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Sample records for monitored porcine model

  1. Evaluation of a Model-Based Hemodynamic Monitoring Method in a Porcine Study of Septic Shock

    PubMed Central

    Revie, James A.; Stevenson, David; Chase, J. Geoffrey; Pretty, Chris J.; Lambermont, Bernard C.; Ghuysen, Alexandre; Kolh, Philippe; Shaw, Geoffrey M.; Desaive, Thomas

    2013-01-01

    Introduction. The accuracy and clinical applicability of an improved model-based system for tracking hemodynamic changes is assessed in an animal study on septic shock. Methods. This study used cardiovascular measurements recorded during a porcine trial studying the efficacy of large-pore hemofiltration for treating septic shock. Four Pietrain pigs were instrumented and induced with septic shock. A subset of the measured data, representing clinically available measurements, was used to identify subject-specific cardiovascular models. These models were then validated against the remaining measurements. Results. The system accurately matched independent measures of left and right ventricle end diastolic volumes and maximum left and right ventricular pressures to percentage errors less than 20% (except for the 95th percentile error in maximum right ventricular pressure) and all R2 > 0.76. An average decrease of 42% in systemic resistance, a main cardiovascular consequence of septic shock, was observed 120 minutes after the infusion of the endotoxin, consistent with experimentally measured trends. Moreover, modelled temporal trends in right ventricular end systolic elastance and afterload tracked changes in corresponding experimentally derived metrics. Conclusions. These results demonstrate that this model-based method can monitor disease-dependent changes in preload, afterload, and contractility in porcine study of septic shock. PMID:23585774

  2. Porcine cancer models for translational oncology

    PubMed Central

    Sieren, Jessica C.; Quelle, Dawn; Meyerholz, David K.; Rogers, Christopher S.

    2014-01-01

    Large-animal cancer models are needed to advance the development of innovative and clinically applicable tumor diagnostic, therapeutic, and monitoring technologies. We developed a genetically modified porcine model of cancer based on a TP53 mutation, and established its utility for tracking tumorigenesis in vivo through non-invasive clinical imaging approaches. PMID:27308376

  3. Noninvasive carbon dioxide monitoring in a porcine model of acute lung injury due to smoke inhalation and burns.

    PubMed

    Belenkiy, Slava; Ivey, Katherine M; Batchinsky, Andriy I; Langer, Thomas; Necsoiu, Corina; Baker, William; Salinas, José; Cancio, Leopoldo C

    2013-06-01

    In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. Eight anesthetized Yorkshire pigs underwent mechanical ventilation, wood-bark smoke inhalation injury, and 40% total body surface area thermal injury. tPCO2 was measured with a SenTec system (SenTec AG, Therwil, Switzerland) and EtCO2 with a Capnostream-20 (Oridion Medical, Jerusalem, Israel). These values were compared with PaCO2 measurements from an arterial blood gas analyzer. Paired measurements of EtCO2-PaCO2 (n = 276) and tPCO2-PaCO2 (n = 250) were recorded in the PaCO2 range of 25 to 85 mmHg. Overlapping data sets were analyzed based on respiratory and hemodynamic status of animals. Acute lung injury was defined as PaO2/FIO2 ≤ 300 mmHg; hemodynamic instability was defined as mean arterial pressure ≤ 60 mmHg. Before ALI, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.45; P < 0.0001), which deteriorated after onset of ALI (R = 0.12; P < 0.0001). Before ALI, tPCO2 demonstrated moderate correlation (R = 0.51, P < 0.0001), which was sustained after onset of ALI (R = 0.78; P < 0.0001). During hemodynamic stability, EtCO2 demonstrated moderate correlation with PaCO2 (R = 0.44; P < 0.0001). During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under

  4. A porcine model of osteosarcoma

    PubMed Central

    Saalfrank, A; Janssen, K-P; Ravon, M; Flisikowski, K; Eser, S; Steiger, K; Flisikowska, T; Müller-Fliedner, P; Schulze, É; Brönner, C; Gnann, A; Kappe, E; Böhm, B; Schade, B; Certa, U; Saur, D; Esposito, I; Kind, A; Schnieke, A

    2016-01-01

    We previously produced pigs with a latent oncogenic TP53 mutation. Humans with TP53 germline mutations are predisposed to a wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss of p53 function has been observed in >50% of human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert to a transformed phenotype after activation of latent oncogenic TP53R167H and KRASG12D, and overexpression of MYC promotes tumorigenesis. The process mimics key molecular aspects of human sarcomagenesis. Transformed porcine MSCs exhibit genomic instability, with complex karyotypes, and develop into sarcomas on transplantation into immune-deficient mice. In pigs, heterozygous knockout of TP53 was sufficient for spontaneous osteosarcoma development in older animals, whereas homozygous TP53 knockout resulted in multiple large osteosarcomas in 7–8-month-old animals. This is the first report that engineered mutation of an endogenous tumour-suppressor gene leads to invasive cancer in pigs. Unlike in Trp53 mutant mice, osteosarcoma developed in the long bones and skull, closely recapitulating the human disease. These animals thus promise a model for juvenile osteosarcoma, a relatively uncommon but devastating disease. PMID:26974205

