Gastric supply manipulation to modulate ghrelin production and enhance vascularization to the cardia: proof of the concept in a porcine model.

INTRODUCTION: Selective embolization of the left-gastric artery (LGA) reduces levels of ghrelin and achieves significant short-term weight loss. However, embolization of the LGA would prevent the performance of bariatric procedures because the high-risk leakage area (gastroesophageal junction [GEJ]) would be devascularized. AIM: To assess an alternative vascular approach to the modulation of ghrelin levels and generate a blood flow manipulation, consequently increasing the vascular supply to the GEJ. MATERIALS AND METHODS: A total of 6 pigs underwent a laparoscopic clipping of the left gastroepiploic artery. Preoperative and postoperative CT angiographies were performed. Ghrelin levels were assessed perioperatively and then once per week for 3 weeks. Reactive oxygen species (ROS; expressed as ROS/mg of dry weight [DW]), mitochondria respiratory rate, and capillary lactates were assessed before and 1 hour after clipping (T0 and T1) and after 3 weeks of survival (T2), on seromuscular biopsies. A celiac trunk angiography was performed at 3 weeks. RESULTS: Mean (±standard deviation) ghrelin levels were significantly reduced 1 hour after clipping (1902 ± 307.8 pg/mL vs. 1084 ± 680.0; P = .04) and at 3 weeks (954.5 ± 473.2 pg/mL; P = .01). Mean ROS levels were statistically significantly decreased at the cardia at T2 when compared with T0 (0.018 ± 0.006 mg/DW vs. 0.02957 ± 0.0096 mg/DW; P = .01) and T1 (0.0376 ± 0.008 mg/DW; P = .007). Capillary lactates were significantly decreased after 3 weeks, and the mitochondria respiratory rate remained constant over time at the cardia and pylorus, showing significant regional differences. CONCLUSIONS: Manipulation of the gastric flow targeting the gastroepiploic arcade induces ghrelin reduction. An endovascular approach is currently under evaluation.

[The pathophysiology of motor disorders of cardioesophageal transition in children].

The review highlighted some issues on ontogeny of the nervous system of the esophagus. Data on burdened heredity role and gestosis risk of the pregnancy interruption in the development of GERD in childhood are presented. The role of nitrergic and serotoninergic systems and prostaglandins in the development of GERD in children is discussed.

Paradox of gastric cardia: it becomes more acidic following meals while the rest of stomach becomes less acidic.

INTRODUCTION: The proximal cardia region of the stomach has a high incidence of inflammation, metaplasia and neoplasia. It demonstrates less acid buffering following meals than the more distal stomach. Novel high definition pHmetry was employed to investigate acidity at the cardia under fasting conditions and in response to a meal. METHODS: 15 healthy subjects were studied. A custom-made 12-electrode pH catheter was clipped at the squamocolumnar junction with four electrodes recording proximal to and eight distal to the squamocolumnar junction. The most distal pH electrode was located at the catheter tip, and nine electrodes in the region of the squamocolumnar junction were 11 mm apart. RESULTS: The electrode situated in the cardia 5.5 mm distal to the squamocolumnar junction differed from all other intragastric electrodes during fasting in recording minimal acidity (pH <4 = 2.2%) while all other intragastric electrodes recorded high intragastric acidity (pH <4 =or>39%) (p<0.05). The cardia also differed from the rest of the stomach, showing a marked increase in acidity in response to the meal (from 2.2% fasting to 58.4% at 60-70 min after the meal; p<0.05) while the electrodes distal to the cardia all showed a marked decrease in acidity (p<0.05). These changes in acidity at the cardia following the meal caused the gastric acidity to extend 10 mm closer to the squamocolumnar junction. CONCLUSION: Whereas the rest of the stomach shows a marked fall in acidity on ingesting a meal, the cardia paradoxically increases in acidity to become the most acidic region throughout the postprandial period.

Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans.

A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

Effects of potential mediators of an intestinal brake mechanism on gut motility in Chinook salmon (Oncorhynchus tshawytscha).

