Changes In Intraluminal Pressure Research Articles

Arterial Myogenic Response and Aging.

The arterial myogenic response is an inherent property of resistance arteries. Myogenic tone is crucial for maintaining a relatively constant blood flow in response to changes in intraluminal pressure and protects delicate organs from excessive blood flow. Although this fundamental physiological phenomenon has been extensively studied, the underlying molecular mechanisms are largely unknown. Recent studies identified a crucial role of mechano-activated angiotensin II type 1 receptors (AT1R) in this process. The development of myogenic response is affected by aging. In this review, we summarize recent progress made to understand the role of AT1R and other mechanosensors in the control of arterial myogenic response. We discuss age-related alterations in myogenic response and possible underlying mechanisms and implications for healthy aging.

Intravascular optical coherence elastography.

Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), visualizes tissue strain to deduce the tissue's biomechanical properties. In this study, we demonstrate intravascular OCE using a 1.1 mm motorized catheter and a 1.6 MHz Fourier domain mode-locked OCT system. We induced an intraluminal pressure change by varying the infusion rate from the proximal end of the catheter. We analysed the pixel-matched phase change between two different frames to yield the radial strain. Imaging experiments were carried out in a phantom and in human coronary arteries in vitro. At an imaging speed of 3019 frames/s, we were able to capture the dynamic strain. Stiff inclusions in the phantom and calcification in atherosclerotic plaques are associated with low strain values and can be distinguished from the surrounding soft material, which exhibits elevated strain. For the first time, circumferential intravascular OCE images are provided side by side with conventional OCT images, simultaneously mapping both the tissue structure and stiffness.

Intraluminal Pressure, Multi‐Dimensional Field Imaging and Fluid Volume Recordings as a Useful Tool to Determine Peristaltic Propulsion

IntroductionPeristalsis is a collective process of intestinal muscle contractions for the passage of food through the gastrointestinal tract. Although, peristalsis has been extensively studied using spatiotemporal mapping and pressure transducers both in vivo and in vitro, the quantitative analysis of peristaltic propulsion is not fully understood. Lack of a definitive tool therefore, limited drug discovery in the field of constipation including IBSC. In this study, we used directional lighting, advanced field‐imaging techniques together with intraluminal pressure recordings to determine intestinal diameter, frequency of longitudinal muscle activity and pressure changes as well as velocity of anterograde and retrograde contractions and volume output measurements to help determine the net peristaltic activity.MethodsThe basal activity of intestinal peristalsis in terms of intraluminal pressure (ILP) changes, real‐time changes in longitudinal muscle activity and intestinal lumen diameter were measured in approximately 5 cm long segments from jejunum of mouse small intestine (male, NIH Swiss) in physiological Ringer solution. Intraluminal pressure was recorded using pressure transducers connected to the oral and aboral end of each segment mounted in Perfusion Bath for Tubular Organs, (Harvard apparatus, USA). Longitudinal muscle activity was studied using CVX400 series vision system, and LumiTrax™multi‐spectrum light (Keyence, USA) using multiple tracking points in each intestinal segment. The number, strength, and amplitude of oscillations in terms of intraluminal pressure changes and longitudinal muscle activity was analyzed using custom written programs. Luminal volume output was measured using a photo‐electric drop counter unit.ResultsThe number, amplitude, duration, and frequency of high and low amplitude changes in ILP and longitudinal muscle activity was determined using a lab‐written program. The frequency of longitudinal muscle activity correlated well with the frequency of low and high amplitude pressure changes. Frequency of both these oscillations were found to be 0.7 Hz. A reduction in the ILP was found to induce high amplitude contractions which subsided as the ILP increased. Changes in intestinal diameter with time correlated to ILP changes. A reduction in luminal diameter caused an increase in ILP and when not fully compensated caused increased fluid output. The mean velocity of the contractions over time in the regions tracked was determined to be 2.5 – 2.7mm/sec with peak anterograde contraction velocity of ‐4.06 mm/sec and retrograde contractions of 12 mm/sec. This mean velocity in presence of physiological Ringer solution was thought to determine the direction of contractions along the length of the GI tract under normal conditions.InferenceFrequency of longitudinal muscle activity and ILP oscillation showed similar frequency suggesting common pacemaker activity. The velocity of the contraction and volume output over time will help determine the overall peristaltic movement and could be used as a helpful index to gauge constipation.

