-
American Journal of Physiology.... Dec 2013We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis...
We recently identified hexamethonium-resistant peristalsis in the guinea pig colon. We showed that, following acute blockade of nicotinic receptors, peristalsis recovers, leading to normal propagation velocities of fecal pellets along the colon. This raises the fundamental question: what mechanisms underlie hexamethonium-resistant peristalsis? We investigated whether blockade of the major receptors that underlie excitatory neuromuscular transmission is required for hexamethonium-resistant peristalsis. Video imaging of colonic wall movements was used to make spatiotemporal maps and determine the velocity of peristalsis. Propagation of artificial fecal pellets in the guinea pig distal colon was studied in hexamethonium, atropine, ω-conotoxin (GVIA), ibodutant (MEN-15596), and TTX. Hexamethonium and ibodutant alone did not retard peristalsis. In contrast, ω-conotoxin abolished peristalsis in some preparations and reduced the velocity of propagation in all remaining specimens. Peristalsis could still occur in some animals in the presence of hexamethonium + atropine + ibodutant + ω-conotoxin. Peristalsis never occurred in the presence of TTX. The major finding of the current study is the unexpected observation that peristalsis can occur after blockade of the major excitatory neuroneuronal and neuromuscular transmitters. Also, the colon retained an intrinsic polarity in the presence of these antagonists and was only able to expel pellets in an aboral direction. The nature of the mechanism(s)/neurotransmitter(s) that generate(s) peristalsis and facilitate(s) natural fecal pellet propulsion, after blockade of major excitatory neurotransmitters, at the neuroneuronal and neuromuscular junction remains to be identified.
Topics: Animals; Colon; Drug Resistance; Gastrointestinal Transit; Guinea Pigs; Hexamethonium; Neuromuscular Blocking Agents; Neuromuscular Junction; Peristalsis; Receptors, Muscarinic; Receptors, Neurokinin-2; Receptors, Nicotinic; Recovery of Function; Spatio-Temporal Analysis; Synaptic Transmission
PubMed: 24113766
DOI: 10.1152/ajpgi.00257.2013 -
Acta Gastro-enterologica Belgica 2022Sedation impairs full visualization of the esophagogastric junction (EGJ) and Z line (the squamocolumnar junction) during esophagogastroduodenoscopy (EGD). The aim of...
BACKGROUND AND STUDY AIMS
Sedation impairs full visualization of the esophagogastric junction (EGJ) and Z line (the squamocolumnar junction) during esophagogastroduodenoscopy (EGD). The aim of this study was to determine whether induction of esophageal peristalsis could improve the ability to evaluate the Z line in children and adolescents.
PATIENTS AND METHODS
Study 1: Consecutive patients (10-15 years) undergoing EGD with propofol or midazolam sedation were enrolled. The proportion of Z line observed was compared between the two groups. Study 2: The effect of an air infusion near the EGJ following deflation of the stomach to induce esophageal peristalsis was investigated in the patients (15-18 years), undergoing EGD with propofol sedation. The proportion of Z line observed was compared between the stimulated group and control group.
RESULTS
Study 1: 149 patients were evaluated; 87 received propofol (43 boys; average age 13.2 years (range, 10-15)) and 62 received midazolam (30 boys; average age 12.8 years (range, 10-15)). The proportion of the Z line visualized was low but was greater with propofol vs. midazolam sedation (36.8% vs 16.1%, P=0.0059). Study 2: 102 patients were evaluated; 62 had induction of peristalsis (34 boys; average age 16.2 years (range, 15-18)) and 40 controls (20 boys; average age 16.8 years (range, 15-18)). Complete visualization of the Z line achieved in 95% (59 of 62) following induction of peristalsis vs. 37.5% (15 of 40) of controls (P>0.001).
CONCLUSIONS
Induction of esophageal peristalsis greatly improved visualization of the Z line during sedated EGD in children and adolescents.