Potential humoral factors controlling an intestinal brake mechanism in Chinook salmon were characterised in terms of their effect on frequency and amplitude of spontaneous contractions in gastrointestinal (GI) rings. Concentration-response curves of gut contractility were produced for cholecystokinin-8 (CCK-8), gastrin-1, glucagon-like peptide-1 (GLP-1) and 5-hydroxytryptamine (5-HT) using gut rings from cardiac stomach (CS), pyloric stomach (PY), pyloric sphincter (Psp) and intestine (Int). Calculated log10 molar (M) EC50 values for CCK-8 (n=7) were: CS -8.15+/-0.90, PY -7.88+/-0.48, Psp -8.98+/-0.68, Int -8.93+/-0.64. Log10 M EC50 values calculated for gastrin 1 (n=7) were: CS -12.45+/-0.66, PY -12.55+/-0.63, Psp -9.35+/-0.78, Int -12.69+/-1.12. Log10 M EC50 values calculated for 5-HT (n=6) were: CS -4.78+/-1.05 and Psp -6.18+/-1.14. GLP -1 (n=4) produced no response in any of the tissues examined. Spontaneous contractions, measured as spikes per minute and the peak force generated were also measured for each hormone-tissue combination. The Psp generated the greatest mass-specific force, with stomach rings generating the least force. Dilutions of serum from fish diagnosed with gastric dilation air sacculitis (GDAS +ve) increased gut contractility compared to controls (GDAS -ve).

[Comparison of the endoscopic aspect of the cardia, manometry and 24 hours pH measurement in patients with chronic gastroesophageal reflux]. / Comparación entre el aspecto endoscópico del cardias, hallazgos manométricos y pHmetría de 24 horas en pacientes con síntomas de reflujo gastroesofágico crónico.

BACKGROUND: The endoscopic view of the gastric cardia could be related with the manometric competence of the lower esophageal sphincter (LES) and with pathological gastroesophageal reflux. AIM: To compare the endoscopic aspect of the cardia with the results from esophageal manometry and 24 h esophageal pH monitoring. MATERIALS AND METHODS: The cardia of a group of 150 patients (aged 19 to 72 years, 89 women) with gastroesophageal reflux symptoms was classified as normal or open, during upper gastrointestinal endoscopy. All subjects were subjected to a manometric study to measure LES pressure and determine LES incompetence and to a 24 h esophageal pH measurement. RESULTS: LES pressure was 14.7+/-6.2 and 8.7+/-4.2 mmHg in patients with normal and open cardia, respectvively (p <0.001). Likewise, 43 and 79% of patients with normal and open cardia had an incompetent LES, respectively (p <0.001). Pathological acid reflux was present in 43 and 71% of patients with normal or open cardia, respectively (p <0.001). CONCLUSIONS: The endoscopic appearance of the cardia can identify patients with pathological gastroesophageal reflux.

Comparación entre el aspecto endoscópico del cardias, hallazgos manométricos y pHmetría de 24 horas en pacientes con síntomas de reflujo gastroesofágico crónico / Comparison of the endoscopic aspect of the cardia, manometry and 24 hours pH measurement in patients with chronic gastroesophageal reflux

Background: The endoscopic view of the gastric cardia could be related with the manometric competence of the lower esophageal sphincter (LES) and with pathological gastroesophageal reflux. Aim: To compare the endoscopic aspect of the cardia with the results from esophageal manometry and 24 h esophageal pH monitoring. Materials and Methods: The cardia of a group of 150 patients (aged 19 to 72 years, 89 women) with gastroesophageal reflux symptoms was classified as normal or open, during upper gastrointestinal endoscopy. All subjects were subjected to a manometric study to measure LES pressure and determine LES incompetence and to a 24 h esophageal pH measurement. Results: LES pressure was 14.7±6.2 and 8.7±4.2 mmHg in patients with normal and open cardia, respectvively (p <0.001). Likewise, 43 and 79% of patients with normal and open cardia had an incompetent LES, respectively (p <0.001). Pathological acid reflux was present in 43 and 71% of patients with normal or open cardia, respectively (p <0.001). Conclusions: The endoscopic appearance of the cardia can identify patients with pathological gastroesophageal reflux.

