Juvenile Female Pigs Research Articles

An in-silico porcine model of phosgene-induced lung injury predicts clinically relevant benefits from application of continuous positive airway pressure up to 8 h post exposure

We present the first computational model of the pathophysiological consequences of phosgene-induced lung injury in porcine subjects. Data from experiments previously performed in several cohorts of large healthy juvenile female pigs (111 data points from 37 subjects), including individual arterial blood gas readings, respiratory rate and heart rate, were used to develop the computational model. Close matches are observed between model outputs (PaO2 and PaCO2) and the experimental data, for both terminally anaesthetised and conscious subjects. The model was applied to investigate the effectiveness of continuous positive airway pressure (CPAP) as a pre-hospital treatment method when treatment is initiated at different time points post exposure. The model predicts that clinically relevant benefits are obtained when 10 cmH2O CPAP is initiated within approximately 8 h after exposure. Supplying low-flow oxygen (40%) rather than medical air produced larger clinical benefits than applying higher CPAP pressure levels. This new model can be used as a tool for conducting investigations into ventilation strategies and pharmaceutical treatments for chemical lung injury of diverse aetiology, and for helping to refine and reduce the use of animals in future experimental studies.

Colonic oxygen microbubbles augment systemic oxygenation and CO2 removal in a porcine smoke inhalation model of severe hypoxia

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury. Juvenile female Duroc pigs (n = 6 colonic OMB, n = 6 no treatment) ranging from 39 to 51 kg in weight were exposed to smoke under general anesthesia for 2 h. Animals developed severe hypoxia 48 h after smoke inhalation as reflected by reduction in SpO2 to 66.3 ± 13.1% and PaO2 to 45.3 ± 7.6 mmHg, as well as bilateral diffuse infiltrates demonstrated on chest X-ray. Colonic OMB infusion (75–100 mL/kg dose) resulted in significant improvements in systemic oxygenation as demonstrated by an increase in PaO2 of 13.2 ± 4.7 mmHg and SpO2 of 15.2 ± 10.0% out to 2.5 h, compared to no-treatment control animals that experienced a decline in PaO2 of 8.2 ± 7.9 mmHg and SpO2 of 12.9 ± 18.7% over the same timeframe. Likewise, colonic OMB decreased PaCO2 and PmvCO2 by 19.7 ± 7.6 mmHg and 7.6 ± 6.7 mmHg, respectively, compared to controls that experienced increases in PaCO2 and PmvCO2 of 17.9 ± 11.7 mmHg and 18.3 ± 11.2 mmHg. We conclude that colonic delivery of OMB therapy has potential to treat patients experiencing severe hypoxemic respiratory failure.

Comparison of Superpulse Thulium Fiber Laser vs Holmium Laser for Ablation of Renal Calculi in an In Vivo Porcine Model.

Introduction and Objectives: We sought to compare the effectiveness and efficiency of the superpulse thulium fiber laser (sTFL to the holmium: yttrium-aluminum-garnet [Ho:YAG] laser for ureteroscopic "dusting" of implanted renal stones in an in vivo porcine model. Methods: Twenty-four porcine kidneys (12 juvenile female Yorkshire pigs) were randomized to Ho:YAG or sTFL treatment groups. Canine calcium oxalate stones were scanned with computed tomography to calculate stone volume and stone density; the stones were randomized and implanted into each renal pelvis via an open pyelotomy. In all trials, a 14F, 35 cm ureteral access sheath was placed. With a 9.9F dual lumen flexible ureteroscope, laser lithotripsy was performed using dusting settings: Ho:YAG 200 μm laser fiber at 16 W (0.4 J, 40 Hz) or sTFL 200 μm laser fiber at 16 W (0.2 J, 80 Hz). Lithotripsy continued until no fragments over 1 mm were observed. No stone basketing was performed. Throughout the procedures, intrarenal and renal pelvis temperatures were measured using two percutaneously positioned K-type thermocouples, one in the upper pole calyx and one in the renal pelvis. After the lithotripsy, the ureteropelvic junction was occluded, the kidneys were bivalved, and all residual fragments were collected, dried, weighed, and then measured with an optical laser particle sizer. Results: Implanted stones were similar in volume and density in both groups. Intraoperative collecting system temperatures were similar for both groups (all <44°C). Compared to Ho:YAG, sTFL ablated stones faster (9 vs 27 minutes, p < 0.001) with less energy expenditure (8 vs 26 kJ, p < 0.001), and a greater stone clearance rate (73% vs 45%, p = 0.001). After sTFL lithotripsy, 77% of the remaining fragments were ≤1 mm vs 17% of fragments ≤1 mm after Ho:YAG treatment (p < 0.001). Conclusions: In an in vivo porcine kidney, using dusting settings, sTFL lithotripsy resulted in shorter ablation times, higher stone clearance rates, and markedly smaller stone fragments than Ho:YAG lithotripsy.

