Biomedical subjects

Anupam Pal

Publications and source records attributed to Anupam Pal.

6 recordsLinked to original sources

PubMed2006

A stomach road or "Magenstrasse" for gastric emptying.

Gastric muscle contractions grind and mix solid/liquid meal within the stomach, and move it into the bowels at a controlled rate. Contractions are of two types: slow volume-reducing contractions of the proximal stomach (the fundus), and peristaltic contraction waves in the distal stomach (the antrum). Fundic squeeze maintains gastro-duodenal pressure difference to drive gastric emptying. Emptying is generally assumed to proceed from the antrum to the fundus, so that ingested drugs can take hours to enter the small intestines and activate. Antral contraction waves (ACW), in contrast, generate fluid motions that break down and mix gastric content. Using a computer model of the human stomach, we discover a new function of these contraction waves apart from grinding and mixing. In coordination with fundic contraction, antral contraction waves move liquid content from the fundus along a very narrow path to the duodenum through the center of the antrum. Using physiological data, we show that this gastric emptying "Magenstrasse" (stomach road) can funnel liquid gastric content from the farthest reaches of the fundus directly to the intestines within 10 min. Consequently, whereas drugs (tablets, capsules, liquid) released off the Magenstrasse may require hours to enter the duodenum, at low concentration, when released on the Magenstrasse the drug can enter the duodenum and activate within 10 min-at high concentration. This discovery might explain observed high variability in drug initiation time, and may have important implications to both drug delivery and digestion, as well as to other wall-driven emptying of elastic containers.

Biological Clocks↗

PubMed2006

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

PURPOSE: 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). MATERIALS AND METHODS: Using 1.5-T MR scanner, nine healthy fasted volunteers were examined in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) with 500 microM Gd-DOTA. Total gastric (TGV) and meal volumes (MV) were assessed every five minutes for 90 minutes, in and interspersed with dynamic scan sequences (duration: 2.78 minutes) providing detailed images of distal ACWs. RESULTS: TGV increased by 738+/-38 mL after ingestion (t0), subsequently decreasing in parallel to GE. The mean GE rate and half-emptying time were 24+/-3 mL/5 minutes and 71+/-6 minutes, respectively. Accompanying ACWs reached a periodicity of 23+/-2 seconds at t35 and propagated at an unvarying speed of 0.27+/-0.01 cm/second. Their amplitude of 0.70+/-0.08 cm was constant, but the width decreased along the antral wall by 6+/-2%/cm (P=0.003). ACWs were nonocclusive (percentage occlusion 58.1+/-5.9%, t0 at the pylorus) with a reduction in occlusion away from the pylorus (P<0.001). No propagation and geometry characteristics of ACWs correlated with the changes of MV (mL/5 minutes; R2<0.05). CONCLUSION: Our results indicate that ACWs are not imperative for emptying of liquids. This study provides a detailed quantitative reference for MRI inquiries into pharmacologically- and pathologically-altered gastric motility.

Adult↗

PubMed2005

A novel in vitro and numerical analysis of shear-induced drug release from extended-release tablets in the fed stomach.

PURPOSE: To design an in vitro apparatus that could simulate the in vivo range of surface shear stresses relevant for the human stomach under fed conditions. METHODS: Computer simulations were combined with in vitro experiments to quantify tablet erosion rate vs. surface shear stress. From two separate computer models, of tablets in the fed stomach and of tablets in vitro, we first estimated the intragastric range of surface stress and Reynolds number (Re), and then designed a dissolution apparatus and parameter space to replicate the in vivo conditions. The in vitro tablet erosion was determined by a new rotating beaker apparatus that provided predictable surface shear on tablets. Tablet mass erosion rates were measured for two different extended-release tablets at a range of in vivo relevant surface shear stresses obtained by varying viscosity of test media and rotation rate of the beaker. RESULTS: Mass erosion rate and surface shear were found to be highly correlated. Erosion rate increased with surface shear more rapidly at "low" stresses (<35 dyne/cm2) independent of tablet material. At higher surface stress, erosion was strongly material dependent. CONCLUSIONS: Shear force effects on drug release from matrix tablets relevant for fed state are for the first time possible to predict by in vitro dissolution testing.

Algorithms↗

PubMed2004

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.

Computer Simulation↗

PubMed2003

Intrabolus pressure gradient identifies pathological constriction in the upper esophageal sphincter during flow.

Propulsion of a bolus through the upper esophageal sphincter (UES) is driven by a pressure drop in the direction of flow against frictional resisting force. Basic mechanics suggest that the axial rate of drop in intrabolus pressure (IBP), i.e., the intrabolus pressure gradient (IBPG), should be locally sensitive to abnormal constriction. We sought to quantify space-time patterns of IBP and IBPG that correlate with pathological disruption to transsphincteric bolus transport. High-resolution high-fidelity perfused manometry was applied concurrent with videofluoroscopy in 6 healthy controls and 10 patients with restricted UES opening and 4 bolus volumes. Pressures were interpolated spatially and displayed as space-time isocontours with bolus head and tail trajectories superimposed to identify the IBP domain. IBP and IBPG were averaged over an approximately steady period of transsphincteric flow. The axial location and magnitude of maximum IBPG were quantified for each swallow relative to the location of the abnormal restriction. We found that average hypopharyngeal IBP and locally maximal IBPG were significantly higher in the patient group (P < 0.001), whereas the maximum IBPG was insensitive to bolus volume, and the locations of maximum IBPG in the patient group were well correlated with axial locations of maximal UES constriction (r = 0.84, P < 0.01). Space-time structure of IBP and IBPG correlated qualitatively with swallow dysfunction. Because IBPG reflects pressure force driving the bolus against frictional force in the UES, IBPG reflects local changes in frictional resistance from pathological constriction during bolus flow. Consequently, the location and magnitude of IBPG reflect the existence and location of abnormal constriction, and IBP and IBPG structure reflect decompensation of the pharyngeal swallow.

Adult↗

PubMed2002

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.

Biological Transport↗