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Biomedical subjects

W J Lammers

Publications and source records attributed to W J Lammers.

At least 19 recordsLinked to original sources

Two-dimensional high-resolution motility mapping in the isolated feline duodenum: methodology and initial results.

Several types of electrical events occur in the small intestine but their spatial and temporal contributions to overall motility are not clear. In order to quantify local motility in greater detail, a new technique of recording and analysing movements at multiple sites was developed. Use was made of isolated segments of feline duodenum superfused in a tissue bath. Multiple marker dots (20-75) were placed on the serosal surface by applying fine spots of candle soot in rectangular arrays (1-2 mm dot separation). A digital video camera was used to record spontaneous movements of the dots for periods of 10-30 min. After each experiment, 4-6 periods (10-60 s each) of video frames were transferred to a computer (25 fps, 720 x 576 pixels) and the movements of the dots was tracked every 40 ms using custom-made software. Initial results (eight experiments) show that spontaneous motility is remarkably variable, both in space and time. Three types of movement could be discerned: (i) periodic, rolling or pendular movements, with a frequency of approximately 15 min-1 occurring predominantly in the longitudinal direction; (ii) twitches, wherein a subset of dots were suddenly displaced longitudinally; and (iii) drifts of most of the dots in a circular or oblique direction. All three types of movement occurred throughout every recording session although their relative magnitudes differed greatly from moment to moment. Occasionally, it was possible to detect propagated 'contractions' with an apparent velocity of 10 mm s(-1). Immobilizing the preparation at one point by inserting a needle through the middle of the array of markers had a negligible effect on the displacements, whereas application of verapamil (10(-5) mol L(-1)) reduced or abolished motility. In summary, we present a new technique to map in detail two-dimensional motility at the surface of the intestine. Initial results seem to suggest that motility at the serosal surface is not uniform and highly anisotropic.

Animals↗

Of slow waves and spike patches.

In the small intestines, the major task of the slow wave is to induce mechanical movements in the intestinal wall by generating local calcium spikes. High resolution electrical mapping reveals fundamental differences in propagation between slow waves and calcium spikes. These differences suggest that slow waves and spikes are propagated by different mechanisms through different cell networks.

Action Potentials↗

The spatial behaviour of spike patches in the feline gastroduodenal junction in vitro.

In the isolated feline gastroduodenal region, the spatial propagation of slow waves and of individual spikes was reconstructed. Recordings were performed simultaneously from 240 extracellular electrodes positioned on the serosal surface across the junction. Results from nine experiments (22 slow waves) showed that the slow wave never propagated across the gastroduodenal region and that this block was due to the presence of a zone of quiescence caudal to the pylorus. In contrast, spikes (n=155) were able to propagate into the quiescent zone, either from the antrum (15.4%) or from the duodenum (34.0%) and occasionally, were able to propagate from one organ to the other (10.9%). However, in all cases, spike conduction was self-limited and activated a local area termed a 'patch'. The length of the patches located in the gastroduodenal region was significantly longer than in the rest of the duodenum (20.2 mm +/- 9. 7 vs. 9.5 mm +/- 3.2; P < 0.001) indicating a possible enhancement of spike propagation in this region. In conclusion, in spite of the total conduction block for slow waves, individual spikes are able to propagate across the gastroduodenal region, albeit in self-limited areas or 'patches'. These spike patches could form the building blocks for gastroduodenal coordination.

Action Potentials↗

Propagation of individual spikes as "patches" of activation in isolated feline duodenum.

Asynchrony of spikes has made it difficult to study the spatial and temporal behavior of spikes in the gastrointestinal system. By simultaneously recording from a large number of closely spaced electrodes, we investigated the propagation of individual spikes. Recordings were performed from the serosal surface of the isolated feline duodenum at 240 sites simultaneously. Analysis of the tracings made it possible to reconstruct the propagation of individual spikes. Spikes propagate in the longitudinal and circumferential directions in self-limiting areas or "patches." Conduction within patches may occur in the orad or aborad direction irrespective of the direction of the slow wave. Most of the patches are smaller (<40 mm(2)), although inhomogeneous activation by the preceding slow wave may increase their size. Stimulation by ACh, TTX, or tetraethylammonium does not affect the average patch size but does increase significantly their number and distribution in the duodenum [from 26% (control) to 56%, 61%, and 72%, respectively]. In conclusion, individual spikes activate limited areas or patches in the small intestine, and pharmacological stimulation increases the number and distribution of these patches. In the small intestine, this pattern of activation would induce localized contractions. Contraction could be modulated by the size, number, and distribution of spike patches.

