Biomedical subjects

James G Brasseur

Publications and source records attributed to James G Brasseur.

11 recordsLinked to original sources

PubMed2005

Physiology of the esophageal pressure transition zone: separate contraction waves above and below.

Manometrically measured peristaltic pressure amplitude displays a well-defined trough in the upper esophagus. Whereas this manometric "transition zone" (TZ) has been associated with striated-to-smooth muscle fiber transition, the underlying physiology of the TZ and its role in bolus transport are unclear. A computer model study of bolus retention in the TZ showed discoordinated distinct contraction waves above and below. Our aim was to test the hypothesis that distinct upper/lower contraction waves above/below the manometric TZ are normal physiology and to quantify space-time coordination between tone and bolus transport through the TZ. Eighteen normal barium swallows were analyzed in 6 subjects with concurrent 21-channel high-resolution manometry and digital fluoroscopy. From manometry, the TZ center (nadir pressure amplitude) and the upper/lower margins of the pressure trough were objectively quantified. Using fluoroscopy, we quantified space-time trajectories of the bolus tail and bolus tail pressures and maximum intraluminal pressures proximal to the tail with their space-time trajectories. In every swallow, the bolus tail followed distinct trajectories above/below the TZ, separated by a well-defined spatial "jump" that terminated an upper contraction wave and initiated a lower contraction wave (3.32 +/- 1.63 cm, P = 0.0004). An "indentation wave" always formed within the TZ distal to the upper wave, increasing in amplitude until the lower wave was initiated. As the upper contraction wave tail entered the TZ, it slowed and the tail pressure reduced rapidly, while indentation wave pressure increased to normal tail pressure values at the initiation of the lower wave. The TZ was a special zone of segmental contraction. The TZ is, physiologically, the transition from an upper contraction wave originating in the proximal striated esophagus to a lower contraction wave that moves into the distal smooth muscle esophagus. Complete bolus transport requires coordination of upper/lower waves and sufficient segmental squeeze to fully clear the bolus from the TZ during the transition period.

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↗

PubMed2005

The mechanical basis of impaired esophageal emptying postfundoplication.

Fundoplication (FP) efficacy is a trade-off between protection against reflux and postoperative dysphagia from the surgically altered mechanical balance within the esophagogastric segment. The purpose of the study was to contrast quantitatively the mechanical balance between normal and post-FP esophageal emptying. Physiological data were combined with mathematical models based on the laws of mechanics. Seven normal controls (NC) and seven post-FP patients underwent concurrent manometry and fluoroscopy. Temporal changes in geometry of the distal bolus cavity and hiatal canal, and cavity-driving pressure were quantified during emptying. Mathematical models were developed to couple cavity pressure to hiatal geometry and esophageal emptying and to determine cavity muscle tone. We found that the average length of the hiatal canal post-FP was twice that of NC; reduction of hiatal radius was not significant. All esophageal emptying events post-FP were incomplete (51% retention); there was no significant difference in the period of emptying between NC and post-FP, and average emptying rates were 40% lower post-FP. The model predicted three distinct phases during esophageal emptying: hiatal opening (phase I), a quasi-steady period (phase II), and final emptying (phase III). A rapid increase in muscle tone and driving pressure forced normal hiatal opening. Post-FP there was a severe impairment of cavity muscle tone causing deficient hiatal opening and flow and bolus retention. We conclude that impaired esophageal emptying post-FP follows from the inability of distal esophageal muscle to generate necessary tone rapidly. Immobilization of the intrinsic sphincter by the surgical procedure may contribute to this deficiency, impaired emptying, and possibly, dysphagia.

Adult↗

PubMed2005

Restoration of normal distensive characteristics of the esophagogastric junction after fundoplication.