Porcine Bladder Replacement with a Bilayer Silk Fibroin Enhanced Prosthetic Reservoir: A Feasibility Study.

Introduction: The creation of synthetic reservoirs for bladder replacement has been limited by challenges of interfacing synthetic materials and native tissue. We sought to overcome this challenge by utilizing a novel bilayer silk fibroin scaffold (BLSF) as an intermediary toward the development of an acellular prosthetic reservoir. Methods: Under institutionally approved protocols, 3D-printed reservoirs were implanted in six juvenile female pigs after cystectomy. BLSF was attached to the in situ prosthetic reservoir serving as an intermediary to native ureteral and urethral tissue anastomoses. Our first protocol allowed four pigs to be survived up to 7 days, and the second protocol allowed two pigs to be survived for up to 1 year. At the first sign of functional decline or the end of the study period, the animals were euthanized, and kidneys, ureters, prosthetic bladder, and urethra were harvested en bloc for histopathology analysis. Results: The first two pigs had anastomotic urine leaks because of design flaws resulting in early termination. The third pig had acute renal failure resulting in early termination. The artificial bladder design was modified in subsequent iterations. The fourth pig survived for 7 days and, upon autopsy, had intact urethral and ureteral anastomoses. The fifth and sixth pigs survived for 11 and 12 weeks, respectively, before they were sacrificed because of failure to thrive. One animal developed an enteric fistula. The other animal had an intact anastomosis, and the BLFS was identified at the ureteral and urethral anastomoses on histopathologic analysis. Conclusions: Replacing the porcine bladder with a prosthetic bladder was achieved for up to 3 months, the second longest survival period for a nonbiologic bladder alternative. BLSF was used for the first time to create an interface between synthetic material and biologic tissue by allowing ingrowth of urothelium onto the acellular alloplastic bladder.

Generation of Porcine Ileum Through Spring-Mediated Mechanical Distraction

IntroductionShort bowel syndrome is a devastating gastrointestinal disorder in which decreased bowel length results in inadequate absorption causing nutritional deficiencies. Current treatment options are accompanied by significant morbidity. We have proposed spring-mediated distraction enterogenesis as a method to lengthen bowel with success seen in porcine jejunum. We hypothesize that spring-mediated distraction enterogenesis can be demonstrated in porcine ileum with preservation of ileal structure and function. Materials and methodsLaparotomy was performed on juvenile female mini-Yucatan pigs and a gelatin-encapsulated compressed nitinol spring was inserted into the ileal lumen and affixed proximally and distally. A control segment distal to the spring segment was marked with sutures. Postoperatively, pigs were placed on a liquid diet and euthanized on postoperative day 7. Spring and control segments were measured and processed for immunohistochemistry to evaluate for the presence of vitamin B12–intrinsic factor cotransporter, chromogranin A-producing cells, and 5-HT producing cells. ResultsAll seven pigs survived to postoperative day 7 with no adverse effects. On average, pigs gained 84.3 ± 66.4 g/d. Spring segments lengthened 1.5 ± 0.7 cm with a relative lengthening by 128% ± 56%, which was statistically significant when compared to control (P < 0.01). The average density of chromogranin-A cells in control compared to spring segments was not significantly changed (2.9 ± 1.1 cells/mm versus 3.2 ± 1.2 cells/mm, P = 0.17). Both vitamin B12–intrinsic factor cotransporter and 5-HT producing cells were present in both control and lengthened ileum. ConclusionsIntraluminal nitinol springs significantly lengthened porcine ileum. The increase in density of enteroendocrine cells may indicate enhanced endocrine function of the lengthened ileum.

Dispersal and immunohistochemical characteristics of neurons in the stem of the porcine vagus nerve.