Acetylcholine↗

The effects of oxytocin on the pattern of electrical propagation in the isolated pregnant uterus of the rat.

In the isolated pregnant myometrium of the rat, the pattern of propagation was investigated by recording simultaneously from 240 different extracellular sites while the contraction of the tissue was recorded isometrically. Analysis of all recorded electrograms allowed the two-dimensional spread of activity in the myometrium to be reconstructed. From these activation maps, the conduction velocities were measured in the longitudinal, oblique and transversal directions. At low concentrations (10(-9 )and 5x10(-9) M), oxytocin significantly increased the frequency and duration of electrical bursts and the average spike intervals, without affecting the homogeneity of action potential propagation, concomitant with a significant increase in the amplitude of contractions. At high concentrations (10(-8) and 5x10(-8) M), oxytocin induced conduction blocks and the size of inexcitable areas was increased, concomitantly with an increase in muscle contractures. In contrast, the conduction velocities in the longitudinal, oblique and circular directions were not influenced by oxytocin at any concentrations.

Action Potentials↗

The initiation, continuation, and termination of spontaneous episodes of circus movements in the pregnant myometrium of the rat.

OBJECTIVES: The objectives of this study were to determine the mechanisms responsible for the initiation and the termination of episodes of circus movements and to describe the characteristics of these circuits in rat myometrium. STUDY DESIGN: By means of simultaneous recordings from 240 sites in Wistar rats at 17, 19, or 21 days' gestation, a spatial and temporal analysis was performed on the electrical activation from the beginning until the end of 22 episodes of circus movements. RESULTS: The initiation of reentry was caused by (1) transient unexcitable areas at the beginning of the burst or (2) lines of conduction blocks. Circus movements were terminated by (1) reversal of recruitment (decruitment) at the end of the burst, (2) occurrence of lines of conduction blocks, or (3) interruption of the circuit. On average circuits rotated for 6 revolutions during 2 seconds. In most cases circuits remained stable; sometimes circuits drifted along the tissue and occasionally multiple wavelets were seen instead of a single circuit. CONCLUSIONS: Spatial nonhomogeneities in conduction caused by transient unexcitable areas play a major role in both the initiation and the termination of episodes of circus movements in the pregnant rat myo-metrium. In addition, most circuits remained in a single location, although sometimes meandering or even fibrillatory activity was seen.

Animals↗

The slow wave does not propagate across the gastroduodenal junction in the isolated feline preparation.

Detailed spatial analysis of the propagation of individual slow waves was performed in the isolated gastroduodenal preparation of the cat. Use was made of a system that allowed the simultaneous recordings from 240 extracellular electrodes, which were positioned across the gastroduodenal region. Reconstructions of the spread of propagation (n = 31) revealed that (a) the antral slow wave never propagated into the duodenum but was blocked at the pyloric ring, (b) the duodenal slow wave did not activate the antral tissue, and (c) a quiescent zone in which no slow waves could be recorded was always present at the most proximal part of the duodenum immediately distal to the pyloric ring. Furthermore, phase density distributions of duodenal cycles revealed that antral activity had no influence on the rate of discharge of duodenal pacemakers. Light microscopic study of sections of the duodenum close to the pyloric ring and further away did not show any structural differences between the quiescent zone and the active areas. In conclusion, slow waves do not propagate across the gastroduodenal junction in the isolated feline preparation and therefore do not seem to play a role in the electro-mechanical integration between the stomach and the duodenum.

Animals↗

Circulating excitations and re-entry in the pregnant uterus.

