The effect of mirtazapine on gastric accommodation, gastric sensitivity to distention, and nutrient tolerance in healthy subjects

Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of different regions of the stomach, specifically the fundus, antrum, and pylorus. Several of the important physiological principles were based on in vivo animal studies that led to the appreciation of regional function and control mechanisms. These include the roles of the extrinsic parasympathetic vagal innervation, the gastric enteric nervous system and electrical syncytium consisting of pacemaker cells and smooth muscle cells, and duodenogastric reflexes providing feedback regulation following the arrival of food and hydrogen ions stimulating the release of hormones and vagal afferent mechanisms that inhibit gastric motility and stimulate pyloric contractility. Further insights on the role of regional motor functions in gastric emptying were obtained from observations in patients following diverse gastric surgeries or bariatric procedures, including fundoplication, Billroth I and sleeve gastrectomy, and sleeve gastroplasty. Antropyloroduodenal manometry as well as measurements of pyloric diameter and distensibility index provided important assessments of the role of antral hypomotility and pylorospasm, and these constitute specific targets for individualized treatment of patients with gastroparesis. Moreover, in patients with upper gastrointestinal symptoms suggestive of gastroparesis, the availability of measurements of gastric accommodation as well as pharmacological agents to reduced gastric sensitivity or enhance gastric accommodation provide additional specific targets for individualized treatment. It is anticipated that, in the future, such physiological measurements will be applied in patients to optimize choice of therapy, possibly including identifying the best candidate for pyloric interventions.

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Transcutaneous Electrical Acustimulation Synchronized with Inspiration Improves Gastric Accommodation Impaired by Cold Stress in Healthy Subjects

Gastroenterology ◽

10.1016/s0016-5085(17)33195-5 ◽

2017 ◽

Vol 152 (5) ◽

pp. S937

Author(s):

Gang Ma ◽

Bo Zhang ◽

Pingping Hu ◽

Feng Xu ◽

Jieyun Yin ◽

...

Keyword(s):

Cold Stress ◽

Healthy Subjects ◽

Gastric Accommodation

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Influence of sildenafil on gastric sensorimotor function in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00419.2003 ◽

2004 ◽

Vol 287 (5) ◽

pp. G988-G992 ◽

Cited By ~ 45

Author(s):

Giovanni Sarnelli ◽

Daniel Sifrim ◽

Jozef Janssens ◽

Jan Tack

Keyword(s):

Gastric Emptying ◽

Healthy Subjects ◽

Soluble Guanylate Cyclase ◽

Therapeutic Potential ◽

Muscle Relaxation ◽

Gastric Wall ◽

Gastric Volume ◽

Gastric Fundus ◽

Smooth Muscle Relaxation ◽

Gastric Accommodation

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo ( n = 13) or sildenafil, 50 mg ( n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 ± 15 vs. 163 ± 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 ± 38 vs. 253 ± 42 ml, P < 0.05) or 60 min (348 ± 49 vs. 247 ± 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 ± 4 vs. 56 ± 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.

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Influence of sumatriptan on gastric accommodation and on antral contraction in healthy subjects assessed by ultrasonography

Neurogastroenterology & Motility ◽

10.1111/j.1365-2982.2012.01984.x ◽

2012 ◽

Vol 24 (12) ◽

pp. 1083-e564 ◽

Cited By ~ 6

Author(s):

Y. Sekino ◽

E. Yamada ◽

E. Sakai ◽

H. Ohkubo ◽

T. Higurashi ◽

...

Keyword(s):

Healthy Subjects ◽

Gastric Accommodation

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Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.275.2.g314 ◽

1998 ◽

Vol 275 (2) ◽

pp. G314-G321 ◽

Cited By ~ 16

Author(s):

Miriam Thumshirn ◽

Michael Camilleri ◽

Russell B. Hanson ◽

Donald E. Williams ◽

Alfred J. Schei ◽

...

Keyword(s):

Lower Esophageal Sphincter ◽

Pain Perception ◽

Motor Dysfunction ◽

Gastric Distension ◽

Gastric Accommodation ◽

Standard Meal ◽

Sphincter Function ◽

Rumination Syndrome ◽

Gastric Sensitivity ◽

Esophageal Sphincter

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls ( P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls ( P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension ( P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.

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Gastric accommodation in non-ulcer dyspepsia and the roles ofHelicobacter pylori infection and vagal function

Gut ◽

10.1136/gut.44.1.55 ◽

1999 ◽

Vol 44 (1) ◽

pp. 55-64 ◽

Cited By ~ 108

Author(s):

M Thumshirn ◽

M Camilleri ◽

S B Saslow ◽

D E Williams ◽

D D Burton ◽

...