The present study investigated the distribution and chemical properties of nerve cell bodies within the trunk of the vagus nerve in juvenile female pigs (n=4) using double-labelling immunofluorescence. The neurons appeared mostly as single cells or formed streaks of cells or small ganglia. Many of the perikarya were cholinergic (VAChT-positive; VAChT+) or adrenergic (DβH+) in nature and no SP+ or CGRP+ neurons were encountered. There were no distinct left-right differences regarding the number and chemical coding of the neuronal somata, however, these characteristics significantly varied between particular nerve segments investigated. The vagosympathetic trunks, and thoracic and abdominal segments of the vagus nerve contained on average (the numerical values represent the means for both the left and right corresponding nerve segments) 142, 236, and 111 PGP 9.5-positive neurons, respectively. Proportions of cholinergic and adrenergic neurons were as follows: 0% and 100%, 54.2% and 33.2%, and 52.8% and 35.4%, respectively. Relatively many neurons in the thoracic and abdominal segments stained also for NOS (39.2% and 39.9%, respectively). It remains to be determined whether the porcine intravagal neurons represent a developmental relic, or whether they have any specific functional significance.

The Impact of One Week of Pre-Stenting on Porcine Ureteral Luminal Circumference.

Objectives: Larger ureteral access sheaths (UASs) have the potential to improve ureteroscopic stone removal outcomes but are often avoided by surgeons because of concerns of ureteral injury. Using our novel UAS force sensor and previously defined force thresholds for ureteral injury, we sought to evaluate the impact of 1 week of stenting on the maximum safe dilation of ureteral luminal circumference. Methods: Twelve juvenile female Yorkshire pigs (24 ureters) were evaluated. The inner (i.e., luminal) circumference of each ureter was determined using Cook urethral dilators ranging from 8F to 24F in 2F increments, 37 cm in length. Each dilator was sequentially passed while applying the UAS force sensor to measure insertion force before and after 1 week of stent placement. Each ureter was randomized to receive either a 4.7F or 7.0F stent (20 cm). Maximum ureteral luminal circumference was defined as effective passage of the dilator to the ureteropelvic junction with ≤6 newtons (N) of force (the force threshold previously defined by porcine and clinical studies to avoid ureteral damage). After passage of the largest dilator at 6 N, flexible ureteroscopy was performed and a post-ureteroscopic lesion scale (PULS) was recorded. Results: After 1 week of stent placement, the median ureteral luminal circumference increased to 15F representing a mean increase of 3.8F ± 2.8F (p < 0.001). Twenty-one (88%) of the pre-stented ureters had an increase in luminal circumference, with 12 ureters (50%) dilated to ≥16F (p = 0.032), 6 ureters (25%) dilated to ≥18F, and in 2 cases a maximum size of 24F was recorded. The PULS grade was ≤2 in all cases, indicating no high-grade ureteral injuries. Laterality and stent size did not impact ureteral luminal circumference after pre-stenting (p = 0.232 and p = 0.337, respectively). Conclusions: One week of ureteral stenting resulted in nearly a 4F increase in the luminal circumference of porcine ureters.

Sexual dimorphism in ritualized agonistic behaviour, fighting ability and contest costs of Sus scrofa

BackgroundSexual selection has driven sexual dimorphism in agonistic behaviour in many species. Agonistic behaviour is fundamentally altered by domestication and captivity, but it is unclear whether ancestral sex differences remain. We aimed to evaluate the effect of sex on agonistic behaviour, fighting ability and contest costs. We studied this in domestic pigs (Sus scrofa) where aggression compromises welfare, and sexual dimorphism in aggression has been inconclusively demonstrated. Behaviour and physiology of 827 male and female juvenile pigs were studied during resident-intruder tests and dyadic contests at various ages, while accounting for the relative body weight difference between the opponents.ResultsMales won in 79% of contests against females, even when at a large weight disadvantage. The effect of sex increased with age, with males having a 138 times higher likelihood of winning than females when 13 weeks old. In dyadic contests, males invested more time in non-damaging agonistic display behaviour and took longer before escalating into damaging aggression. Males showed ritualized display that included foaming from the mouth and piloerection of the neck hair, which was nearly always absent in females. Contest costs in terms of contest duration, blood lactate and skin lesions where higher for males, especially when fighting another male.ConclusionsProfound sex differences were present for agonistic behaviour, fighting ability and contest costs, and became more pronounced as animals got older. Males invested more in ritualized display before escalating into costly fights, whereas females attacked sooner but also terminated contests more rapidly and with fewer costs. The sexual dimorphism in agonistic behaviour in juvenile domestic pigs is in line with the evolutionary relevance for females’ maternal defence and males’ competition for females.