OBJECTIVE: To study the mechanical characteristics of the esophagogastric junction (EGJ) of postfundoplication patients and compare them with previously reported data on normal subjects and GERD patients. METHODS: Eight normal subjects, 9 GERD patients, and 8 fundoplication patients were studied with concurrent manometry, fluoroscopy, and stepwise controlled barostat distention of the EGJ. The minimal barostat pressure required to open the EGJ during the interswallow period was determined. Thereafter, barium swallows were imaged in 5-mm Hg increments of intrabag pressure. EGJ diameter and length were measured at each pressure during deglutitive relaxation. RESULTS: EGJ opening diameter during deglutitive relaxation was on average 0.5 cm greater in GERD patients compared with normal subjects and fundoplication patients (P < 0.05). EGJ opening pressure and opening diameter were comparable between normal subjects and fundoplication patients; however, the EGJ length was 32% longer in fundoplication patients. CONCLUSIONS: Fundoplication restores distensibility of the EGJ to a level similar to normal subjects. Since trans-EGJ flow is related to EGJ length and EGJ diameter, these findings suggest that retrograde flow through the EGJ would be decreased by both a reduction in diameter and an increase in length of the EGJ.

Adult↗

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↗

PubMed2004

Mechanics and hemodynamics of esophageal varices during peristaltic contraction.

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.

Adult↗

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↗

PubMed2003

Volume (3-dimensional) space-time reconstruction of esophageal peristaltic contraction by using simultaneous US and manometry.

BACKGROUND: Conventional 3-dimensional endoluminal US was modified to evaluate peristaltic contractions in the esophagus. METHODS: Two-dimensional US images and simultaneous intraluminal pressures were acquired during peristaltic contractions by locating the transducer at fixed positions in the esophagus in 6 normal volunteers during swallowing. Three-dimensional images were reconstructed by using a computer-based 3-dimensional algorithm with time as the x axis. RESULTS: The peristaltic contraction sequence was viewed as a 3-dimensional US image. The geometric configuration of the esophagus, the muscle thickness, and corresponding pressures were evaluated. The 3-dimensional images demonstrate 4 phases of the peristaltic contraction sequence. CONCLUSIONS: Three-dimensional time-resolved reconstruction of endoluminal US images of the esophagus and simultaneous recording of manometric data allow visualization of geometric changes and correlation with pressure changes during peristaltic contraction. Four phases of the peristaltic contraction sequence are demonstrated clearly on the 3-dimensional space-time images.

Adult↗

PubMed2002

A mathematical model for estimating muscle tension in vivo during esophageal bolus transport.

We present a model of esophageal wall muscle mechanics during bolus transport with which the active and "passive" components of circular muscle tension are separately extracted from concurrent manometric and videofluoroscopic data. Local differential equations of motion are integrated across the esophageal wall to yield global equations of equilibrium which relate total tension within the esophageal wall to intraluminal pressure and wall geometry. To quantify the "passive" (i.e. inactive) length-tension relationships, the model equations are applied to a region of the esophagus in which active muscle contraction is physiologically inhibited. Combining the global equations with space-time-resolved intraluminal pressure measured manometrically and videofluoroscopic geometry data, the passive model is used to separate active and "passive" components of esophageal muscle tension during bolus transport. The model is of general applicability to probe basic muscle mechanics including the space-time stimulation of circular muscle, the relationship between longitudinal muscle tension and longitudinal muscle shortening, and the contribution of the collagen matrix surrounding muscle fibers to passive tension during normal human esophageal bolus transport and in pathology. Example calculations of normal esophageal function are given where active tone is found to extend only over a short intrabolus segment near the bolus tail and segmental regions of active muscle squeeze are demonstrated.

Biomechanical Phenomena↗

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↗

PubMed2002

Esophagogastric junction distensibility: a factor contributing to sphincter incompetence.

To quantify the effect of hiatus hernia (HH) on esophagogastric junction (EGJ) distensibility, eight normal subjects and nine gastroesophageal reflux disease (GERD) patients with HH were studied with concurrent manometry, fluoroscopy, and stepwise controlled barostatic distention of the EGJ. The minimal barostatic pressure required to open the EGJ during the interswallow period was determined. Thereafter, barium swallows were imaged in 5-mmHg increments of intrabag pressure. EGJ diameter and length were measured at each pressure during deglutitive relaxation. The EGJ opening diameter was greater in hernia patients compared with normal subjects during deglutitive relaxation at all pressures, and EGJ length was 23% shorter. EGJ opening pressure among hernia patients was lower than normal subjects during the interswallow period. In conclusion, the EGJ of GERD patients with HH was more distensible and shorter than normal subjects. These findings partially explain why HH patients are predisposed to reflux by mechanisms other than transient lower esophageal sphincter relaxations, sustain greater volumes of refluxate, and have a reduced ability to discriminate gas from liquid reflux.

Adult↗