  5. Tissue Sampling Guides for Porcine Biomedical Models.

    PubMed

    Albl, Barbara; Haesner, Serena; Braun-Reichhart, Christina; Streckel, Elisabeth; Renner, Simone; Seeliger, Frank; Wolf, Eckhard; Wanke, Rüdiger; Blutke, Andreas

    2016-04-01

    This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. PMID:26883152

  6. Porcine models of muscular dystrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

  7. Porcine Models of Muscular Dystrophy1

    PubMed Central

    Selsby, Joshua T.; Ross, Jason W.; Nonneman, Dan; Hollinger, Katrin

    2015-01-01

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein dystrophin. This disease has been studied using a variety of animal models including fish, mice, rats, and dogs. While these models have contributed substantially to our mechanistic understanding of the disease and disease progression, limitations inherent to each model have slowed the clinical advancement of therapies, which necessitates the development of novel large-animal models. Several porcine dystrophin-deficient models have been identified, although disease severity may be so severe as to limit their potential contributions to the field. We have recently identified and completed the initial characterization of a natural porcine model of dystrophin insufficiency. Muscles from these animals display characteristic focal necrosis concomitant with decreased abundance and localization of dystrophin-glycoprotein complex components. These pigs recapitulate many of the cardinal features of muscular dystrophy, have elevated serum creatine kinase activity, and preliminarily appear to display altered locomotion. They also suffer from sudden death preceded by EKG abnormalities. Pig dystrophinopathy models could allow refinement of dosing strategies in human-sized animals in preparation for clinical trials. From an animal handling perspective, these pigs can generally be treated normally, with the understanding that acute stress can lead to sudden death. In summary, the ability to create genetically modified pig models and the serendipitous discovery of genetic disease in the swine industry has resulted in the emergence of new animal tools to facilitate the critical objective of improving the quality and length of life for boys afflicted with such a devastating disease. PMID:25991703

  8. Porcine survival model to simulate acute upper gastrointestinal bleedings.

    PubMed

    Prosst, Ruediger L; Schurr, Marc O; Schostek, Sebastian; Krautwald, Martina; Gottwald, Thomas

    2016-06-01

    The existing animal models used for the simulation of acute gastrointestinal bleedings are usually non-survival models. We developed and evaluated a new porcine model (domestic pig, German Landrace) in which the animal remains alive and survives the artificial bleeding without any cardiovascular impairment. This consists of a bleeding catheter which is implanted into the stomach, then subcutaneously tunnelled from the abdomen to the neck where it is exteriorized and fixed with sutures. Using the injection of porcine blood, controllable and reproducible acute upper gastrointestinal bleeding can be simulated while maintaining normal gastrointestinal motility and physiology. Depending on the volume of blood applied through the gastric catheter, the bleeding intensity can be varied from traces of blood to a massive haemorrhage. This porcine model could be valuable, e.g. for testing the efficacy of new bleeding diagnostics in large animals before human use. PMID:26306615

  9. LUMOR: an app for standardized control and monitoring of a porcine lung and its nutrient cycle.

    PubMed

    Lenz, Gregor; Frohner, Matthias; Sauermann, Stefan; Forjan, Mathias

    2014-01-01

    The outcome of the EU-funded project ElBik has been the lung simulator 'iLung', which imitates an actively breathing human lung with a porcine lung. In order to keep the explanted lung in a nearly physiological state during transportation from the slaughterhouse to the ventilation laboratory the tissue needs to be nourished and temperature controlled. The Project AlveoPic designs a mobile transport vehicle implementing an ISO/IEEE 11073-20601 compliant communication interface for the exchange of the physical parameters, alert messages and setpoint-values. An appropriate 11073 domain information model is designed and limitations of the defined services and attributes are identified. For monitoring purposes the Android App LUMOR is implemented providing a user with an easy-to-handle GUI. It was found, that alert capabilities and remote set features are not well supported in ISO/IEEE 11073-20601 at the moment and possible workarounds are discussed. PMID:24825688

  10. Development of a Porcine Model of Cystic Fibrosis

    PubMed Central

    Welsh, Michael J.; Rogers, Christopher S.; Stoltz, David A.; Meyerholz, David K.; Prather, Randall S.