Mechanical Power Correlates With Lung Inflammation Assessed by Positron-Emission Tomography in Experimental Acute Lung Injury in Pigs.

Background: Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP.Methods: Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[18F]fluoro-D-glucose (KiS), and its difference between the two PET/CT was calculated (ΔKiS). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure–volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation.Results: Normalized 18F-FDG uptake rate increased significantly from first to second PET/CT (p = 0.012). ΔKiS significantly correlated with median MP (ρ = 0.738, p = 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h (p = 0.012, p = 0.036, and p = 0.025, respectively). Resistance and PaCO2 were significantly higher (p = 0.012 and p = 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention.Conclusions: In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP.

PD35-11 TOTAL PORCINE BLADDER REPLACEMENT WITH AN ACELLULAR ALLOPLAST

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion I (PD35)1 Sep 2021PD35-11 TOTAL PORCINE BLADDER REPLACEMENT WITH AN ACELLULAR ALLOPLAST Pengbo Jiang, Akhil Peta, Raphael Arada, Maged Ayad, Nicholas Nguyen, Erik Larson, Krista Larson, Shlomi Tapiero, Zhamshid Okhunov, Gokhan Gundogdu, Roshan Patel, Joshua Mauney, Jaime Landman, and Ralph Clayman Pengbo JiangPengbo Jiang More articles by this author , Akhil PetaAkhil Peta More articles by this author , Raphael AradaRaphael Arada More articles by this author , Maged AyadMaged Ayad More articles by this author , Nicholas NguyenNicholas Nguyen More articles by this author , Erik LarsonErik Larson More articles by this author , Krista LarsonKrista Larson More articles by this author , Shlomi TapieroShlomi Tapiero More articles by this author , Zhamshid OkhunovZhamshid Okhunov More articles by this author , Gokhan GundogduGokhan Gundogdu More articles by this author , Roshan PatelRoshan Patel More articles by this author , Joshua MauneyJoshua Mauney More articles by this author , Jaime LandmanJaime Landman More articles by this author , and Ralph ClaymanRalph Clayman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002039.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical cystectomy and urinary diversion is the standard of treatment for patients with muscle invasive bladder cancer and intractable benign bladder conditions. There have been past efforts for bladder replacement using a completely synthetic reservoir. The major limitation of these prior studies has been the interface between the synthetic material and the native tissue. We sought to overcome this issue by utilizing a bilayer silk fibroin scaffold as the interface between tissue and the alloplast. METHODS: Following cystectomy, a three-dimensional (3-D) printed bladder reservoir was implanted in each of two juvenile female pigs. A bilayer silk fibroin scaffold (BLFS) was tubularized and attached to the artificial reservoir to serve as the intermediary to native tissue anastomoses (Figure 1). The ureters were sewn together in a Wallace fashion prior to anastomosing to the silk scaffold; 4.7Fr, 20cm ureteral stents were placed bilaterally. The urethra was anastomosed to a silk scaffold on the prosthesis; a 10Fr Cope loop was used as a urethral catheter. Postimplantation, the right and left stents were removed at 4 and 5 weeks, respectively. The pigs underwent renal ultrasonography at 2, 4, 5, 6, and then every 2 weeks and ureteroscopy at 4, 5, 6, and then every 2 weeks. The pigs will be survived until they reach 80kg, which will likely occur at 5 months. RESULTS: Currently, the animals are 6 weeks post bladder implantation. Ultrasound at 2, 4, 5, and 6 weeks showed no hydronephrosis in either pig. On cystograms and retrograde pyelograms performed at 2, 4, 5, and 6 weeks, there was no contrast extravasation. On ureteroscopic evaluation, the urethral and ureteral anastomoses were widely patent. Renal function has remained unchanged from baseline levels. CONCLUSIONS: The replacement of a porcine bladder with a totally alloplastic, acellular 3-D printed prosthesis was successfully accomplished in two pigs. At six weeks, the silk interface appears to have functioned as a successful interface between the alloplast and ureteral/urethral tissues. Source of Funding: UCI Endourology Lab - Curiosity and Innovation Fund © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e593-e594 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pengbo Jiang More articles by this author Akhil Peta More articles by this author Raphael Arada More articles by this author Maged Ayad More articles by this author Nicholas Nguyen More articles by this author Erik Larson More articles by this author Krista Larson More articles by this author Shlomi Tapiero More articles by this author Zhamshid Okhunov More articles by this author Gokhan Gundogdu More articles by this author Roshan Patel More articles by this author Joshua Mauney More articles by this author Jaime Landman More articles by this author Ralph Clayman More articles by this author Expand All Advertisement Loading ...

