Mechanism of action of pentagastrin on the lower esophageal sphincter.

The effects of pentagastrin on lower esophageal sphincter (LES) pressure has been studied in trained, unanesthetized dogs. LES pressure was monitored by an infusion manometric technique. Increasing doses of pentagastrin up to 3 mug/kg given as an i.v. bolus resulted in increasing rises in LES pressure; larger doses resulted in a lesser effect of shorter duration. Increasing i.v. boluses of methacholine produced greater increases in LES pressure up to a maximum of 5 mug/kg; higher doses had similar effects. Atropine (50-100 mug/kg) slightly diminished the response of the LES to 2 or 6 mug/kg of pentagastrin. In large doses (500-2,000 mug/kg), atropine did not diminish the response to pentagastrin and prolonged the response of 6 mug/kg pentagastrin. Hexamethonium (2 mg/kg i.v.) depressed the peak response to 3 mug/kg pentagastrin slightly but the response to 6 mug/kg was increased and prolonged. Propranolol (2 mg/kg i.v.) significantly prolonged the effect of 6 mug/kg pentagastrin on the LES. We conclude that the stimulatory effect of pentagastrin is mainly due to a direct action on the LES. A lesser stimulatory effect is due to an action on preganglionic cholinergic neurons. Large doses of pentagastrin have both stimulatory and inhibitory effects. The inhibitory effect is mediated at least in part via preganglionic neurons acting through adrenergic receptors. Ganglionic transmission of the effect may be through muscarinic as well as nicotinic receptors.

Nonlinear adaptive noise compensation in electrogastrograms recorded from healthy dogs.

Adaptive noise compensation is a popular method for improving signal-to-noise ratio in a variety of biomedical applications with its major disadvantage being the requirement for a reference channel containing noise strongly correlated to the noise in the primary channel. In many biomedical applications the utilization of a channel containing such noise without any representation of the information signal is difficult if not impossible. In this study we investigated the possibility of applying adaptive compensation in nonideal noise environments containing substantial presence of information signal in the reference channel. The signal in the reference channel was subjected to nonlinear manipulations for reducing the signal-to-noise ratio, thus diminishing the representation of information signal. The methodology was tested on canine electrogastrographic (EGG) signals of four unconscious dogs which underwent laparotomy and implantation of six pairs internal stainless steel electrodes in addition to the eight-channel abdominal EGG. Fourteen-channel (six internal and eight cutaneous) were obtained from each dog for 1/2 h. The signals were digitized and processed by computer. All internal signals showed regular and coupled gastric electrical activity with frequency of repetition in the normogastric range [3-9 cycles-per-minute (cpm)]. A single pair of primary and reference channels was selected from each cutaneous recording and exponential manipulators in the reference channels were introduced. The manipulators were tuned to maximize the percent distribution of spectral components in the canine normogastric range of each frequency spectrum calculated from the signal at the output of the adaptive compensator. Significant increment in the percent distributions in the normogastric range (p < 0.01) was noted after tuning the exponential manipulator, and in many frequency spectra the recovery of the genuine dominant frequency peak of gastric electrical activity as determined by the internal recordings was noted. This study indicated that low percent distributions registered by some EGG channels are related to external nonlinear factors, the impact of which can be partially compensated.

An active feedback system for isotonic studies of smooth muscle.

A feedback system used to perform isotonic studies of smooth muscle is presented. This system is capable of applying a constant force to muscle samples regardless of their contractile activities. The force applied to the tissue is controlled using a proportional integral control system that drives a linear motor. The device is integrated into a sucrose gap tissue bath apparatus where measurements of displacement and electrical activity are also possible. The frequency of canine colonic smooth-muscle electrical oscillations is positively related to applied force.

A model of gastric electrical activity in health and disease.