Abstract 14369: Smooth Muscle Specific Deletion of RSK2 Suppresses Vasoconstriction of Resistance Arteries

Introduction: Intracellular Ca 2+ is a vital second messenger that plays a fundamental role in regulating intraluminal pressure- and agonist-induced vasoconstriction. Our laboratory previously demonstrated that intraluminal pressure and G-protein coupled receptor agonist stimulation activate p90 ribosomal S6 kinase 2 (RSK2). RSK2, in turn, phosphorylates the regulatory light chain of myosin (RLC 20 ) to induce constriction of small, resistance-sized arteries. More recently, we discovered that resistance arteries from global KO RSK2 mice exhibited a more dilated luminal diameter, reduced myogenic tone and RLC 20 phosphorylation, and decreased blood pressure. However, it is unclear whether the observed effects are a result of RSK2 global deletion in the mouse which may cause developmental abnormalities affecting the cardiovascular system. Hypothesis: We hypothesize that smooth muscle-specific RSK2 signaling in mouse resistance arteries is a significant regulator of myogenic tone and arterial stiffness. Methods: Inducible smooth muscle-specific KO mice for RSK2 (RSK2 SMC-/- ) were generated to study the role of RSK2 signaling in the regulation of vascular tone. Pressure myography studies assessed vascular reactivity in 4 th - and 5 th -order mesenteric arteries (MAs) isolated from RSK2 SMC-/- and RSK2 fl/fl mice. Results: The downregulation of normal RSK2 expression in resistance arteries was confirmed by Western blot. Our data shows that the intraluminal pressure-induced constriction of MAs is significantly attenuated in RSK2 SMC-/- mice (n=7 each group). Additionally, RSK2 SMC-/- resistance arteries experienced a delay in development of myogenic tone at 40 mmHg indicating that RSK2 signaling is sensitive to small changes in intraluminal pressure. Furthermore, MAs from RSK2 SMC-/- mice exhibited decreased vascular stiffness (indicated by enhanced strain, and rightward shift of stress-strain relationship) when compared to MAs from RSK2 fl/fl mice. Conclusions: This study provides novel evidence that smooth muscle RSK2 signaling contributes to pressure-induced vasoconstriction, and vascular stiffness. Inhibiting smooth muscle RSK2 activity may represent a novel strategy for rescuing vascular function in hypertensive patients.

Abstract P247: Elastin Insufficiency Impairs Renal Hemodynamics And Accelerates Aging-associated Structural And Functional Remodeling Of Preglomerular Arterioles