    2009-01-01

    Cystic Fibrosis (CF) is a common autosomal recessive disease that affects multiple organs. The lack of an animal model with manifestations like those typically found in humans has slowed understanding of its pathogenesis. Therefore, because of the similarities between human and swine anatomy, biochemistry, physiology, size, and genetics, we chose to develop a porcine model of CF. We used homologous recombination in primary cultures of porcine fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced CFTR−/− pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic destruction, early focal biliary cirrhosis, and gall bladder abnormalities that were very similar to those observed in humans with CF. At birth, there were no abnormalities in the airway epithelium or submucosal glands and no evidence of inflammation, consistent with findings in the newborn human. We hope that this porcine model will help elucidate the pathogenesis of CF and thereby lead to the development of new mechanism-based therapies. PMID:19768173

  11. Development of a porcine model of cystic fibrosis.

    PubMed

    Welsh, Michael J; Rogers, Christopher S; Stoltz, David A; Meyerholz, David K; Prather, Randall S

    2009-01-01

    Cystic Fibrosis (CF) is a common autosomal recessive disease that affects multiple organs. The lack of an animal model with manifestations like those typically found in humans has slowed understanding of its pathogenesis. Therefore, because of the similarities between human and swine anatomy, biochemistry, physiology, size, and genetics, we chose to develop a porcine model of CF. We used homologous recombination in primary cultures of porcine fibroblasts to disrupt the CFTR gene and then used those cells as nuclear donors for somatic cell nuclear transfer. After crossing heterozygous pigs, we produced CFTR-/- pigs. The newborn CFTR null piglets manifested meconium ileus, pancreatic destruction, early focal biliary cirrhosis, and gall bladder abnormalities that were very similar to those observed in humans with CF. At birth, there were no abnormalities in the airway epithelium or submucosal glands and no evidence of inflammation, consistent with findings in the newborn human. We hope that this porcine model will help elucidate the pathogenesis of CF and thereby lead to the development of new mechanism-based therapies. PMID:19768173

  12. In vivo porcine training model for cranial neurosurgery.

    PubMed

    Regelsberger, Jan; Eicker, Sven; Siasios, Ioannis; Hänggi, Daniel; Kirsch, Matthias; Horn, Peter; Winkler, Peter; Signoretti, Stefano; Fountas, Kostas; Dufour, Henry; Barcia, Juan A; Sakowitz, Oliver; Westermaier, Thomas; Sabel, Michael; Heese, Oliver

    2015-01-01

    Supplemental education is desirable for neurosurgical training, and the use of human cadaver specimen and virtual reality models is routine. An in vivo porcine training model for cranial neurosurgery was introduced in 2005, and our recent experience with this unique model is outlined here. For the first time, porcine anatomy is illustrated with particular respect to neurosurgical procedures. The pros and cons of this model are described. The aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the brain and neurosurgical techniques in a mentored environment free from time constraints could be trained. Learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications. Participants were asked to evaluate the quality and utility of the programme via standardized questionnaires by a grading scale from A (best) to E (worst). In total, 154 residents have been trained on the porcine model to date. None of the participants regarded his own residency programme as structured. The bleeding and complication management (97%), the realistic laboratory set-up (89%) and the working environment (94%) were favoured by the vast majority of trainees and confirmed our previous findings. After finishing the course, the participants graded that their skills in bone drilling, dissecting the brain and preserving cerebral vessels under microscopic magnification had improved to level A and B. In vivo hands-on courses, fully equipped with microsurgical instruments, offer an outstanding training opportunity in which bleeding management on a pulsating, vital brain represents a unique training approach. Our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a complementary approach in surgical training. PMID:25240530

  13. A Porcine Pneumothorax Model for Teaching Ultrasound Diagnostics

    PubMed Central

    Oveland, Nils Petter; Sloth, Erik; Andersen, Gratien; Lossius, Hans Morten

    2012-01-01

    Objectives: Ultrasound (US) is a sensitive diagnostic tool for detecting pneumothorax (PTX), but methods are needed to optimally teach this technique outside of direct patient care. In training and research settings, porcine PTX models are sometimes used, but the description of the PTX topography in these models is lacking. The study purpose was to define the distribution of air using the reference imaging standard computed tomography (CT), to see if pleural insufflation of air into a live anaesthetized pig truly imitates a PTX in an injured patient. Methods: A unilateral catheter was inserted into one pleural cavity of each of 20 pigs, and 500 mL of air was insufflated. After a complete thoracic CT scan, the anterior, lateral, medial, basal, apical, and posterior components of the PTXs were compared. The amount of air in each location was quantified by measuring the distance from the lung edge to the chest wall (LE-CW). A supine anteroposterior chest radiograph (CXR) was taken from each model and interpreted by a senior radiologist, and the image results were compared to CT. Results: All 20 hemithoraces with PTX were correctly identified by CT, while six remained occult after interpreting the CXRs. The PTXs were anterior (100%), lateral (95%), medial (80%), basal (60%), apical (45%), and posterior (15%). The major proportion of the insufflated 500-mL volume was found in the anterior, medial, and basal recesses. Conclusions: The authors found the distribution of the intrathoracic air to be similar between a porcine model and that to be expected in human trauma patients, all having predominantly anterior PTX topographies. In a training facility, the model is easy to set up and can be scanned by the participants multiple times. To acquire the necessary skills to perform thoracic US examinations for PTX, the porcine models could be useful. PMID:22594363