The idea of diagnosing gastric dysfunction from noninvasive measurements of gastric electrical activity (GEA) is intuitively appealing, but the predictive accuracy of the cutaneous signal, especially that of its amplitude, is still in question. Mathematical modeling provides a means of investigating, analyzing, and predicting GEA measured percutaneously. In this study, a model of GEA applicable both in health and disease was developed and simulated for a cylindrical body surface. Body-surface maps of the simulated electrogastrogram (EGG) were generated at a 20 by 20 array of sites on the model's surface, and the accuracy of the percutaneous method in detecting simulated gastric electrical abnormalities was determined. The relationship between the amplitude of the simulated surface EGG and the velocity of propagation of the myogenic activity was also investigated. This was compared to a similar investigation of the fluctuations in the amplitude of the surface EGG with the velocity of propagation of the serosal activity measured in humans. The diagnostic accuracy of the measured cutaneous EGG in humans was also determined. The results obtained from the mathematical model show that the amplitude of the electrogastrogram increases with the propagation velocity of GEA. Similar results were obtained from the experimental measurements. The amplitude of the simulated and measured cutaneous signal correlated well (p < 0.05) with the phase shift of the simulated and measured activities, (-0.85, -0.54), respectively. Serosal normal activity, tachygastria, and uncoupling were detected 67%, 90%, and 0% of the time, respectively, at the cutaneous electrode in humans. In simulations, normal activity and tachygastria were accurately detected at all 400 sites on the surface. Uncoupling simulated with 50% of the myogenic sources "diseased" was detected at only 20 of the 400 sites. The results confirm that the amplitude of the cutaneous signal is a function of the velocity of propagation of the myogenic signal. It also confirms that while GEA in health may be accurately predicted from percutaneous recordings, frequency and phase/coupling abnormalities are poorly detected from single-channel electrogastrograms. This suggests the use of multiple-channel surface recordings in clinical electrogastrography.

Reliability of percent distribution of power of the electrogastrogram in recognizing gastric electrical uncoupling.

The aim of this study was to examine the reliability of percent distribution of electrogastrographic (EGG) power in recognizing gastric electrical uncoupling. Sixteen anaesthetized dogs underwent laparotomy and implantation of six pairs of stainless-steel wire electrodes. Distal stomach was measured and three sections with approximately equal lengths were defined. Two pairs of electrodes were implanted in each section. Eight-channel EGG was also recorded. Three separate half-hour recordings were made: in the basal state; after a full circumferential separation of the distal antral section from the rest; after a second circumferential cut completely separating the middle from the proximal sections. EGG digital power spectra were split into three frequency ranges and dynamics of percent distribution of power was statistically examined. After the first cut, changes in the percent distribution of EGG power in the normal range were not significant (p = 0.2). Significant changes in the low range were noted (p < 0.05) and changes in the high range were borderline nonsignificant (p = 0.056). After the second cut, changes in percent distribution in the normal and the high range became significant (p < 0.01) while changes in the low range were insignificant (p = 0.075). Severe uncoupling was reflected in EGG by significant changes in the high-frequency range without internal tachygastria necessarily being present.

Simultaneous measurement of electrical activity from two colonic smooth muscle layers using a dual sucrose gap apparatus.

An apparatus using the sucrose gap technique is presented. With this apparatus simultaneous measurements of contractile and intracellular electrical activity from the two smooth muscle layers of the colon are made. An "L-shaped" muscle preparation consisting of a leg from the circular muscle layer and a leg from the longitudinal muscle layer is used. A theoretical discussion of the device's operation is presented. Finally, experimental results that validate the theory are included.

Electrogastrography: a noninvasive technique to evaluate gastric electrical activity.