The propagation of individual action potentials during spontaneous bursts of activity in isolated pregnant rat myometrium in the final stage of pregnancy was analyzed. Simultaneous recordings from 240 extracellular recording sites (inter-electrode distance 1 mm) made it possible to reconstruct, in spatial and temporal details, the conduction of the electrical impulse. On several occasions, the impulse was seen to be conducted in a circular fashion whereby the impulse repeatedly re-excited the myometrium. No evidence was found of circuits rotating around an area of depressed excitability or anatomical obstacle, suggesting that these circuits are similar to those proposed to occur in cardiac muscle by the "leading circuit" model. Because of the anisotropic conduction properties of the myometrium, several circuits revolved in an ellipse with the long axis parallel to the longitudinal fiber direction, similar to functional re-entry in the anisotropic ventricle. Of a total of 46 bursts analyzed, myometrial re-entry occurred in 10 of the bursts. Furthermore, re-entries were found at day 17, day 19 and day 21 ( = term) stages of pregnancy suggesting that re-entry may occur throughout the final stage of gestation. In conclusion, functional re-entry, previously shown in the myocardium, may also occur in the pregnant myometrium. The presence of re-entry in the uterus could underlie the mechanism for uterine tachysystole, leading to dysfunctional labor.

Action Potentials↗

Disturbances in the propagation of the slow wave during acute local ischaemia in the feline small intestine.

OBJECTIVE AND DESIGN: The normal aborad propagation of the slow wave in the small intestine is easily distorted by pacing, hypoxia or transection. We studied whether acute local ischaemia would also induce serious conduction disturbances and ectopic pacemaking. METHODS: After general anaesthesia and a mid-abdominal incision, a multi-electrode array of 240 extracellular electrodes was positioned on the serosal surface of an exteriorized intestinal loop. Simultaneous recordings of all 240 surface electrodes was performed during a control period and for 5-10 min following local acute arterial occlusion. After the experiments activation maps were constructed describing the pattern of propagation of the slow waves. RESULTS: During control periods, the activation maps showed homogeneous aborad conduction of the slow wave. During acute ischaemia, local areas of inexcitability developed rapidly, merging together to form lines of conduction block. This in turn often provoked the appearance of subsidiary ectopic pacemakers. The location of the conduction blocks as well as that of ectopic pacemakers was highly variable and could disappear and reappear at other sites. CONCLUSION: Within minutes, acute ischaemia disturbed the organized homogeneous aborad propagation of the slow wave leading to pronounced inhomogeneous depression of conduction, local inexcitability, conduction block and the appearance of subsidiary pacemakers.

Acute Disease↗

High resolution electrical mapping in the gastrointestinal system: initial results.

High resolution electrical mapping in the gastrointestinal system entails recording from a large number of extracellular electrodes simultaneously. It allows the collection of signals from 240 individual sites which are then amplified, filtered, digitized, multiplexed and stored on tape. After recording, periods of interest can be analysed and the original sequence of activity reconstructed. This technology, originally developed to study normal rhythms and abnormal dysrhythmias in the heart, has been modified to allow recordings from the gastrointestinal tract. In this report, initial results are presented describing the origin and propagation of the slow wave in the isolated stomach and the isolated duodenum in the cat. These results show that in both organs it not uncommon to have more than one focus active during a single cycle. The conduction of slow waves from such a multiple pacemaker environment can become quite complex, and this may play a role in determining the contractile pattern in these organs.

Animals↗

Spatial and temporal variations in pacemaking and conduction in the isolated renal pelvis.

In renal pelvis preparations isolated from the sheep, the location of the pacemaker and the pathway of conduction of the electrical impulse in the pelvis were analyzed in detail. An electrophysiological acquisition system was used allowing simultaneous recordings from 240 extracellular electrodes. Reconstruction of the spread of activity showed that the site of the pelvis pacemaker was, in virtually all cases, located at the pelvicalyceal border and never in the body of the pelvis or in the area of the pelviureteric junction. One single pacemaker was responsible for a particular spread of activation, and fusion of activity originating from two or more pacemakers did not place. Furthermore, spontaneous shifts of the pacemaker could occur from one site to another along the pelvicalyceal border. Conduction from the site of the current pacemaker to the pelviureteric junction and the ureter was slow, inhomogeneous, and contorted. Multiple instances of partial or total conduction block were seen at all levels in the pelvis and were not restricted to the pelviureteric junction. The occurrence of the conduction block did not seem to be related to the length of the preceding interval, implying that the refractory period did not play a major role in the genesis of intrapelvic conduction block. In conclusion, high-resolution mapping of the renal pelvis is possible and reveals location and behavior of the pacemaker and documents inhomogeneities in conduction and conduction block.

Animals↗

Wave mapping: detection of co-existing multiple wavefronts in high-resolution electrical mapping.