Elastin degradation and fragmentation are hallmarks of arterial stiffness and renal dysfunction associated with aging. However, it is unclear whether elastin insufficiency contributes to the changes in the structure and function of the resistance vasculature of the kidney during aging. Here we determined how increased vascular stiffness due to elastin insufficiency alters renal hemodynamics and mechanical properties of preglomerular arterioles. We assessed renal hemodynamics under anesthesia in 14-16-month-old female wild type (WT) and elastin heterozygous ( Eln +/- ) mice. Renal autoregulation was assessed by a stepwise increase in renal perfusion pressure (RPP) by simultaneously occluding the superior mesenteric and celiac arteries. Myogenic constriction and arterial stiffness were assessed by pressure myography of isolated renal interlobar arteries. Baseline renal vascular resistance (RVR) was elevated in Eln +/- mice (13.8 ± 2.9 vs 11.2 ± 1.4 mmHg/μL/min/g left kidney weight), while systolic blood pressure (SBP; 75.1 ± 7.4 vs 91 ± 4.2mmHg), renal blood flow (RBF; 6.3 ± 1.2 vs 7.4 ± 1.7 μL/min/g left kidney weight), renal plasma flow (RPF; 3.4 ± 0.8 vs 5 ± 1.2 mL/min/g/ left kidney weight) and urine flow rate, all trended lower in Eln +/- mice compared to WT mice. Glomerular filtration rate (GFR) and filtration fraction (FF) were similar between the two groups. A stepwise increase in RPP caused a slower decline and rise in RBF and RVR, respectively, in Eln +/- relative to WT mice. The maximal changes in RBF (5 ± 1.1 vs 4.7 ± 0.8 μL/min/g left kidney weight), RVR (17.6 ± 7.3 vs 22.5 ± 2.1 mmHg/μL/min/g left kidney weight), urine flow rate,GFR, and FF were less robust in Eln +/- mice. RPF decreased in WT mice in response to raising RPP, whereas it remained unchanged in Eln +/- mice. Myogenic response and increases in elastic modulus and wall tension following stepwise changes in intraluminal pressure were all augmented in interlobar arteries from Eln +/- relative to WT mice. However, there was no difference in kidney weight/tibia length ratio between the two genotypes. We conclude that elastin insufficiency impairs renal hemodynamics by exacerbating age associated increase in vascular stiffness.

Identification of a novel distension-evoked motility pattern in the mouse uterus.

The dynamic changes in uterine contractility in response to distension are incompletely understood. Rhythmic, propagating contractions of nonpregnant uterine smooth muscle occur in the absence of nerve activity (i.e., myogenic), events that decline during pregnancy and reemerge at parturition. We therefore sought to determine how myogenic contractions of the nonpregnant uterus are affected by distension, which might provide mechanistic clues underlying distension-associated uterine conditions such as preterm birth. Uteri isolated from nulliparous adult female mice in proestrus were video imaged to generate spatiotemporal maps, and myoelectrical activity simultaneously recorded using extracellular suction electrodes. Motility patterns were examined under basal conditions and following ramped intraluminal distension with fluid to 5 and 10 cmH2O. Intraluminal distension caused pressure-dependent changes in the frequency, amplitude, propagation speed, and directionality of uterine contractions, which reversed upon pressure release. Altered burst durations of underlying smooth muscle myoelectric events were concurrently observed, although action potential spike intervals were unchanged. Voltage-gated sodium channel blockade [tetrodotoxin (TTX); 0.6 µM] attenuated both the amplitude of contractions and burst duration of action potentials, whereas all activity was abolished by L-type calcium channel blockade (nifedipine; 1 µM). These data suggest that myogenic motility patterns of the nonpregnant mouse uterus are sensitive to changes in intraluminal pressure and, at high pressures, may be modulated by voltage-gated sodium channel activity. Future studies may investigate whether similar distension-evoked changes occur in the pregnant uterus and the possible pathophysiological role of such activity in the development of preterm birth.

Loss‐ and Gain‐of‐Function Mutations in the Type 1 IP3 Receptor (IP3R1) Affect Myogenic Constriction of Cerebral Resistance Arteries in Response to Intraluminal Pressure