Electrogastrography (EGG) is the recording of gastric electrical activity (GEA) from the body surface. The cutaneous signal is low in amplitude and consequently must be amplified considerably. The resultant signal is heavily contaminated with noise, and visual analysis alone of an EGG signal is inadequate. Consequently, EGG recordings require special methodology for acquisition, processing and analysis. Essential components of this methodology involve an adequate system of digital filtering, amplification and analysis, along with minimization of the sources of external noise (random motions of the patient, electrode-skin interface impedance, electrode bending, obesity, etc) and a quantitative interpretation of the recordings. There is a close relationship between GEA and gastric motility. Although it has been demonstrated that EGG satisfactorily reflects internal GEA frequency, there is not acceptable correlation with gastric contractions or gastric emptying. Many attempts have been made to relate EGG 'abnormalities' with clinical syndromes and diseases; however, the diagnostic and clinical value of EGG is still very much in question.

Anorectal manometry in premature infants.

Twenty-eight unselected premature infants were subjected to anorectal pressure studies, using an infusion manometric technique, with a view to establishing normal parameters in this age group. Satisfactory rectal and sphincter pressure readings were obtained in all but one case. In all of these there was a normal anorectal reflex. Low birth weight and prematurity do no preclude a normal anorectal reflex as measured by this technique.

Conoidal dipole model of electrical field produced by the human stomach.

Spontaneous depolarisation and repolarisation due to ionic exchange are the main properties of smooth muscle cells in the human stomach. This change in the distribution of electrical charge results in the creation of an electric field. The field manifests itself as a potential difference (biovoltage), recorded both in vitro and in vivo and known as gastric electrical activity (GEA). The aim of the paper is to describe a computer model of this electric phenomenon, considering all anatomical and electrophysiological particularities of the stomach, and to simulate real in vivo experiments with a computer. In the proposed model, the depolarised smooth muscle cells are represented as organised electrical dipoles distributed with known density in an annular band that moves distally with increasing velocity. Computer simulations of in vivo experiments using this model not only give the waveform, duration, amplitude and frequency of GEA, but they also represent the phase lag between different channels, the difference in propagation velocity along greater and lesser curvatures, and the electric coupling between different parts of the stomach. The effects of changed electrode configuration, surface area and distance from the stomach are described. Mathematical modelling is done in spherical co-ordinates, and the simulations are performed in a specially designed user-friendly IBM PC environment. Some of the unsolved problems in cutaneous electrogastrography are also discussed.

Extracting quantitative information from digital electrogastrograms.

Cutaneous recordings of gastric electrical activity (electrogastrography (EGG)) could become a valuable non-invasive tool for recognising gastric electrical abnormalities. Although signals obtained with internally implanted electrodes deliver quantitative information, this technique cannot be used for diagnostic purposes because of its invasive nature. On the other hand, the objectivity of electrogastrography is still in question. The aims of this work are to develop computer techniques for extracting quantitative information from digital electrogastrograms, and to evaluate quantitatively EGG recordings from healthy volunteers. The dynamics of all four EGG parameters are studied: amplitude, frequency, time shift between different channels, and waveform. Four separate two-dimensional computer plots are developed using specially designed digital signal-processing procedures. Each parameter is evaluated in a study of 20 healthy volunteers. Frequency is found to be the only EGG parameter that shows quantitative consistency and merit.

Computer simulation of the impact of different dimensions of the stomach on the validity of electrogastrograms.

The impact of the dimensions of the stomach on cutaneous recordings of gastric electrical activity (GEA) has not been adequately studied. The stomach was represented as a truncated conoid in a spherical coordinate system. The gastric electric field was modelled using a previously described methodology. Electrical potentials were calculated from sets of points simulating standard cutaneous recordings. The frequency of the signals was maintained at 3 cycles min-1 (period of repetition: 20 s), while the velocity of propagation of the depolarisation waves was reduced relative to the reduction in gastric dimensions. The signals were digitally contaminated with a random artificial artefact with a constant amplitude range of 0.2 mV, while the dimensions of the conoid (the circumferential radii and the length of the central axis) were decreased by factors of 1.5, two, four, six and eight. Simulated EGG signals were evaluated quantitatively. Simulated EGG records contaminated with random signals recorded from stomachs with decreasing dimensions exhibited non-linearly increasing standard deviations (p < 0.001). Randomly contaminated EGGs calculated from stomachs with dimensions reduced four, six and eight times were abnormal according to previously established quantitative criteria. Computer modelling indicated that gastric dimensions can significantly influence the validity of EGGs. These findings could be particularly important in a paediatric electrogastrography.

