Anupam Pal

Gastric flow and mixing studied using computer simulation

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High–resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two–dimensional computer model of the stomach was developed with the ‘lattice–Boltzmann’ numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde ‘jets’ through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well–defined ‘zone of mixing’, confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction–induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.

Quantification of distal antral contractile motility in healthy human stomach with magnetic resonance imaging.

To quantify healthy postprandial: 1) propagation, periodicity, geometry, and percentage occlusion by distal antral contraction waves (ACWs); and 2) changes in ACW activity in relationship to gastric emptying (GE).

The mechanical advantage of local longitudinal shortening on peristaltic transport.

Whereas bolus transport along the esophagus results from peristaltic contractions of the circular muscle layer, it has been suggested that local shortening of the longitudinal muscle layer concentrates circular muscle fibers in the region where the highest contractile pressures are required. Here we analyze the mechanical consequences of local longitudinal shortening (LLS) through a mathematical model based on lubrication theory. We find that local pressure and shear stress in the contraction zone are greatly reduced by the existence of LLS. In consequence, peak contractile pressure is reduced by nearly 2/3 at physiological LLS, and this reduction is greatest when peak in LLS is well aligned with peak contractile pressure. We conclude that a peristaltic wave of local longitudinal muscle contraction coordinated with the circular muscle contraction wave has both a great physiological advantage (concentrating circular muscle fibers), and a great mechanical advantage (reducing the level of contractile force required to transport the bolus), which combine to greatly reduce circular muscle tone during esophageal peristalsis.

Abnormal Structure and Function of the Esophagogastric Junction and Proximal Stomach in Gastroesophageal Reflux Disease

OBJECTIVES:This study applies concurrent magnetic resonance imaging (MRI) and high-resolution manometry (HRM) to test the hypothesis that structural factors involved in reflux protection, in particular, the acute insertion angle of the esophagus into the stomach, are impaired in gastroesophageal reflux disease (GERD) patients.METHODS:A total of 24 healthy volunteers and 24 patients with mild-moderate GERD ingested a test meal. Three-dimensional models of the esophagogastric junction (EGJ) were reconstructed from MRI images. Measurements of the esophagogastric insertion angle, gastric orientation, and volume change were obtained. Esophageal function was assessed by HRM. Number of reflux events and EGJ opening during reflux events were assessed by HRM and cine-MRI. Statistical analysis applied mixed-effects modeling.RESULTS:The esophagogastric insertion angle was wider in GERD patients than in healthy subjects (+7°±3°; P=0.03). EGJ opening during reflux events was greater in GERD patients than in healthy subjects (19.3 mm vs. 16.8 mm; P=0.04). The position of insertion and gastric orientation within the abdomen were also altered (both P<0.05). Median number of reflux events was 3 (95% CI: 2.5–4.6) in GERD and 2 (95% CI: 1.8–3.3) in healthy subjects (P=0.09). Lower esophageal sphincter (LES) pressure was lower (−11±2 mm Hg; P<0.0001) and intra-abdominal LES length was shorter (−1.0±0.3 cm, P<0.0006) in GERD patients.CONCLUSIONS:GERD patients have a wider esophagogastric insertion angle and have altered gastric morphology; structural changes that could compromise reflux protection by the “flap valve” mechanism. In addition, the EGJ opens wider during reflux in GERD patients than in healthy volunteers: an effect that facilitates volume reflux of gastric contents.

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study.

Abstract  Gastric emptying (GE) may be driven by tonic contraction of the stomach (‘pressure pump’) or antral contraction waves (ACW) (‘peristaltic pump’). The mechanism underlying GE was studied by contrasting the effects of clonidine (α2‐adrenergic agonist) and sumatriptan (5‐HT1 agonist) on gastric function. Magnetic resonance imaging provided non‐invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min−1 IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r2 = 49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r2 = 15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the ‘pressure pump’ mechanism.

96 The Structure and Function of the Gastro-Esophageal Junction in Health and Reflux Disease Assessed By Magnetic Resonance Imaging and High Resolution Manometry

nitrate, and during acid reflux, generation of NO is shifted to the distal esophagus. We have demonstrated that high concentrations of luminal NO can impair the gastric mucosal barrier function by disrupting the tight junction (Gut 2008). We hypothesized that NO generated luminally during acid reflux could disrupt the esophageal barrier function and provoke DIS. Aim: To investigate the direct effects of luminal NO on the esophageal barrier function using an ex vivo chamber model. Design and Setting: A chamber model in which the rat esophageal mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the esophagus. On the mucosal side of the chamber, NO was generated by the acidification of physiologic concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance (R) and membrane permeability with 3H-mannitol flux in four groups; Krebs buffer, acid alone (pH 1.5), acid + sodium nitrite 5.0 mM, and acid + sodium nitrite 1.0 mM. Intercellular space diameters were measured on transmission electron microscopy photomicrographs. Results: In all groups except for Krebs buffer, the R decreased rapidly within the initial 15 minutes, followed by gradual decrease thereafter. At 180 minutes, the R decreased by 34% in acid alone group, by 39% in acid + nitrite 1.0 mM group, by 45% in acid + nitrite 5.0 mM group by 55%. Consequently, the administration of acidified nitrite (1.0 mM or 5.0 mM) to the mucosal side significantly decreased the R compared with that of the acid alone (p<0.01). While epithelial permeability with 3Hmannitol slightly increased at 180 minutes in acid alone group, it remarkably increased in acid + nitrite 5.0 mM group. Thus, the administration of acidified nitrite to the mucosal side significantly increased epithelial permeability compared with the acid alone group (p<0.05). DIS was observed in the nitrite groups but not in the acid alone group. Conclusions: The NO generated luminally via acidification of nitrite disrupted the barrier function of the esophageal epithelium and provoked DIS, suggesting that NO generated luminally contributes to DIS observed in GERD patients and plays an important role in the pathophysiology of GERD.