Transient lower esophageal sphincter relaxations do not result from passive opening of the cardia by gastric distention.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxation is the main mechanism for gastroesophageal reflux. Although there is evidence that transient lower esophageal sphincter relaxations are neurally mediated, another school of thought is that transient lower esophageal sphincter relaxations result from gastric distention, which shortens the sphincter to the point where it opens and the pressure decreases. We assessed the relationship of transient lower esophageal sphincter relaxation to gastroesophageal junction opening in an unsedated human model. METHODS: Seven healthy volunteers (6 men and 1 woman, aged 18-53 years) were studied while they were sitting. Manometry was performed by using a sleeve catheter passed through 1 nostril. A 5.3-mm endoscope was placed through the other nostril to obtain a retroflexed view of the cardia. The biopsy channel was connected to a barostat to distend the stomach with air at 15 mm Hg for 30 minutes. Manometric and endoscopic video-recording times were synchronized but scored independently. RESULTS: The transient lower esophageal sphincter relaxation onset invariably preceded gastroesophageal junction opening (median, 5.0 seconds; range, 0.5-20.7 seconds; P < .001). The transient lower esophageal sphincter relaxation nadir also typically occurred before gastroesophageal junction opening (median, 2.1 seconds; range, -4.2 to +19.5 seconds; P < .001). Once open, the gastroesophageal junction moved proximally for the duration of the transient lower esophageal sphincter relaxation. Termination of transient lower esophageal sphincter relaxations occurred about the time the time of gastroesophageal junction closure. CONCLUSIONS: These data refute the hypothesis that transient lower esophageal sphincter relaxations result from passive mechanical distraction of the gastroesophageal junction. Rather, transient lower esophageal sphincter relaxations must occur before the gastroesophageal junction can open.

Cells of origin of vagal motor neurons projecting to different parts of the stomach in the rat: confocal laser scanning and electron microscopic study.

Parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) innervate the stomach by way of the gastric and hepatic branches of the vagus nerve. To investigate whether single neurons of the DMV provide collateral innervations to various parts of the stomach, we injected the retrograde tracer Fluoro-Gold (FG) into the cardia and the retrograde tracer cholera toxin subunit b (CTb) into the antrum or the pylorus of the same animal. Both retrogradely FG-labeled and CTb-labeled neurons were found throughout the DMV. Almost all CTb-labeled neurons (97%) were double-labeled with FG after injection of FG into the cardia and CTb into the antrum, while only a few CTb-labeled neurons (11%) were double-labeled with FG after injection of FG into the cardia and CTb into the pylorus. Thus, the cardia and the antrum received collateral projections, but the pylorus received projections mainly from different neurons in the DMV. These results indicate that different neurons in the DMV activate either the cardia or the pyloric sphincter muscles. We also labeled, retrogradely, the neurons projecting to the cardia and the pylorus in the DMV with cholera toxin-conjugated horseradish peroxidase (CT-HRP) to examine their ultrastructural characteristics. Although the neurons projecting to the cardia (21.6x15.0 microm, 248.0 microm2 per section) were significantly smaller than the neurons projecting to the pylorus (27.5x15.9 microm, 323.2 microm2 per section), their ultrastructural appearances were similar. Both types of neurons were small-to-medium sized, round or oval in shape, and generally had a small amount of cytoplasm containing a few Nissl bodies and a round nucleus. The average number of axosomatic terminals per section was low in the neurons projecting to the cardia (2.3) and the neurons projecting to the pylorus (3.0). Almost all axon terminals contacting these motor neurons contained round synaptic vesicles and made asymmetric synaptic contacts (Gray's type I).

Normal patterns of acid exposure at the gastric cardia: a functional midpoint between the esophagus and stomach.

OBJECTIVE: Little is known about the normal anatomical patterns of acid exposure at the gastric cardia and its relationship to acid refluxed into the esophagus. In this study, pH patterns of the gastric cardia at baseline and during esophageal reflux were determined using ambulatory pH monitoring in normal volunteers. METHODS: Ten volunteers with normal distal esophageal acid exposure underwent 18-h ambulatory pH monitoring studies with pH leads placed 5 cm proximal, 5 cm distal, and 10 cm distal to the proximal border of the LES. RESULTS: Median LES length and pressure were 3.5 cm (range 2.5-4.5) and 28 mm Hg (18-48), respectively. Total cardia acid exposure was 45.2% with a wide range (1.0-76.1%) and was significantly different from esophagus (1.6; 0.2-5.9%) and stomach (87.5; 76.0-95.4%) (p < 0.001). Upright (49.8; 1.5-77.0%) and recumbent (31.4; 0-75.1%) cardia acid exposure were not different. Patterns of baseline cardia acid exposure were characterized by: 1) prolonged periods of no acid exposure; 2) isolated brief episodes of acid exposure with stepwise clearances similar to the esophagus; 3) sustained repetitive vacillations between low and neutral pH; or 4) prolonged periods with pH <4 in the cardia. The majority (86.4%) of cardia acid exposures were < 1 min. in duration most consistent with patterns B and C. Esophageal reflux occurred during sustained repetitive vacillations in cardia pH (48%), prolonged periods of cardia acid exposure (33%), or with single transient exposures of acid reflux into the cardia then the esophagus (19%) with stepwise clearance in both. CONCLUSION: 1) Cardia acid exposure is present at a level intermediate between that of the esophagus and stomach; it is most commonly transient but may be continuous, similar to the stomach. 2) Refluxed esophageal acid originates from a pool of acid distal to the cardia that then bathes the cardia in sustained, repetitive, or single acid exposures and occasionally travels into the esophagus.