High-resolution mapping makes it possible to reconstruct and display the conduction pattern of the action potential as it propagates through cardiac or smooth muscles. During slow and regular activity, time mapping of the spread of activation muscles. During slow and regular activity, time mapping of the spread of activation is relatively simple and straightforward. However, when frequencies are high or conduction is slow, such as seen during atrial fibrillation or found in the pregnant uterus, the tracking of individual waves may become more difficult and uncertain. In order to reconstruct the pathway of a single wave, a search and sorting routine was developed which makes it possible to distinguish, track and display individual wavelets. The algorithm is able to detect variations in conduction block, spontaneous shifts in the location of the pacemaker and changes in the direction of conduction. It is less sensitive when two or more wavefronts intermingle in space and time, such as during collision or fusion. Wave mapping is especially useful, in addition to current time mapping, in sorting quickly through the large amount of data produced by high-resolution mapping of electrical activities in cardiac and smooth muscle.

Action Potentials↗

Spatial and temporal variations in local spike propagation in the myometrium of the 17-day pregnant rat.

Detailed spatial analysis of propagation of individual action potential was performed during spontaneous bursts of activity in the isolated 17-day pregnant rat myometrium. Use was made of high-resolution mapping with simultaneous recordings from 240 extracellular electrodes. Positioning of the electrode assembly by itself did not have any adverse effects, and no differences were found in the period or duration of spontaneous bursts recorded with and without the electrode assembly touching the tissue. The spread of propagation of individual action potentials was reconstructed at several moments during myometrial spike bursts. Both the direction and the sequence of activation of the myometrium were found to be highly variable and depended on 1) the level and spatial dispersion of excitability and 2) whether conduction occurred predominantly in the longitudinal or the circumferential direction. Furthermore, conduction was frequently complicated by the spontaneous occurrence of 1) lines of conduction block, 2) focal sites of pacemaking, or 3) merging of two or more wavelets into a single wave. In contrast, when the myometrium was divided into small segments, activity became much more regular, and both the location of the pacemaker and the direction of propagation were much more stable than in the whole myometrium. In conclusion, spontaneous spatial variations in local spike propagation at the preterm stage could provide for the necessary asynchrony in activation and play a role in the prevention of forceful contractions and premature labor.

Action Potentials↗

Multielectrode mapping of slow-wave activity in the isolated rabbit duodenum.

The technique of multiple simultaneous recordings from a large number of extracellular electrodes (> 100) is currently used in the study of normal and abnormal electrical conduction in the heart and the genesis of cardiac arrhythmias. To investigate whether such a system could also be applied in gastrointestinal electrophysiology, several studies were performed with this technique on segments of isolated rabbit duodenum. A multiple-electrode assembly consisting of 240 silver wires was positioned on the serosal surface of the duodenum, and the recorded signals were, after suitable processing, stored. Thereafter, analysis of all simultaneously recorded slow waves during a selected period of time was performed to reconstruct the pattern of conduction in the duodenum. The first results show that there is a considerable variation in conduction pattern, which is determined by the site of the natural pacemaker. Several experiments were performed to rule out possible deleterious effects of positioning the multiple-electrode assembly on the duodenum. Furthermore, prolonged periods of recording did not influence propagation speed and pattern provided that the positioning of the multiple electrode assembly was performed with care. Entrainment of the natural pacemaker was possible by applying electrical stimuli through 2 of the 240 extracellular electrodes during simultaneous recordings. In conclusion, multisite extracellular mapping of gastrointestinal smooth muscle is possible and can be used to study origin and spread of slow-wave activity.

Animals↗

Pathophysiology of atrial fibrillation: current aspects.