Comparative quantification of gastric electrical activity and electrogastrograms.

The aim of this study was to compare quantitatively the variability of gastric electrical activity (GEA) recorded from asymptomatic patients with implanted serosal electrodes and patients with implanted and cutaneous electrodes. Three pairs of electrodes were inserted into the gastric wall in six patients undergoing laparotomy for other reasons. Normal GEA was assessed visually once patients were tolerating a normal diet. Mean frequency (MF) values of the GEA signal in successive 256 s intervals were obtained. Standard deviations of the MF values for each separate channel of each patient were calculated. Probability density functions (pdfs) of these values were also obtained and compared. 36 1 h simultaneous recordings were made for three patients with implanted and cutaneous electrodes. The recordings were assessed both visually and with computer. A fast Hartley transform was used to obtain the dominant MF values in 256 s time intervals. These values were statistically evaluated for each channel. Normal internal GEA had a mean frequency of 2.5-3.75 cycles min-1 (cpm) and a standard deviation range of 0-0.45 cpm. Bell-shaped pdfs with coinciding maxima were observed in all these recordings, indicating normal electrical coupling. In the comparative 36 h study, using the above definitions of normality, different cutaneous recordings were found to reflect GEA with a sensitivity of 94% and a specificity of 79%.

Application of an object-oriented programming paradigm in three-dimensional computer modeling of mechanically active gastrointestinal tissues.

The aim of this study was to develop a novel three-dimensional (3-D) object-oriented modeling approach incorporating knowledge of the anatomy, electrophysiology, and mechanics of externally stimulated excitable gastrointestinal (GI) tissues and emphasizing the "stimulus-response" principle of extracting the modeling parameters. The modeling method used clusters of class hierarchies representing GI tissues from three perspectives: 1) anatomical; 2) electrophysiological; and 3) mechanical. We elaborated on the first four phases of the object-oriented system development life-cycle: 1) analysis; 2) design; 3) implementation; and 4) testing. Generalized cylinders were used for the implementation of 3-D tissue objects modeling the cecum, the descending colon, and the colonic circular smooth muscle tissue. The model was tested using external neural electrical tissue excitation of the descending colon with virtual implanted electrodes and the stimulating current density distributions over the modeled surfaces were calculated. Finally, the tissue deformations invoked by electrical stimulation were estimated and represented by a mesh-surface visualization technique.

Dynamics of the level of deterministic chaos associated with gastric electrical uncoupling in dogs.

This study investigated the impact of gastric electrical uncoupling on the dynamics of the level of deterministic chaos in cutaneous gastric electrical signals. Eight-channel electrogastrograms (EGG) were recorded from 16 unconscious dogs. Controlled gastric electrical uncoupling was introduced by circumferentially cutting the whole gastric muscle at two different locations. Three separate 30-min EGG recordings were obtained from each dog in the three different states (basal, after the first cut, and after the second cut). The Lyapunov exponents were calculated from sixteen 6.31-min intervals with 75% overlap obtained from each channel in each state. Inadequate EGG signals from which the Lyapunov exponent could not be reliably calculated were quantitatively discarded. The variance and the standard deviation of the three Lyapunov exponent distributions obtained from each channel were studied, and the mean values were subjected to a Student t-test. In 65.6% of all studied channels, the level of chaos was significantly different (p< 0.01) after the first cut compared to the basal state, but no predominant direction of variation was observed (47. 7% increment vs. 52.5% decrement). After the second cut, 63.6% of the channels studied showed significantly greater Lyapunov exponent compared to the basal state, and 63.1% exhibited significantly greater (p< 0.01) level of chaos compared to the intercut state. The dynamics of the level of deterministic chaos in canine electrogastrograms is highly sensitive to severe gastric electrical uncoupling. Moreover, some channel configurations seem to be more sensitive than others in detecting uncoupling.