MP07-19 THE IMPACT OF ONE WEEK OF PRE-STENTING ON PORCINE URETERAL DIAMETER

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-19 THE IMPACT OF ONE WEEK OF PRE-STENTING ON PORCINE URETERAL DIAMETER Pengbo Jiang, Andrew Afyouni, Tori King, Samantha Dinh, Maged Ayad, Christina Kosmala, Akhil Peta, Andrew Brevik, Luke Limfuenco, Zhamshid Okhunov, Roshan Patel, Jaime Landman, and Ralph Clayman Pengbo JiangPengbo Jiang More articles by this author , Andrew AfyouniAndrew Afyouni More articles by this author , Tori KingTori King More articles by this author , Samantha DinhSamantha Dinh More articles by this author , Maged AyadMaged Ayad More articles by this author , Christina KosmalaChristina Kosmala More articles by this author , Akhil PetaAkhil Peta More articles by this author , Andrew BrevikAndrew Brevik More articles by this author , Luke LimfuencoLuke Limfuenco More articles by this author , Zhamshid OkhunovZhamshid Okhunov More articles by this author , Roshan PatelRoshan Patel More articles by this author , Jaime LandmanJaime Landman More articles by this author , and Ralph ClaymanRalph Clayman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ureteral access sheaths (UAS) are used during ureteroscopy to facilitate passage of the ureteroscope and the extraction of renal and ureteral stone fragments. Larger UAS have the potential to improve surgical outcomes, but are often avoided by surgeons due to concerns of ureteral injury. Using a novel UAS force sensor developed at our university, we sought to evaluate the impact of ureteral stent placement on ureteral circumference and the force needed to pass dilators of increasing size. METHODS: Seven juvenile female Yorkshire pigs (14 ureters) were included in the study. The inner circumference of each ureter was determined using a set of Cook urethral dilators (ranging from 8-24Fr in 2Fr increments, 37 cm in length) in combination with the UAS force sensor before and after one week of stent placement. Each ureter was randomized to receive either a 4.7 Fr or 7.0 Fr stent (20 cm in length). Maximum ureteral size was defined as successful passage of the dilator to the ureteropelvic junction at <6 Newtons (N) of force. Prior porcine and clinical studies have shown that 6N is the maximum force that can be placed on a UAS without incurring ureteral damage. Following passage of the largest dilator at 6N, flexible ureteroscopy was performed and a post-ureteroscopic lesion score (PULS) was recorded. RESULTS: After one week of stent placement, the median ureteral inner circumference increased from 12Fr to 16Fr (p <0.001). Thirteen (93%) of the 14 ureters increased in diameter following stent placement (table 1). The ureteral inner circumference recorded after stenting reached 18Fr in 36% of cases with a maximum size of 24 Fr. Right ureters had a greater increase in ureteral diameter after stenting than left ureters (p=0.005). Stent size did not have an impact on the change in ureteral diameter (p=0.573) (table 2). CONCLUSIONS: One week of ureteral stenting resulted in a 4F (1.33 mm) increase in the inner circumference (diameter) of porcine ureters. Right ureters enlarged to a greater degree than left ureters. Source of Funding: UCI Endourology Lab—Curiosity and Innovation Fund © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e147-e147 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pengbo Jiang More articles by this author Andrew Afyouni More articles by this author Tori King More articles by this author Samantha Dinh More articles by this author Maged Ayad More articles by this author Christina Kosmala More articles by this author Akhil Peta More articles by this author Andrew Brevik More articles by this author Luke Limfuenco More articles by this author Zhamshid Okhunov More articles by this author Roshan Patel More articles by this author Jaime Landman More articles by this author Ralph Clayman More articles by this author Expand All Advertisement Loading ...

Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract.

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.

The Influence of an Adrenergic Antagonist Guanethidine on the Distribution Pattern and Chemical Coding of Caudal Mesenteric Ganglion Perikarya and Their Axons Supplying the Porcine Bladder.

This study was aimed at disclosing the influence of intravesically instilled guanethidine (GUA) on the distribution, relative frequency and chemical coding of both the urinary bladder intramural sympathetic nerve fibers and their parent cell bodies in the caudal mesenteric ganglion (CaMG) in juvenile female pigs. GUA instillation led to a profound decrease in the number of perivascular nerve terminals. Furthermore, the chemical profile of the perivascular innervation within the treated bladder also distinctly changed, as most of axons became somatostatin-immunoreactive (SOM-IR), while in the control animals they were found to be neuropeptide Y (NPY)-positive. Intravesical treatment with GUA led not only to a significant decrease in the number of bladder-projecting tyrosine hydroxylase (TH) CaMG somata (94.3 ± 1.8% vs. 73.3 ± 1.4%; control vs. GUA-treated pigs), but simultaneously resulted in the rearrangement of their co-transmitters repertoire, causing a distinct decrease in the number of TH+/NPY+ (89.6 ± 0.7% vs. 27.8 ± 0.9%) cell bodies and an increase in the number of SOM-(3.6 ± 0.4% vs. 68.7 ± 1.9%), calbindin-(CB; 2.06 ± 0.2% vs. 9.1 ± 1.2%) or galanin-containing (GAL; 1.6 ± 0.3% vs. 28.2 ± 1.3%) somata. The present study provides evidence that GUA significantly modifies the sympathetic innervation of the porcine urinary bladder wall, and thus may be considered a potential tool for studying the plasticity of this subdivision of the bladder innervation.

Comparative effects of neurally adjusted ventilatory assist and variable pressure support on lung and diaphragmatic function in a model of acute respiratory distress syndrome: A randomised animal study.

Variable assisted mechanical ventilation has been shown to improve lung function and reduce lung injury. However, differences between extrinsic and intrinsic variability are unknown. To investigate the effects of neurally adjusted ventilatory assist (NAVA, intrinsic variability), variable pressure support ventilation (Noisy PSV, extrinsic variability) and conventional pressure-controlled ventilation (PCV) on lung and diaphragmatic function and damage in experimental acute respiratory distress syndrome (ARDS). Randomised controlled animal study. University Hospital Research Facility. A total of 24 juvenile female pigs. ARDS was induced by repetitive lung lavage and injurious ventilation. Animals were randomly assigned to 24 h of either: 1) NAVA, 2) Noisy PSV or 3) PCV (n=8 per group). Mechanical ventilation settings followed the ARDS Network recommendations. The primary outcome was histological lung damage. Secondary outcomes were respiratory variables and patterns, subject-ventilator asynchrony (SVA), pulmonary and diaphragmatic biomarkers, as well as diaphragmatic muscle atrophy and myosin isotypes. Global alveolar damage did not differ between groups, but NAVA resulted in less interstitial oedema in dorsal lung regions than Noisy PSV. Gas exchange and SVA incidence did not differ between groups. Compared with Noisy PSV, NAVA generated higher coefficients of variation of tidal volume and respiratory rate. During NAVA, only 40.4% of breaths were triggered by the electrical diaphragm signal. The IL-8 concentration in lung tissue was lower after NAVA compared with PCV and Noisy PSV, whereas Noisy PSV yielded lower type III procollagen mRNA expression than NAVA and PCV. Diaphragmatic muscle fibre diameters were smaller after PCV compared with assisted modes, whereas expression of myosin isotypes did not differ between groups. Noisy PSV and NAVA did not reduce global lung injury compared with PCV but affected different biomarkers and attenuated diaphragmatic atrophy. NAVA increased the respiratory variability; however, NAVA yielded a similar SVA incidence as Noisy PSV. This trial was registered and approved by the Landesdirektion Dresden, Germany (AZ 24-9168.11-1/2012-2).