The constriction and relaxation of resistance arteries/arterioles in response to changes in intraluminal pressure, referred to as the myogenic response, is a key physiological mechanism for the regulation of blood pressure and flow. Despite the recognized contribution of phospholipase C activity and IP3‐mediated intracellular Ca2+ release to the myogenic response, a lack of selective pharmacological agents to target the predominant IP3R1 Ca2+ release channel has prevented interrogation of this key mechanism. Mutations in the IP3R1 are known to produce either loss‐of‐function (LOF) or gain‐of‐function (GOF) phenotypes in humans that impact cerebellar activity (e.g. ataxia), yet the effect of these mutations on the cardiovascular system is not established. Here, we employed a novel genetic knock‐in mouse model with a single point mutation in the transmembrane S6 helix of IP3R1 that confers either a LOF (D2594A) or GOF (D2594K) phenotype. In preliminary experiments, the LOF and GOF mutations shifted IP3‐mediated ER Ca2+ release ~2‐fold to the right and left, respectively, compared to wild‐type (WT) IP3R1 in permeabilized HEK293 cells. In endothelium‐denuded posterior cerebral arteries of 3–4 month old WT mice, myogenic vasoconstriction was evident at ≥40 mmHg, maximal at ~120 mmHg, and declined at >120 mmHg (n=7). In contrast, myogenic constriction was initiated at a higher pressure (≥50 mmHg) and was smaller in amplitude in arteries of heterozygous IP3R1 LOF mice (n=8). In IP3R1 GOF vessels (n=7), myogenic tone developed at a lower pressure (≥20 mmHg), was maximal at ~80 mmHg, and declined at >90 mmHg. Relative levels of phosphorylation of myosin regulatory light chain (LC20) and myosin phosphatase targeting subunit (MYPT1) at 10, 40, 80 and 120 mmHg, and of globular (G‐) actin content at 10, 60 and 120 mmHg, in arteries from WT, LOF and GOF mice were assessed by ultra‐high sensitivity immunoblotting. An identical pressure‐dependent increase in phospho‐LC20 content was detected in WT, LOF and GOF vessels (n=5 each). Although phospho‐MYPT1‐T855 content increased with intraluminal pressure in arteries of WT and LOF mice, it did not change in vessels of GOF mice. Elevation of intraluminal pressure decreased in G‐actin content in arteries of WT mice, did not affect G‐actin content in LOF vessels, and caused a significantly greater decrease in GOF arteries. Taken together, these data demonstrate that genetic modification of IP3R1‐mediated Ca2+ mobilization affects the myogenic response of cerebral arteries to intraluminal pressure, a vascular impairment that may contribute to neurological dysfunction in patients with LOF and GOF IP3R1 mutations.Support or Funding InformationThis work was funded by the following research grants from the Canadian Institutes of Health Research: MOP‐97988 (WCC) MOP‐142467 (APB) and PJT‐155963 (APB, WC and WCC).

Small GTPase Cdc42 and p130 Crk‐associated substrate (p130Cas) contribute to actin cytoskeleton dynamics in the myogenic response of rat cerebral arteries to intraluminal pressure