Motilidades espontânea e estimulada por acetilcolina, de segmentos isolados da cárdia do estômago de cäes, in vitro / Spontaneous and acetylcholine stimulated motility of cardia isolated strips of the stomach of dogs, in vitro

Verificou-se o comportamento motor, espontâneo e estimulado por acetilcolina, de segmentos isolados da cárdia do estômago de caes, "in vitro", utilizando-se banho fisiológico para estudo de órgäos isolados. O estudo teve como objetivo a melhor compreensäo dos fenômenos motores desta regiäo. Para tanto foram utilizados trinta cäes mestiços. Do estômago de cada animal foram retirados segmentos das paredes anterior e posterior, pequena e grande curvaturas. Os tipos de contraçöes encontradas foram: onda I, onda II, onda III, tônicas simples, tônicas segmentares e ondinhas. Foram estudados a amplitude, duraçäo, freqüência e proporçäo de traçados positivos, para cada tipo e regiäo, nos padröes espontâneo e estimulado. Os resultados encontrados mostraram uma proporçäo significante de traçados para as ondas do tipo II no padräo estimulado, em todas as regiöes estudadas. A amplitude das contraçöes tônicas simples diferiram, significantemente, quanto as médias de amplitude na motilidade espontânea, nas quatro regiöes estudadas, sendo que na parede anterior observou-se a maior amplitude média e na parede posterior, a menor. Quanto ao estudo da duraçäo e freqüência, nenhuma diferença significante foi observada. Em conclusäo, a motilidade da cárdia se caracterizou por contraçöes tônicas e peristálticas, representadas, respectivamente, pelas contraçöes tônicas simples e pelas ondas do tipo II.

[Monitoring of the permeability of the inferior esophageal sphincter using sound signals]. / Contrôle de la perméabilité du sphincter oesophagien inférieur á l'aide de signaux sonores.

An original method is described for graphic display of sounds arising from the cardia during the swallowing of saliva or water. Two dynamic microphones were placed on the skin of epigastric xyphoid area and simultaneously on the latero-cervical position. The following conditions must be filled: position of the subject (upright or lying), correct application of microphone with pressure (2 kPa), specially for the xyphoid situation. For graphic restitutions from magnetic signal, a time-recording paper was used, on line or off line, with an analogical device including Butterworth band active filter (optimal frequency range 0.8-1.2 kHz), amplifier and integrator (tau = 2 s). Occurrence of typical cardia sounds were 86-97 % for saliva and 95-100 % for water in two normal subjects for the evaluation of reproducibility (one man and one woman 35 and 47 years old respectively, n = 234 sequences, interval 20 s). Using the distance between the upper and lower microphones, the esophageal time transit can be measured. The signal was more unconstantly recorded for saliva 40 +/- 44 % in adults (n = 10) and 76 +/- 17 % in children (n = 7), than for 80 et 87 % for water respectively. The optimal interval between two swallows appeared to be 15-25 s. In patients with presumption of achalasia (n = 8), the two phonic signals were recorded during esophageal pressure measurement. The presence of esophageal sounds seems to be the sign of absence of achalasia.

Three-dimensional pressure image and muscular structure of the human lower esophageal sphincter.

BACKGROUND: The structural equivalent to the manometric high pressure zone separating the stomach from the esophagus is still a matter of dispute. We compared the three-dimensional (3D) manometric pressure image with muscular thickness and architecture at the human gastroesophageal junction. METHODS: Three-dimensional manometric images were obtained in 25 volunteers by using a stepwise pullback technique of a catheter with eight radially oriented pressure transducers. Muscle thickness was measured in four radial directions at 10 levels between the midesophagus and stomach in 37 specimens obtained from organ donors. Muscular architecture was assessed in specimens from 10 organ donors and 12 human cadavers and was related to muscle thickness. RESULTS: Manometric 3D images of the lower esophageal high pressure zone showed a marked radial and longitudinal asymmetry. Radial pressures peaked at the respiratory inversion point and were highest toward the left posterior direction. Anatomic evaluation showed an asymmetric thickening of the muscular layer at the gastroesophageal junction that mirrored the manometric image. Muscle thickness was highest toward the greater curvature side corresponding to the gastric "sling" fibers and toward the lesser curvature corresponding to the semicircular "clasp" fibers. CONCLUSIONS: The human lower esophageal sphincter is not a muscular ring. Rather, the perfect match between the manometric pressures and the arrangement of muscular structures at the gastroesophageal junction indicates that the gastric sling fibers and the semicircular clasps are the anatomic correlate of the manometric lower esophageal sphincter in human beings.