In Vivo Testing of a Prototype Intradural Spinal Cord Stimulator in a Porcine Model

Chronic midline low back pain is the number one reason for disability in the United States despite the prolific use of medical and surgical interventions. Notwithstanding the widespread use of epidural spinal cord stimulators (SCSs), there remains a large portion of the population with inadequate pain control thought to be because of the limited volume of stimulated neural tissue. Intradural SCSs represent an underexplored alternative strategy with the potential to improve selectivity, power efficiency, and efficacy. We studied and carried out development of an intradural form of an SCS. Herein we present the findings of invivo testing of a prototype intradural SCS in a porcine model. Six female juvenile pigs underwent surgical investigation. One control animal underwent a laminectomy only, whereas the 5 other animals had implantation of an intradural SCS prototype. One of the prototypes was fully wired to enable acute stimulation and concurrent electromyographic recordings. All animals underwent terminal surgery 3 months postimplantation, with harvesting of the spinal column. Imaging (microcomputed tomography scan) and histopathologic examinations were subsequently performed. All animals survived implantation without evidence of neurologic deficits or infection. Postmortem imaging and histopathologic examination of the spinal column revealed no evidence of spinal cord damage, cerebrospinal fluid fistula formation, abnormal bony overgrowth, or dural defect. Viable dura was present between the intra- and extradural plates of the device. Electromyographic recordings revealed evoked motor units from the stimulator. Chronically implanted intradural device in the porcine model demonstrated safety and feasibility for translation into humans.

Ureteral Access Sheath Deployment: How Much Force Is Too Much? Initial Studies with a Novel Ureteral Access Sheath Force Sensor in the Porcine Ureter

Introduction and Objectives: Ureteral injuries can occur during ureteral access sheath (UAS) deployment. The force exerted during deployment and the amount of force that results in ureteral injury is yet to be accurately quantitated. In this feasibility study, we developed and then tested a novel force-sensing device in our animal laboratory to identify the threshold force that results in a porcine ureteral injury. Methods: With Institutional Animal Care and Use Committee approval, we measured ureteral dilator and UAS deployment force using our proprietary University of California, Irvine Ureteral Access Sheath Force Sensor (UAS-FS). The exerted force was measured during deployment from the moment that the tip of the UAS was passed into the urethral meatus until it reached the renal pelvis; progression of the UAS along the ureter was monitored with fluoroscopy. Ureteroscopic evaluation was performed after deployment of each catheter/sheath ≥8F to assess for ureteral injury using the Postureteroscopic Lesion Scale (PULS). Results: Six juvenile Yorkshire female pigs (12 ureters) were studied. No injuries were detected when the deployment force was <4 Newtons (N), which was the case when the catheter/access sheath was ≤13F. Increasing UAS size >13F resulted in greater peak forces. In five of the pigs, ureters selected for 14F UAS deployment without previous sequential dilation were injured (PULS ≥3) at a mean threshold force of 4.84 N. Serial dilation had a higher threshold for PULS ≥3 at 5.56 N. Overall, injury of PULS ≥3 was routinely noted when the force applied exceeded 8.1 N. Conclusions: The UAS-FS reliably measured forces while deploying a UAS. Significant ureteral injury can routinely be avoided if the applied force is <4.84 N; PULS ≥3 routinely occurred when forces exceeded 8.1 N. Serial dilation may allow safe passage at higher deployment forces, as much as 5.56 N.

Behavioural and cardiac responses towards different novel objects in juvenile female and male pigs (Sus scrofa)

The way in which environmental stimuli affect animals and translate into behavioural and physical responses is of high importance with regards to the animals’ well-being. The aim of the study was, to gain deeper understanding of the relationship between behavioural responses and cardiac parameters. Our study investigated the effect of eight novel objects on the behaviour and the cardiac responses of 9 female and 9 male growing pigs in postnatal weeks 6-9. The novel objects tested were a rope, a soil heap, a Kong®, an experimental glove, a dog intelligence game, a wallow, a rubber duck and a heap of leaves. Every animal was tested twice per object. During novel object tests, the exploratory behaviour towards the objects and the test environment as well as play and tail wagging behaviour were recorded. Simultaneously, heart rate (HR) and further cardiac parameters (SDNN, RMSSD, LF, HF) were measured using the Polar® System. Results show that “complex” objects (soil, wallow, leaves) were explored more than “rigid” objects (rope, glove, Kong®, IQ game, duck; p = 0.01). The novel objects tested had a significant influence on the behavioural traits, as well as the cardiac traits HR and LF (p = 0.001). In general, correlations between exploratory behaviour and cardiac parameters were not significant. We conclude from our findings that juvenile pigs have clear exploratory preferences with regards to the structure of novel objects. There was no evidence of a strong link between exploratory behaviour and cardiac responses.