The constriction and relaxation of cerebral resistance arteries/arterioles in response to changes in intraluminal pressure, referred to as the myogenic response, is a key physiological mechanism for the regulation of blood pressure and flow in the brain. Actin cytoskeleton dynamics in vascular smooth muscle cells involving increased actin polymerization contribute to myogenic tone development in response to pressure elevation, but our understanding of the cellular mechanisms involved is limited. Members of the Rho family of small GTPases including RhoA, Rac1 and Cdc42 are established regulators of actin cytoskeleton dynamics. RhoA‐Rho‐associated coiled‐coil kinase (ROCK)‐mediated signaling contributes to actin polymerization in the cerebral arterial myogenic response, but whether Rac1 and/or Cdc42 play a role is not known. Here, the contribution of Rac1 and Cdc42 to myogenic vasoconstriction of endothelium‐denuded posterior cerebral arteries of adult rats was assessed by pressure myography combined with ultra‐sensitive immunoblotting to quantify G‐actin content, and level of phosphorylation of myosin regulatory light chain (LC20), myosin phosphatase targeting subunit 1 (MYPT1), p130Cas, N‐WASP, Arp2, cofilin and HSP27 in the absence and presence of GTPase inhibition. Treatment of vessels with Rac1 inhibitor Ehop‐016 (2–4 μM) before or after pressurization from 10 to 80 mmHg had no effect, whereas inhibition of Cdc42 with ML‐141 (1–10 μM) suppressed myogenic tone development. Significantly, ML‐141 (10 μM) did not affect the increase in LC20 or MYPT1‐T855 phosphorylation in response to pressurization from 10 to 80 mmHg, but it completely blocked the 50% decline in G‐actin content. Pressurization increased the level of p130Cas (Y165, Y249, Y410), N‐WASP (Y256), Arp2 (T237/238), HSP27 (S82) and cofilin (S3) phosphorylation. ML‐141 blocked the increase in p130Cas, N‐WASP, Arp2 and HSP27, but not cofilin phosphorylation. In contrast, inhibition of ROCK activity with H1152 (0.3 μM), which is known to suppress MYPT1, LC20 and cofilin phosphorylation, had no effect on the level of p130Cas, N‐WASP or Arp2 phosphorylation. Pharmacological suppression of alpha5‐integrins‐, focal adhesion kinase‐, or Src kinase‐dependent signaling, that inhibit MYPT1 and LC20 phosphorylation, G‐actin reduction and myogenic tone development, also prevented the pressure‐dependent increase in p130Cas, N‐WASP, Arp2, HSP27 and cofilin phosphorylation. Taken together, these data suggest that the myogenic response of rat cerebral arteries involves Cdc42 signaling that stimulates actin cytoskeleton dynamics via a p130Cas‐, N‐WASP‐ and Arp2‐dependent mechanism. This pathway is distinct from RhoA‐ROCK signaling that increases crossbridge cycling via increased MYPT1 and LC20 phosphorylation, as well as actin dynamics via cofilin. Activation of both RhoA and Cdc42 signaling in response to pressure elevation is dependent on integrin, focal adhesion kinase and Src kinase activity.Support or Funding InformationThis work was funded by a research grant from the Canadian Institutes of Health Research MOP‐97988 (WCC).

An Animal Study of Implantation of an Esophageal Pacemaker Based on Per-Oral Endoscopic Myotomy Approach for Alleviation of Esophageal Peristalsis Disorders.

BackgroundTo restore esophageal peristalsis of achalasia patients by sequenced electric stimulation, an appropriate method must be established to implant the electrodes and pacemaker safely and effectively. We combined POEM (per-oral endoscopic myotomy) and abdominal wall puncture in pigs in order to explore a feasible procedure for the implantation.Material/MethodsFive healthy male pigs were used in the present study with the permission of the Ethics Committee of Tianjin Medical University General Hospital. The electrodes were implanted in esophageal submucosal tunnel by POEM with the end of the electrode deposited in the abdominal cavity using NOTES technique. A pacemaker was then positioned under the skin of the abdomen. Finally, the electrodes were connected with the pacemaker with the help of endoscopy in the abdominal cavity. Esophageal peristalsis of these pigs after implantation was monitored for esophageal intraluminal pressure changes using electronic gastroscopy and a high-resolution manometry (HRM). The observation lasted for 6 h.ResultsThe procedure was effective to implant the electrode and the pacemaker using POEM and NOTES techniques. The connection of the 2 devices was also successful. Esophageal intraluminal pressure changes after electrical stimulation were recorded using HRM. Vital signs of the pigs were stable during the 6-h follow-up.ConclusionsFrom this small-sample, short follow-up animal study, it was found that the implantation of esophageal electrodes and pacemaker based on POEM and NOTES is feasible, safe, and effective. Nevertheless, there is urgent need for long-term follow-up to confirm or disprove the safety of the procedure.

Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature.

Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments.NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.

Impact of Pyloric Injection of Magnesium Sulfate-Lidocaine Mixture on Postoperative Nausea and Vomiting After Laparoscopic Sleeve Gastrectomy: a Randomized-Controlled Trial.