Topics: Adolescent; Child; Endoscopy, Digestive System; Esophagogastric Junction; Humans; Hypnotics and Sedatives; Male; Midazolam; Peristalsis
PubMed: 35304989
DOI: 10.51821/85.1.9240 -
Proceedings of the National Academy of... May 2022The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by...
The peristaltic reflex is a fundamental behavior of the gastrointestinal (GI) tract in which mucosal stimulation activates propulsive contractions. The reflex occurs by stimulation of intrinsic primary afferent neurons with cell bodies in the myenteric plexus and projections to the lamina propria, distribution of information by interneurons, and activation of muscle motor neurons. The current concept is that excitatory cholinergic motor neurons are activated proximal to and inhibitory neurons are activated distal to the stimulus site. We found that atropine reduced, but did not block, colonic migrating motor complexes (CMMCs) in mouse, monkey, and human colons, suggesting a mechanism other than one activated by cholinergic neurons is involved in the generation/propagation of CMMCs. CMMCs were activated after a period of nerve stimulation in colons of each species, suggesting that the propulsive contractions of CMMCs may be due to the poststimulus excitation that follows inhibitory neural responses. Blocking nitrergic neurotransmission inhibited poststimulus excitation in muscle strips and blocked CMMCs in intact colons. Our data demonstrate that poststimulus excitation is due to increased Ca2+ transients in colonic interstitial cells of Cajal (ICC) following cessation of nitrergic, cyclic guanosine monophosphate (cGMP)-dependent inhibitory responses. The increase in Ca2+ transients after nitrergic responses activates a Ca2+-activated Cl− conductance, encoded by Ano1, in ICC. Antagonists of ANO1 channels inhibit poststimulus depolarizations in colonic muscles and CMMCs in intact colons. The poststimulus excitatory responses in ICC are linked to cGMP-inhibited cyclic adenosine monophosphate (cAMP) phosphodiesterase 3a and cAMP-dependent effects. These data suggest alternative mechanisms for generation and propagation of CMMCs in the colon.
Topics: Colon; Gastrointestinal Motility; Interstitial Cells of Cajal; Myocytes, Smooth Muscle; Peristalsis
PubMed: 35446689
DOI: 10.1073/pnas.2123020119 -
American Journal of Physiology.... Apr 2019Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction, which can easily be measured in humans using high-resolution...
Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction, which can easily be measured in humans using high-resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. The aim of this study was to determine the effect of posture on the temporal and quantitative relationship between distension and contraction along the entire length of the esophagus in normal healthy subjects by using concurrent HRM, HRM impedance (HRMZ), and intraluminal ultrasound (US). Studies were conducted in 15 normal healthy subjects in the supine and Trendelenburg positions. Both manual and automated methods were used to extract quantitative pressure and impedance-derived features from the HRMZ recordings. Topographical plots of distension and contraction were visualized along the entire length of the esophagus. Distension was also measured from the US images during 10-ml swallows at 5 cm above the lower esophageal sphincter. Each swallow was associated with luminal distension followed by contraction, both of which traversed the esophagus in a sequential/peristaltic fashion. Luminal distension (US) and esophageal contraction amplitude were greater in the Trendelenburg compared with the supine position. Length of esophageal breaks (in the transition zone) were reduced in the Trendelenburg position. Change in posture altered the temporal relationship between distension and contraction, and bolus traveled closer to the esophageal contraction in the Trendelenburg position. Topographical contraction-distension plots derived from HRMZ recordings is a novel way to visualize esophageal peristalsis. Future studies should investigate if abnormalities of esophageal distension are the cause of functional dysphagia. NEW & NOTEWORTHY Ascending contraction and descending inhibition are two important components of peristalsis. High-resolution manometry only measures the contraction phase of peristalsis. We measured esophageal distension from intraluminal impedance recordings and developed novel contraction-distension topographical plots to prove that similar to contraction, distension also travels in a peristaltic fashion. Change in posture from the supine to the Trendelenburg position also increased the amplitude of esophageal distension and contraction and altered the temporal relationship between distension and contraction.