Distribution and neurochemistry of porcine urinary bladder-projecting sensory neurons in subdomains of the dorsal root ganglia: A quantitative analysis

The aim of the present study has been to verify the inter- and intraganglionic distribution pattern of porcine urinary bladder-projecting (UBP) neurons localized in the sacral dorsal root ganglia (DRGs). The morphology and chemical phenotype of these cells have also been investigated. These neurons were visualized using the fluorescent tracer Fast Blue (FB) which was injected bilaterally into the urinary bladder wall of five juvenile female pigs. The intraganglionic distribution showed that small- and medium-sized FB+ perikarya were mainly located in the central (S3–S4) and periphero-central (S2) region of the ganglia, while large cells were heterogeneously distributed. Immunohistochemistry revealed that the most frequently observed markers in small and medium-sized UBP perikarya were: neurofilament 200, lectin from Bandeiraea simplicifolia (Griffonia simplicifolia) isolectin B4, substance P, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide and transient receptor potential vanilloid 1. Moreover, UBP neurons containing these substances were also mainly observed in the central and periphero-central region of the ganglion. Differences in the percentage of traced cells and their neuropeptide content were observed between the S2, S3 and S4 DRGs. In conclusion, the present study, for the first time, describes the arrangement of UBP DRGs neurons within particular subdomains of sacral ganglia, taking into account their size and chemical phenotype.

RETRACTED: Dopamine protects cerebral autoregulation and prevents hippocampal necrosis after traumatic brain injury via block of ERK MAPK in juvenile pigs

Traumatic brain injury (TBI) contributes to morbidity in children, and more boys experience TBI. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasoactive agents to increase mean arterial pressure (MAP). In prior studies of newborn and juvenile pigs, vasoactive agent choice influenced outcome after TBI as a function of age and sex, with none protecting cerebral autoregulation in both ages and sexes. Dopamine (DA) prevents impairment of cerebral autoregulation in male and female newborn pigs via inhibition of upregulation of ERK mitogen activated protein kinase (MAPK) after fluid percussion injury (FPI). We investigated whether DA protects autoregulation and limits histopathology after FPI in juvenile pigs and the role of ERK in that outcome. Results show that DA protects autoregulation in both male and female juvenile pigs after FPI. Papaverine induced dilation was unchanged by FPI and DA. DA blunted ERK MAPK and prevented loss of neurons in CA1 and CA3 hippocampus of males and females after FPI. These data indicate that DA protects autoregulation and limits hippocampal neuronal cell necrosis via block of ERK after FPI in male and female juvenile pigs. Of the vasoactive agents prior investigated, including norepinephrine, epinephrine, and phenylephrine, DA is the only one demonstrated to improve outcome after TBI in both sexes and ages. These data suggest that DA should be considered as a first line treatment to protect cerebral autoregulation and promote cerebral outcomes in pediatric TBI irrespective of age and sex.

Metabolism and pharmacokinetics of zearalenone following oral and intravenous administration in juvenile female pigs

Zearalenone (ZEN) is a well-studied mycotoxin whose potent estrogenic properties have been used by international regulatory bodies to set health-based guidance values for ZEN exposure in grain-based foods from changes in hormonally responsive tissues of juvenile female pigs. The role of metabolism in determining estrogenic responses in vivo is a major uncertainty in inter-species extrapolation to humans and in assessing the potential for added susceptibility in sensitive subpopulations. This study evaluated the metabolism of ZEN and pharmacokinetics in ∼2 month-old female pigs using oral and intravenous dosing. The absolute bioavailability (AUCoral/AUCIV) of receptor-active ZEN aglycone was 1.8 ± 0.80%, consistent with extensive pre-systemic Phase II conjugation. Reductive metabolism to α-zearalenol (α-ZEL) was extensive, with smaller amounts of β-ZEL. When combined with its higher binding affinity, relative to ZEN and β-ZEL, α-ZEL was the predominant contributor to total estrogen receptor ligand activity (∼90%) after oral dosing with ZEN. The apparent similarities of reductive and Phase II conjugation metabolism of ZEN between pigs and humans support the use of juvenile female pigs as a sensitive model for risk assessments of estrogenic effects from dietary ZEN.