One of the most common adverse effects of laparoscopic sleeve gastrectomy (LSG) is postoperative nausea and vomiting (PONV). The present study aimed to assess the impact of local injection of a mixture of magnesium sulfate and lidocaine into the pylorus on gastric intraluminal pressure (ILP) and PONV after LSG. Patients with morbid obesity who underwent LSG were randomly allocated to one of two equal groups: treatment group (pyloric injection of a mixture of magnesium sulfate and lidocaine) and control group (pyloric injection of normal saline). PONV and antiemetic requirements were recorded at 6 and 24h postoperatively. Seventy patients (63 female) with a mean age of 34.6 ± 9.9years were included. The mean preoperative and postoperative gastric ILP was comparable in the two groups. The pyloric injection of magnesium sulfate-lidocaine mixture resulted in 31% reduction in the mean gastric ILP (19.4 ± 4.7mmHg before injection to 13.4 ± 4.1mmHg after injection, p < 0.0001). Pyloric injection of saline did not result in significant change in ILP (19.9 ± 4.9 vs 20.3 ± 5.1mmHg). Of the treatment group patients, 17.1% had significant PONV at 6h compared to 91.4% of control group patients (p < 0.0001). At 24h, none of the treatment group patients had significant PONV versus 40% of the control group patients (p < 0.0001). Pyloric injection of magnesium sulfate-lidocaine mixture during LSG resulted in lower incidence of PONV and less use of antiemetic medications in the first 24h after LSG without being associated with higher complication rate.

Strain in the direction of stress fibers in aortic smooth muscle cells during changes in intraluminal pressure

Strain in the direction of stress fibers in aortic smooth muscle cells during changes in intraluminal pressure

Remodeling of Wall Mechanics and the Myogenic Mechanism of Rat Intramural Coronary Arterioles in Response to a Short-Term Daily Exercise Program: Role of Endothelial Factors

Purpose: Exercise elicits early adaptation of coronary vessels enabling the coronary circulation to respond adequately to higher flow demands. We hypothesized that short-term daily exercise induces biomechanical and functional remodeling of the coronary resistance arteries related to pressure. Methods: Male rats were subjected to a progressively increasing 4-week treadmill exercise program (over 60 min/day, 1 mph in the final step). In vitro pressure-diameter measurements were performed on coronary segments (119 ± 5 μm in diameter at 50 mm Hg) with microarteriography. The magnitude of the myogenic response and contribution of endogenous nitric oxide and prostanoid production to the wall mechanics and pressure-diameter relationship were assessed. Results: Arterioles isolated from exercised ani mals – compared to the sedentary group – had thicker walls, increased distensibility, and a decreased elastic modulus as a result of reduced wall stress in the low pressure range. The arterioles of exercised rats exhibited a more powerful myogenic response and less endogenous vasoconstrictor prostanoid modulation at higher pressures, while vasodilator nitric oxide modulation of diameter was augmented at low pressures (< 60 mm Hg). Conclusions: A short-term daily exercise program induces remodeling of rat intramural coronary arterioles, likely resulting in a greater range of coronary autoregulatory function (constrictor and dilator reserves) and more effective protection against great changes in intraluminal pressure, contributing thereby to the optimization of coronary blood flow during exercise.

Pushing beyond the limit: a novel clinical sign of thoracic aortic dissection

The timely diagnosis of aortic dissection is notoriously confounded by unreliable symptomatology. We present a previously unreported clinical sign: thoracic pain reproduced by abdominal palpation. Our case illustrates the dependence...