Computer simulation of the effect of changing abdominal thickness on the electrogastrogram.

The effect of different abdominal thickness on cutaneous recordings of gastric electrical activity (GEA) known as electrogastrograms (EGG) have not been adequately studied. The stomach was represented as a truncated conoid in spherical system of coordinates. Gastric electrical field was modelled using previously described methodology. Electrical voltages were calculated in simulated standard cutaneous recordings. The effect of increased thickness of the abdominal layers was quantitatively examined. Changes of the thickness of the abdominal layers significantly affected signal-to-noise ratio of EGG. When the critical abdominal thickness of 7 cm was exceeded, EGGs were quantified as abnormal although the internal GEA was normal. Computer modelling indicated that changeable abdominal thickness caused by the abdominal layers separating the stomach from the recording electrodes significantly influence the EGG recordings even if the layers are homogeneous.

Electrogastrographic impact of multi-site functional gastric electrical stimulation.

Microprocessor-controlled multi-site functional gastric electrical stimulation using synchronized higher frequency (above 25 Hz) bipolar voltages has been suggested as a possible new avenue towards efficient artificial control of gastric motility. However, the effect of this sequential stimulation on gastric electrical activity is unknown. Because of the substantial strength of the invoked sequential contractions, using implanted electrodes to assess gastric electrical activity (GEA) in experimental animals is difficult, if not impossible. Electrogastrography (EGG), the non-invasively obtained recording of GEA, provides an excellent opportunity to study the changes associated with the multi-site functional stimulation. In this study, we investigated 4 unconscious dogs with 4 circumferential sets of subserosally-implanted stimulating electrodes and 4 force transducers attached close to each stimulating electrode set at operation. The abdominal cavity of each dog was closed after the electrode implantations and 3 standard neonatal electrocardiographic electrodes were attached overlying the abdominal projection of the gastric axis. Two-channel EGG recordings were obtained for 1/2 h before any electrical stimulation and during 1/2 h of intensive sequential stimulation. Significant changes were observed in the EGG pattern during stimulation. These changes were quantified and compared to the basal recordings. Our findings indicate that the interrelation between spectral changes in cutaneous EGG and mechanical activity of the stomach could be far more complex than previously speculated.

Three-dimensional static parametric modelling of phasic colonic contractions for the purpose of microprocessor-controlled functional stimulation.

The study aimed at creating an integrated electromechanical model of invoked phasic contractions in canine colon during direct high frequency voltage stimulation. The model utilized data obtained from two large anaesthetized dogs that underwent laparotomy and serosal implantation of two circumferential electrode pairs into a distal segment of the left colon. The strength distribution of the stimulating electric field was analysed over a cylindrical mesh-surface grid modelling the interrogated colonic segment. Recordings of the stimulating current were utilized to model smooth muscle depolarization using linearized macroscopic tissue conductivity. The invoked contractile stress was related to the stimulating electric field strength using an exponential sigmoid function. Artificially produced occlusion of the lumen was derived for a pair of 5mm electrodes positioned on a cylindrical mesh-surface of 2 cm diameter and 15 cm length. The model simulated contractions invoked by stimuli of different amplitude (up to 12 V) with 98.6% accuracy of approximation. Macroscopic tissue conductivity was modelled as a combination of two first-order exponential terms involving a 3ms time constant. Real-time simulation of the current drawn by the smooth muscle during 10 V/50Hz bipolar voltage stimulation was performed. The integrated electromechanical model facilitates the quantification of microprocessor-controlled phasic colonic contractions.