Topics: Adult; Deglutition; Digestive System Physiological Phenomena; Electric Impedance; Esophagus; Female; Humans; Male; Manometry; Muscle Contraction; Patient Positioning; Peristalsis; Posture
PubMed: 30676774
DOI: 10.1152/ajpgi.00397.2018 -
Communications Biology Dec 2023Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and...
Assessing gastrointestinal motility lacks simultaneous evaluation of intraluminal pressure (ILP), circular muscle (CM) and longitudinal muscle (LM) contraction, and lumen emptying. In this study, a sophisticated machine was developed that synchronized real-time recordings to quantify the intricate interplay between CM and LM contractions, and their timings for volume changes using high-resolution cameras with machine learning capability, the ILP using pressure transducers and droplet discharge (DD) using droplet counters. Results revealed four distinct phases, B, N, D, and A, distinguished by pressure wave amplitudes. Fluid filling impacted LM strength and contraction frequency initially, followed by CM contraction affecting ILP, volume, and the extent of anterograde, retrograde, and segmental contractions during these phases that result in short or long duration DD. This comprehensive analysis sheds light on peristalsis mechanisms, understand their sequence and how one parameter influenced the other, offering insights for managing peristalsis by regulating smooth muscle contractions.
Topics: Animals; Mice; Peristalsis; Gastrointestinal Motility; Muscle Contraction; Intestine, Small
PubMed: 38062160
DOI: 10.1038/s42003-023-05631-2 -
British Journal of Pharmacology Jan 2013Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age,... (Review)
Review
Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance.
Topics: Aged; Animals; Disease Models, Animal; Electric Stimulation; Female; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; In Vitro Techniques; Individuality; Intestine, Small; Male; Models, Biological; Motilin; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Neurons; Neuropharmacology; Peristalsis; Receptors, Serotonin; Research Design; Species Specificity; Synaptic Transmission; Translational Research, Biomedical
PubMed: 22946540
DOI: 10.1111/j.1476-5381.2012.02198.x -
The Journal of Thoracic and... Dec 2020Esophageal aperistalsis has been considered a relative contraindication for lung transplant because of a higher risk of allograft dysfunction secondary to reflux and...
OBJECTIVE
Esophageal aperistalsis has been considered a relative contraindication for lung transplant because of a higher risk of allograft dysfunction secondary to reflux and aspiration induced by poor esophageal clearance. We previously reported that esophageal motility improves in some patients after lung transplant. We reviewed the clinical course of lung transplant recipients diagnosed with an aperistaltic esophagus on pretransplant testing.
METHODS
We identified patients diagnosed with pretransplant aperistaltic esophagus on high-resolution manometry who underwent lung transplant. Recipients with normal esophageal motility before lung transplant were used as the propensity score-matched control group. High-resolution manometry was repeated after lung transplant, and patients with aperistalsis were further divided into 2 subgroups: improved esophageal peristalsis and nonimproved peristalsis (ie, persistent aperistalsis after lung transplant).
RESULTS
Esophageal aperistalsis was seen in 31 patients (mean age, 59.0 years; 21 men). The 1-, 3-, and 5-year post-lung transplant survivals in the aperistalsis group were 80.6%, 51.2%, and 34.9%, respectively, which was significantly lower than in the control group (90.3%, 73.4%, and 58.8%, respectively; P = .038). Post-lung transplant high-resolution manometry was performed for 29 patients in the aperistalsis group, 19 of whom demonstrated improved esophageal motility (65.5%). The 1-, 3-, and 5-year survivals after lung transplant of patients with recovery of peristalsis were similar to those of the control group (89.5%, 65.0%, and 48.8%, respectively; P = 1.000), whereas the nonimproved peristalsis group had lower survival (80.0%, 36.0%, and data unavailable, respectively; P = .012).
CONCLUSIONS
Esophageal aperistalsis is not necessarily a contraindication for lung transplant. Improved peristalsis can be expected in up to two-thirds of these patients and is associated with good outcomes.