Keyword(s):

Gastric Emptying ◽

Minnesota Multiphasic Personality Inventory ◽

Cold Water ◽

Gastrointestinal Symptoms ◽

Therapeutic Approaches ◽

Gastric Accommodation ◽

Gastric Sensitivity ◽

Non Ulcer Dyspepsia ◽

H Pylori ◽

Vagal Function

BackgroundThe pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood.AimsTo compare gastric motor and sensory functions in Helicobacter pyloripositive or negative patients with non-ulcer dyspepsia.PatientsSeventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls.MethodsThe following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI).ResultsGastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated toH pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent amongH pylori positive patients (4/5H pylori positive versus 4/12H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI.ConclusionImpaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

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Contribution of different triggers to the gastric accommodation reflex in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00046.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. G902-G906 ◽

Cited By ~ 14

Author(s):

Pieter Vanden Berghe ◽

Pieter Janssen ◽

Sebastien Kindt ◽

Rita Vos ◽

Jan Tack

Keyword(s):

Healthy Subjects ◽

Gastric Retention ◽

Fixed Rate ◽

Proximal Stomach ◽

Gastric Accommodation ◽

Sham Feeding ◽

Early Satiety ◽

Cephalic Phase ◽

And Control ◽

Nasointestinal Tube

Accommodation of the stomach consists of a vagally mediated relaxation of the proximal stomach, providing the meal with a reservoir. Our aim was to study whether, similar to other vagally mediated processes, the accommodation reflex is also determined by cephalic, oropharyngeal, gastric, and intestinal phases. Eleven healthy subjects underwent in randomized order five gastric barostat studies and two satiety drinking tests. In all studies, isobaric tone measurements (at minimal distending pressure + 2 mmHg) were performed 20 min before and 20 min after a nutrient stimulus. The stimuli included only visual and olfactory exposure to a meal (cephalic stimulation), taking liquid nutrient in the mouth without swallowing (sham feeding), ingestion of a 200-ml 300-kcal nutrient meal with blocked outflow to the pylorus (gastric retention), and meal infusion through a nasointestinal tube (duodenal instillation), or normal ingestion (control). During satiety testing, subjects ingested liquid nutrient at a fixed rate of 15 ml/min until maximum satiety, with an inflated or deflated intrapyloric balloon assembly. Progressively bigger gastric relaxatory responses were seen with cephalic stimulation (18 ± 19 ml), sham feeding (54 ± 21 ml), gastric retention (95 ± 47), duodenal instillation (144 ± 33), and control (232 ± 33 ml). The amount of nutrient ingested at maximum satiety was significantly lower with an inflated intrapyloric balloon (1,223 ± 103 vs. 1,392 ± 124 ml, P < 0.05). The accommodation reflex in humans lacks a cephalic phase, but it can be activated from the oropharynx, the stomach, and the duodenum. Blocking passage to the duodenum significantly decreases the amplitude of the accommodation reflex and induces early satiety.

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Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects

Journal of Gastroenterology and Hepatology ◽

10.1111/jgh.13168 ◽

2016 ◽

Vol 31 (3) ◽

pp. 561-566 ◽

Cited By ~ 17

Author(s):

Zhihui Huang ◽

Nina Zhang ◽

Feng Xu ◽

Jieyun Yin ◽

Ning Dai ◽

...

Keyword(s):

Healthy Subjects ◽

Gastric Accommodation

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Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00086.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. G278-G284 ◽

Cited By ~ 87

Author(s):

Kwang-Jae Lee ◽

Rita Vos ◽

Jozef Janssens ◽

Jan Tack

Keyword(s):

Healthy Subjects ◽

Gastric Fundus ◽

Acid Exposure ◽

Gastric Distension ◽

Gastric Accommodation ◽

Double Blind ◽

Gastric Tone ◽

Acid Infusion ◽

Duodenal Acidification ◽

Double Blind Design

Decreased acid clearance and increased exposure to acid of the duodenum have been reported in a subset of functional dyspepsia patients. However, the mechanism by which increased duodenal acid exposure may affect symptoms is unclear. The aim of the present study was to investigate the effects of duodenal acidification on proximal gastric tone and mechanosensitivity in humans. An infusion tube with a pH electrode attached was positioned in the second part of the duodenum, and a barostat bag was located in the gastric fundus. In 12 healthy subjects, fundic tone and sensitivity to distensions were assessed before and during duodenal infusion of 0.1 N hydrochloric acid or saline in a randomized, double-blind design. In 10 healthy subjects, meal-induced accommodation was measured during duodenal infusion of acid or saline. Acid infusion in the duodenum significantly increased fundic compliance and decreased fasting fundic tone. This was accompanied by a significant decrease in the pressures and the corresponding wall tensions at the thresholds for discomfort. During infusion of acid, significantly higher perception and symptom scores were obtained for the same distending pressures. The meal-induced fundic relaxation was significantly smaller during acid infusion compared with saline infusion. In conclusion, duodenal acidification induces proximal gastric relaxation, increases sensitivity to gastric distension, and inhibits gastric accommodation to a meal. Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms.

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