rats and less hunger in humans, respectively. The magnitude of hormonal responses was related to the acid stability and redispersibility of the emulsions and thus seems to depend on the availability of lipids for digestion. Plasma metabolite levels were unaffected by the emulsion induced changes in lipolysis. The results support that structured lipid systems are digested similarly in rats and humans. Thus unstable emulsions undergo the same intragastric destabilization in both species, i.e., increased droplet size and creaming. This work establishes the rat as a viable animal model for in vivo studies on the control of satiation and energy intake by tailored lipid systems

Feeling full and being full : how gastric content relates to appetite, food properties and neural activation

Aim: This thesis aimed to further determine how gastric content relates to subjective experiences regarding appetite, how this relation is affected by food properties and whether this is visible in neural activation changes. Method: This was studied using questionnaires, MRI of the stomach and fMRI of the brain. Randomized, controlled crossover experiments with healthy men and for one experiment women were performed. Results: MRI measurements of the stomach as opposed to an indirect measurement by proxy, such as 13C breath testing are to be preferred. We show that gastric emptying is affected by energy load, and to a much smaller extent by viscosity. Additionally we show that a thick shake containing 100 kcal will yield higher fullness sensations than a thin shake containing 500 kcal. In the chapter we name this phenomenon ‘phantom fullness’, i.e., a sense of fullness and satiation caused by the taste and mouthfeel of a food which is irrespective of actual stomach fullness. A liquid meal followed by a drink of water empties about twice as fast in the first 35 minutes compared to the same amount of water incorporated within the liquid meal. Using MRI we were able to show layering within the stomach and increased emptying of this watery layer. With 300mL of increased gastric content inducing distention, appetite was lowered. Ingestion led to significant changes in activation in the right insula and parts of the left and right inferior frontal cortices over time. Women retain significantly more fluid after a carbonated drink in their stomach than men. When comparing correlations between subjective ratings and intragastric liquid and gas and total gastric volume, nausea and fullness correlated strongest with the liquid fraction within the stomach, bloating strongest with total gastric volume. Conclusion: There are marked differences betweengastric content and subjective experiences regarding appetite. Viscosity is a main driver of these differences. Combined gastric MRI and brain fMRI measurements need to be performed to understand this further.</p