Topics: Aged; Deglutition Disorders; Esophageal pH Monitoring; Esophagus; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Lung Transplantation; Male; Manometry; Middle Aged; Peristalsis; Prognosis; Prospective Studies; Recovery of Function; Respiratory Insufficiency; Time Factors
PubMed: 32197903
DOI: 10.1016/j.jtcvs.2019.12.120 -
The Journal of Thoracic and... Dec 2020
Topics: Humans; Lung Transplantation; Peristalsis; Transplants
PubMed: 32197909
DOI: 10.1016/j.jtcvs.2020.02.070 -
Neurogastroenterology and Motility Oct 2021Functional luminal imaging probe (FLIP) Panometry assesses the esophageal response to distention and may complement the assessment of primary peristalsis on...
Evaluating esophageal motility beyond primary peristalsis: Assessing esophagogastric junction opening mechanics and secondary peristalsis in patients with normal manometry.
BACKGROUND
Functional luminal imaging probe (FLIP) Panometry assesses the esophageal response to distention and may complement the assessment of primary peristalsis on high-resolution manometry (HRM). We aimed to investigate whether FLIP Panometry provides complementary information in patients with normal esophageal motility on HRM.
METHODS
Adult patients that completed FLIP and had an HRM classification of normal motility were retrospectively identified for inclusion. 16-cm FLIP studies performed during endoscopy were evaluated to assess EGJ distensibility, secondary peristalsis, and identify an abnormal response to distention involving sustained LES contraction (sLESC). Clinical characteristics and esophagram were assessed when available.
KEY RESULTS
Of 164 patients included (mean(SD) age 48(16) years, 75% female), 111 (68%) had normal Panometry with EGJ-distensibility index (DI) ≥2.0 mm /mmHg, maximum EGJ diameter ≥16mm and antegrade contractions. Abnormal EGJ distensibility was observed in 44/164 (27%), and 38/164 (23%) had an abnormal contractile response to distension. sLESC was observed in 11/164 (7%). Among 68 patients that completed esophagram, abnormal EGJ distensibility was more frequently observed with an abnormal esophagram than normal EGJ opening: 14/23 (61%) vs 10/45 (22%); P=0.003. Epiphrenic diverticula were present in 3/164 patients: 2/3 had sLESC.
CONCLUSIONS & INFERENCES
Symptomatic patients with normal esophageal motility on HRM predominantly have normal FLIP Panometry; however, abnormal FLIP findings can be observed. While abnormal Panometry findings appear clinically relevant via an association with abnormal bolus retention, complementary tests, such as provocative maneuvers with HRM and timed barium esophagram, are useful to determine clinical context.
Topics: Adult; Endoscopy, Gastrointestinal; Esophageal Achalasia; Esophagogastric Junction; Female; Humans; Male; Manometry; Middle Aged; Peristalsis; Retrospective Studies
PubMed: 33705590
DOI: 10.1111/nmo.14116 -
World Journal of Gastroenterology Oct 2015Capsule endoscopes have evolved from passively moving diagnostic devices to actively moving systems with potential therapeutic capability. In this review, we will... (Review)
Review
Capsule endoscopes have evolved from passively moving diagnostic devices to actively moving systems with potential therapeutic capability. In this review, we will discuss the state of the art, define the current shortcomings of capsule endoscopy, and address research areas that aim to overcome said shortcomings. Developments in capsule mobility schemes are emphasized in this text, with magnetic actuation being the most promising endeavor. Research groups are working to integrate sensor data and fuse it with robotic control to outperform today's standard invasive procedures, but in a less intrusive manner. With recent advances in areas such as mobility, drug delivery, and therapeutics, we foresee a translation of interventional capsule technology from the bench-top to the clinical setting within the next 10 years.
Topics: Animals; Capsule Endoscopes; Capsule Endoscopy; Drug Delivery Systems; Equipment Design; Humans; Magnetics; Peristalsis; Robotics; Video Recording
PubMed: 26457013
DOI: 10.3748/wjg.v21.i37.10528