Cotransplantation of neuroepithelial stem cells with interstitial cells of Cajal improves neuronal differentiation in a rat aganglionic model

BackgroundRecent advances have raised the possibility of treating Hirschsprung's disease (HSCR) with transplanted neural stem cells. Although these cells have been shown to migrate and differentiate after transplantation, the restoration of intestinal motility by grafted cells is also mediated via the interstitial cells of Cajal (ICCs). We therefore aimed to evaluate the effect of cografting with ICC on neural stem cells after transplanted into aganglionic bowel. MethodsNeuroepithelial stem cells (NESCs) and ICCs were isolated from neural tube of embryonic rat (embryonic day 11.5) and colon of neonatal rats respectively. After cotransplantation into the benzalkonium chloride-induced rat aganglionic colon, survival and differentiation of the implanted cells were assessed 8weeks posttransplantation using immunofluorescence and Western blotting. Colonic motility was assessed by measuring the changes of intraluminal pressure responding to inflating stimulation and the response of muscle strips to electrical field stimulation. ResultsCotransplantation with ICC accelerated neuronal differentiation compared with transplantation of NESCs alone. Moreover, the contractile response to inflation and EFS-induced reaction of the colon after coimplantation were successfully evoked. ConclusionsThese data indicate that reconstitution of elements in the intestinal environment such as ICC enhances efficacy of NESCs therapy. This may aid development of a stem cell-based treatment for HSCR.

先天性食道閉鎖症術後の食道運動機能 : 第1報 臨床的検討

先天性食道閉鎖症術後の食道運動機能 : 第1報 臨床的検討

Characterization of Esophageal Physiology Using Mechanical State Analysis.

The esophagus functions to transport swallowed fluids and food from the pharynx to the stomach. The esophageal muscles governing bolus transport comprise circular striated muscle of the proximal esophagus and circular smooth muscle of the distal esophagus. Longitudinal smooth muscle contraction provides a mechanical advantage to bolus transit during circular smooth muscle contraction. Esophageal striated muscle is directly controlled by neural circuits originating in the central nervous system, resulting in coordinated contractions. In contrast, the esophageal smooth muscle is controlled by enteric circuits modulated by extrinsic central neural connections resulting in neural relaxation and contraction. The esophageal muscles are modulated by sensory information arising from within the lumen. 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 identify the “mechanical states” of the circular muscle; that is when the muscles are passively or actively, relaxing or contracting. Detecting these changes in the mechanical state of the muscle has been difficult and as the current interpretation of esophageal motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during peristalsis can be missed. We hypothesized that quantification of mechanical states of the esophageal circular muscles and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern esophageal peristalsis. To achieve this we analyzed barium swallows captured by simultaneous videofluoroscopy and 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 comparable with measurements from videofluoroscopy. Our data indicated that identification of mechanical state of esophageal muscle was simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.

Abstract TMP38: Vertebrobasilar Dolichoectasia is a Distinct Subtype of Intracranial Large Artery Disease: Computational Fluid Dynamics of Hemodynamic Abnormalities

Background: Imaging of stroke due to vertebrobasilar dolichoectasia may not reveal either luminal stenosis or atherosclerotic plaque, leading to misdiagnosis of stroke mechanism or etiology. We leveraged the advanced imaging capabilities of computational fluid dynamics (CFD) to disclose the hemodynamic abnormalities within these complex neurovascular lesions. Methods: CT angiography from a series of stroke patients with vertebrobasilar dolichoectasia was selected from a prospective imaging registry of posterior circulation ischemia. A 3D geometric mesh was generated from CTA source images, extending from distal V4 vertebral arteries (VA) to the P1 posterior cerebral arteries (PCA). CFD processing was conducted with Ansys (ICEM, CFX) on a Cray supercomputer. Boundary conditions applied at the VA inlets and PCA outlets were used to map intraluminal pressure changes (ΔP), blood flow velocities (V), turbulent kinetic energy (TKE) and wall shear stress (WSS). Results: 18 cases of vertebrobasilar dolichoectasia with CTA source images were processed with CFD. Focal stenoses (&gt;50%) were apparent in only 4/18 (22%) cases. Intraluminal pressure varied markedly throughout the vertebrobasilar arterial segments in 7/18 (39%) cases. Blood flow velocities were also heterogeneous, with increases in 6/18 (33%) cases and decreases in 5/18 (28%) cases. WSS was markedly abnormal in all 18 cases, revealing regions of both elevated WSS and contralateral decreases in WSS. Maximal TKE values were within expected range for arterial diameter, yet obvious eddy currents were visualized in all 18 cases. Conclusions: CFD generated from routine CTA reveals numerous hemodynamic abnormalities in vertebrobasilar dolichoectasia, even when stenosis is unapparent. WSS-induced remodeling mapped with CFD may be used to detect arteriogenesis and atherosclerotic lesion development.