The existence of independent wandering wavelets as the basis for fibrillation was postulated by Moe and coworkers in their multiple wavelet theory and was later confirmed in both animal and human atria. The process of initiation of fibrillation however is less clear but probably depends on a) an increase in inhomogeneity in conduction and b) a decrease in the length of the excitation wave. Recently a method has been introduced to quantify inhomogeneity in conduction in isolated rabbit atria. Already during slow basic rhythm, inhomogeneties based on structural inhomogeneities could be identified. Premature activation increased conduction inhomogeneities in the neighborhood of the premature stimuli while rapid pacing induced the highest degree of inhomogeneity throughout the myocardium. The role of the second prerequisite for atrial fibrillation, the length of the excitation wave, has also recently been studied in chronic instrumented conscious dogs. Conduction velocities, refractory periods and wavelengths were measured during the administration of a variety of drugs and correlated with the induction of atrial arrhythmias. The predictive power of the wavelength was much higher than for refractory period or conduction velocity alone. Upon gradual reduction of the wavelength, first rapid repetitive responses, then atrial flutter, and finally atrial fibrillation was observed. In summary, at least two factors are of importance for the initiation of atrial fibrillation: inhomogeneity in conduction and a short excitation wave. Other factors, such as abnormalities in atrial structure and function will certainly modify the contribution of these factors to an extent that remains to be investigated.

Animals↗

Vulnerability of rabbit atrium to reentry by hypoxia. Role of inhomogeneity in conduction and wavelength.

In isolated superfused left atria of the rabbit, the inducibility of tachyarrhythmias by single early premature stimuli was highly increased by hypoxia. High-resolution mapping showed that these arrhythmias were caused by circus movement around a functional arc of conduction block (leading circle reentry). To determine the electrophysiological changes by hypoxia responsible for the higher vulnerability to intra-atrial reentry, the wavelength of the atrial impulse and spatial inhomogeneities in refractory periods and local conduction delays were measured. Hypoxia caused a transient increase in refractory periods during the first 10-15 min of hypoxia. After this period, refractory periods shortened again to values slightly lower than during control. During the whole period of hypoxia, local differences in refractory periods were enlarged. Conduction velocity was significantly depressed by hypoxia. As a result, the wavelength of the atrial impulse gradually shortened during hypoxia to approximately 80% of control. Inhomogeneity in conduction was quantified by phase maps in which the maximal local delays in conduction are plotted. Hypoxia caused a marked increase in inhomogeneity in conduction both during slow rhythm (inhomogeneity index increased from 2.3 to 3.4) and premature activation (from 3.1 to 4.7). We conclude that the higher vulnerability of the atrium for reentrant arrhythmias by hypoxia is based on a combination of a moderate shortening of the wavelength and an increase in inhomogeneity in conduction of premature wavefronts.

Action Potentials↗

Anisotropic conduction and reentry in perfused epicardium of rabbit left ventricle.

An experimental model of anisotropy was developed, consisting of a thin layer (1 mm) of perfused ventricular epicardium created by cryodestruction of the interventricular septum and the inner four-fifths of the free wall of the left ventricle. The electrophysiological properties of the 1-mm-thick surviving layer were the same as before freezing. Epicardial conduction was mapped with a 192-fold mapping electrode (spatial resolution 1 mm). In the intact ventricle transverse conduction was interrupted near the site of stimulation by epicardial breakthrough of faster intramural wavefronts, whereas in the thin epicardial layer transverse conduction proceeded over a much longer distance, resulting in enlargement of the area of effective anisotropy. Induction of premature beats or incremental pacing resulted in the development of lines of transverse conduction block. The occurrence of transverse conduction block, however, only rarely led to reentry, because fast longitudinal activation of the tissue distal to the line of block provided insufficient delay for the fibers proximal to the line of block to restore their excitability. Initiation of reentry was associated with the development of longitudinal arcs of conduction block during which the area distal to the line of block was activated by a slowly propagating transverse wavefront providing a longer delay for the proximal fibers to restore their excitability. In conclusion, thin layers of myocardium may provide a substrate for reentry because of enlargement of the effective area of anisotropy.

Animals↗

Memory-conjunction errors: miscombination of stored stimulus features can produce illusions of memory.

We demonstrate that subjects will often claim to have previously seen a new stimulus if they have previously seen stimuli containing its component features. Memory for studied stimuli was measured using a "yes"/"no" recognition test. There were three types of test stimuli: target stimuli, which had been presented during study, conjunction stimuli, constructed by combining the features of separate study stimuli, and feature stimuli, in which studied stimulus features were combined with new, unstudied, features. For both nonsense words and faces, the subjects made many more false alarms for conjunction than for feature stimuli. Additional experiments demonstrated that the results were not due to physical similarity between study and test stimuli and that conjunction errors were much more common than feature errors in recall. The results demonstrate that features of stored stimuli maintain some independence in memory and can be incorrectly combined to produce recognition errors.

Humans↗