Lukasz Wiklendt

Design of a high-sensor count fibre optic manometry catheter for in-vivo colonic diagnostics

The design of a fibre Bragg grating based manometry catheter for in-vivo diagnostics in the human colon is presented. The design is based on a device initially developed for use in the oesophagus, but in this instance, longer sensing lengths and increased flexibility were required to facilitate colonoscopic placement of the device and to allow access to the convoluted regions of this complex organ. The catheter design adopted allows the number of sensing regions to be increased to cover extended lengths of the colon whilst maintaining high flexibility and the close axial spacing necessary to accurately record pertinent features of peristalsis. Catheters with 72 sensing regions with an axial spacing of 1 cm have been assembled and used in-vivo to record peristaltic contractions in the human colon over a 24hr period. The close axial spacing of the pressure sensors has, for the first time, identified the complex nature of propagating sequences in both antegrade (towards the anus) and retrograde (away from the anus) directions in the colon. The potential to miss propagating sequences at wider sensor spacings is discussed and the resultant need for close axial spacing of sensors is proposed.

Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow‐transit constipation

Sacral nerve stimulation (SNS) is emerging as a potential treatment for patients with constipation. Although SNS can elicit an increase in colonic propagating sequences (PSs), the optimal stimulus parameters for this response remain unknown. This study evaluated the colonic motor response to subsensory and suprasensory SNS in patients with slow‐transit constipation.

The effect of sacral nerve stimulation on distal colonic motility in patients with faecal incontinence

Sacral nerve stimulation (SNS) is an effective treatment for neurogenic faecal incontinence (FI). However, the clinical improvement that patients experience cannot be explained adequately by changes in anorectal function. The aim of this study was to examine the effect of SNS on colonic propagating sequences (PSs) in patients with FI in whom urgency and incontinence was the predominant symptom.

Quantification of in vivo colonic motor patterns in healthy humans before and after a meal revealed by high-resolution fiber-optic manometry.

Until recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques.

Colonic motor abnormalities in slow transit constipation defined by high resolution, fibre-optic manometry

Slow transit constipation (STC) is associated with colonic motor abnormalities. The underlying cause(s) of the abnormalities remain poorly defined. In health, utilizing high resolution fiber‐optic manometry, we have described a distal colonic propagating motor pattern with a slow wave frequency of 2–6 cycles per minute (cpm). A high calorie meal caused a rapid and significant increase in this activity, suggesting the intrinsic slow wave activity could be mediated by extrinsic neural input. Utilizing the same protocol our aim was to characterize colonic meal response STC patients.

An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans.

Low‐resolution colonic manometry leads to a gross misinterpretation of the frequency and polarity of propagating sequences: Initial results from fiber‐optic high‐resolution manometry studies

High‐resolution manometry catheters are now being used to record colonic motility. The aim of this study was to determine the influence of pressure sensor spacing on our ability to identify colonic propagating sequences (PS).

Neural mechanisms of peristalsis in the isolated rabbit distal colon: a neuromechanical loop hypothesis

Propulsive contractions of circular muscle are largely responsible for the movements of content along the digestive tract. Mechanical and electrophysiological recordings of isolated colonic circular muscle have demonstrated that localized distension activates ascending and descending interneuronal pathways, evoking contraction orally and relaxation anally. These polarized enteric reflex pathways can theoretically be sequentially activated by the mechanical stimulation of the advancing contents. Here, we test the hypothesis that initiation and propagation of peristaltic contractions involves a neuromechanical loop; that is an initial gut distension activates local and oral reflex contraction and anal reflex relaxation, the subsequent movement of content then acts as new mechanical stimulus triggering sequentially reflex contractions/relaxations at each point of the gut resulting in a propulsive peristaltic contraction. In fluid filled isolated rabbit distal colon, we combined spatiotemporal mapping of gut diameter and intraluminal pressure with a new analytical method, allowing us to identify when and where active (neurally-driven) contraction or relaxation occurs. Our data indicate that gut dilation is associated with propagating peristaltic contractions, and that the associated level of dilation is greater than that preceding non-propagating contractions (2.7 ± 1.4 mm vs. 1.6 ± 1.2 mm; P < 0.0001). These propagating contractions lead to the formation of boluses that are propelled by oral active neurally driven contractions. The propelled boluses also activate neurally driven anal relaxations, in a diameter dependent manner. These data support the hypothesis that neural peristalsis is the consequence of the activation of a functional loop involving mechanical dilation which activates polarized enteric circuits. These produce propulsion of the bolus which activates further anally, polarized enteric circuits by distension, thus closing the neuromechanical loop.

Neuromechanical factors involved in the formation and propulsion of fecal pellets in the guinea-pig colon

The neuromechanical processes involved in the formation and propulsion of fecal pellets remain incompletely understood.

Upper esophageal sphincter mechanical states analysis: a novel methodology to describe UES relaxation and opening

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation of neural inputs to these muscles, the intrinsic cricopharyngeus muscle and extrinsic suprahyoid muscles, results in their contraction or relaxation, which changes the diameter of the lumen, alters the intraluminal pressure and ultimately inhibits or promotes flow of content. This relationship that exists between the changes in diameter and concurrent changes in intraluminal pressure has been used previously to calculate the “mechanical states” of the muscle; that is when the muscles are passively or actively, relaxing or contracting. Diseases that alter the neural pathways to these muscles can result in weakening the muscle contractility and/or decreasing the muscle compliance, all of which can cause dysphagia. Detecting these changes in the mechanical state of the muscle is difficult and as the current interpretation of UES motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during swallow can be missed. We hypothesized that quantification of mechanical states of the UES and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern the timing and extent of UES opening during swallowing. To achieve this we initially analyzed swallows captured by simultaneous videofluoroscopy and UES pressure with impedance recording. From these data we demonstrated that intraluminal impedance measurements could be used to determine changes in the internal diameter of the lumen when compared to videofluoroscopy. Then using a database of pressure-impedance studies, recorded from young and aged healthy controls and patients with motor neuron disease, we calculated the UES mechanical states in relation to a standardized swallowed bolus volume, normal aging and dysphagia pathology. Our results indicated that eight different mechanical states were almost always seen during healthy swallowing and some of these calculated changes in muscle function were consistent with the known neurally dependent phasic discharge patterns of cricopharyngeus muscle activity during swallowing. Clearly defined changes in the mechanical states were observed in motor neuron disease when compared to age matched healthy controls. Our data indicate that mechanical state predictions were simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.