Spatiotemporal Mapping of Motility in &lt;em&gt;Ex Vivo&lt;/em&gt; Preparations of the Intestines

Multiple approaches have been used to record and evaluate gastrointestinal motility including: recording changes in muscle tension, intraluminal pressure, and membrane potential. All of these approaches depend on measurement of activity at one or multiple locations along the gut simultaneously which are then interpreted to provide a sense of overall motility patterns. Recently, the development of video recording and spatiotemporal mapping (STmap) techniques have made it possible to observe and analyze complex patterns in ex vivo whole segments of colon and intestine. Once recorded and digitized, video records can be converted to STmaps in which the luminal diameter is converted to grayscale or color [called diameter maps (Dmaps)]. STmaps can provide data on motility direction (i.e., stationary, peristaltic, antiperistaltic), velocity, duration, frequency and strength of contractile motility patterns. Advantages of this approach include: analysis of interaction or simultaneous development of different motility patterns in different regions of the same segment, visualization of motility pattern changes over time, and analysis of how activity in one region influences activity in another region. Video recordings can be replayed with different timescales and analysis parameters so that separate STmaps and motility patterns can be analyzed in more detail. This protocol specifically details the effects of intraluminal fluid distension and intraluminal stimuli that affect motility generation. The use of luminal receptor agonists and antagonists provides mechanistic information on how specific patterns are initiated and how one pattern can be converted into another pattern. The technique is limited by the ability to only measure motility that causes changes in luminal diameter, without providing data on intraluminal pressure changes or muscle tension, and by the generation of artifacts based upon experimental setup; although, analysis methods can account for these issues. When compared to previous techniques the video recording and STmap approach provides a more comprehensive understanding of gastrointestinal motility.

Spatiotemporal Mapping of Motility in Ex Vivo Preparations of the Intestines.

Multiple approaches have been used to record and evaluate gastrointestinal motility including: recording changes in muscle tension, intraluminal pressure, and membrane potential. All of these approaches depend on measurement of activity at one or multiple locations along the gut simultaneously which are then interpreted to provide a sense of overall motility patterns. Recently, the development of video recording and spatiotemporal mapping (STmap) techniques have made it possible to observe and analyze complex patterns in ex vivo whole segments of colon and intestine. Once recorded and digitized, video records can be converted to STmaps in which the luminal diameter is converted to grayscale or color [called diameter maps (Dmaps)]. STmaps can provide data on motility direction (i.e., stationary, peristaltic, antiperistaltic), velocity, duration, frequency and strength of contractile motility patterns. Advantages of this approach include: analysis of interaction or simultaneous development of different motility patterns in different regions of the same segment, visualization of motility pattern changes over time, and analysis of how activity in one region influences activity in another region. Video recordings can be replayed with different timescales and analysis parameters so that separate STmaps and motility patterns can be analyzed in more detail. This protocol specifically details the effects of intraluminal fluid distension and intraluminal stimuli that affect motility generation. The use of luminal receptor agonists and antagonists provides mechanistic information on how specific patterns are initiated and how one pattern can be converted into another pattern. The technique is limited by the ability to only measure motility that causes changes in luminal diameter, without providing data on intraluminal pressure changes or muscle tension, and by the generation of artifacts based upon experimental setup; although, analysis methods can account for these issues. When compared to previous techniques the video recording and STmap approach provides a more comprehensive understanding of gastrointestinal motility.