[X-ray VTR analysis for the inflowing movement of the contrast medium in the esophagocardiac region: the inflowing movement of contrast medium on healthy people].

The application of S-VHS video system has made it possible to easily detect the functional disease. Among several position, left posterior prone position where gravitational force could be ignored, and spontaneous, physiological movement could be registered in the recording of the esophagocardiac movement. Through the observation and the classification of the movement at this position, we evaluated the contribution of this method to the assessment, and the study of the functional diseases such as achalasia, hiatus hernia, and the study of the organic diseases such as carcinoma. In our present study on normal 60 cases, the time from the inflowing first phase to the inflowing interrupted phase in the last period becomes longer as the age of the subjects gets older. The continuous contractive period was divided into three types, shorter type, medium type and longer type. The shorter type seems to correspond to the type closer to hernia. The longer type is regarded as the type closer to achalasia.

Role of the proximal and distal stomach in mixed solid and liquid meal emptying.

The role of the proximal and distal stomach in the emptying of solids and liquids from the stomach remains unclear. We have used a dual isotope technique to quantify proximal and distal stomach emptying of a solid (100 g of 99mTc labelled liver/ground beef) liquid (either 200 ml of normal saline (eight subjects) or 25% dextrose (seven subjects) labelled with 113mIn-diethylenetriaminepenta-acetic acid) mixed meal. A manometric catheter simultaneously measured antral, pyloric, and duodenal motor activity. The liquid component dispersed rapidly throughout the stomach and emptied after a minimal lag period. The emptying of the 25% dextrose was delayed compared with the saline. This delay was associated with increased retention of the liquid in the distal stomach, a significant increase in localised phasic pyloric contractions, and a suppression of antral contractions. The solid component initially resided wholly within a proximal stomach reservoir area. Solids then redistributed from proximal to distal stomach during the emptying of liquid from the stomach. Dextrose delayed gastric emptying of solids compared with saline by increasing the solid lag period and retention in the proximal stomach. There was no significant difference between saline and dextrose meals in the distal stomach retention of solid or in the linear rate of emptying after the lag period. We conclude that, contrary to general opinion, the proximal stomach plays an important role in the control of gastric emptying of solids while the distal stomach is important in the emptying of nutrient liquids.

A laser-induced scar at the cardia increases the yield pressure of the lower esophageal sphincter.

Low yield pressure of the lower esophageal sphincter is associated with esophageal reflux, and fundoplication must increase yield pressure if it is to prevent reflux. We attempted to increase yield pressure endoscopically in the dog by using the Nd:YAG laser to produce a fibrous scar at the cardia in the approximate line of the gastric sling fibers. Ten beagle dogs were studied. In a pilot study with two dogs, 15 watts for 4.2 sec were found to produce a scar deep into the muscle coat of the stomach. Three configurations of scar were used. One produced significant rises in yield pressure in all four of the dogs treated, the second produced a significant rise in one of the two dogs treated, and the third caused a significant drop in yield pressure in the one dog treated. One dog died of gastric perforation 10 days after lasering, but no other animal experienced any ill effects. These findings may have therapeutic implications for the management of esophageal reflux.

Length of the distal esophageal sphincter and competency of the cardia.

Pressure and abdominal length of the distal esophageal sphincter are important factors in maintaining competency of the cardia against challenges of intraabdominal pressure. Some patients with normal distal esophageal sphincter pressure and position may have reflux which could be due to the inability of the cardia to overcome challenges of intragastric pressure. Three experimental studies and one clinical study were designed to evaluate this problem. The results showed that the resistance to flow through the cardia is related to the integrated effect of distal esophageal sphincter pressure and length; the ratio of distal esophageal sphincter to intragastric pressure necessary to maintain competency is inversely related to the length of sphincter present; gastric dilatation has an adverse effect on the degree of competency achieved by a given distal esophageal sphincter length; and patients with an overall distal esophageal sphincter length of 2 cm or less measured at rest in the fasting state are subject to reflux caused by gastric dilatation, increased intragastric pressure independent of intraabdominal pressure, or both.