  14. The porcine lung as a potential model for cystic fibrosis

    PubMed Central

    Rogers, Christopher S.; Abraham, William M.; Brogden, Kim A.; Engelhardt, John F.; Fisher, John T.; McCray, Paul B.; McLennan, Geoffrey; Meyerholz, David K.; Namati, Eman; Ostedgaard, Lynda S.; Prather, Randall S.; Sabater, Juan R.; Stoltz, David Anthony; Zabner, Joseph; Welsh, Michael J.

    2008-01-01

    Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans. In many respects, the anatomy, biochemistry, physiology, size, and genetics of pigs resemble those of humans. Thus pigs with a targeted CFTR gene might provide a good model for CF. Here, we review aspects of porcine airways and lung that are relevant to CF. PMID:18487356

  15. The porcine lung as a potential model for cystic fibrosis.

    PubMed

    Rogers, Christopher S; Abraham, William M; Brogden, Kim A; Engelhardt, John F; Fisher, John T; McCray, Paul B; McLennan, Geoffrey; Meyerholz, David K; Namati, Eman; Ostedgaard, Lynda S; Prather, Randall S; Sabater, Juan R; Stoltz, David Anthony; Zabner, Joseph; Welsh, Michael J

    2008-08-01

    Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans. In many respects, the anatomy, biochemistry, physiology, size, and genetics of pigs resemble those of humans. Thus pigs with a targeted CFTR gene might provide a good model for CF. Here, we review aspects of porcine airways and lung that are relevant to CF. PMID:18487356

  16. Development of a Consistent and Reproducible Porcine Scald Burn Model.

    PubMed

    Andrews, Christine J; Kempf, Margit; Kimble, Roy; Cuttle, Leila

    2016-01-01

    There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

  17. Use of an Ex Vivo Porcine Mucosal Model to Study Superantigen Penetration.

    PubMed

    Squier, Christopher A; Mantz, Mary J

    2016-01-01

    In vitro perfusion studies are frequently used to determine the penetration of compounds through skin and mucosa. Porcine tissue has been shown to be an excellent model for human tissue in terms of structure, function, and reactivity. We describe the use of porcine tissue ex-vivo in a continuous flow perfusion system to study the behavior of superantigens in this model. PMID:26676044

  18. MR Monitoring of Minimally Invasive Delivery of Mesenchymal Stem Cells into the Porcine Intervertebral Disc

    PubMed Central

    Barczewska, Monika; Wojtkiewicz, Joanna; Habich, Aleksandra; Janowski, Miroslaw; Adamiak, Zbigniew; Holak, Piotr; Matyjasik, Hubert; Bulte, Jeff W. M.; Maksymowicz, Wojciech; Walczak, Piotr

    2013-01-01

    Purpose Bone marrow stem cell therapy is a new, attractive therapeutic approach for treatment of intervertebral disc (IVD) degeneration; however, leakage and backflow of transplanted cells into the structures surrounding the disc may lead to the formation of undesirable osteophytes. The purpose of this study was to develop a technique for minimally invasive and accurate delivery of stem cells. Methods Porcine mesenchymal stem cells (MSCs) were labeled with superparamagnetic iron oxide nanoparticles (SPIO, Molday ION rhodamine) and first injected into the explanted swine lumbar IVD, followed by ex vivo 3T MRI. After having determined sufficient sensitivity, IVD degeneration was then induced in swine (n=3) by laser-evaporation. 3 x 106 SPIO-labeled cells embedded within hydrogel were injected in 2 doses using a transcutaneous cannula and an epidural anesthesia catheter. T2-weighted MR images were obtained at 3T before and immediately after cell infusion. Two weeks after injection, histological examination was performed for detection of transplanted cells. Results MSCs were efficiently labeled with Molday ION rhodamine. Cells could be readily detected in the injected vertebral tissue explants as distinct hypointensities with sufficient sensitivity. MR monitoring indicated that the MSCs were successfully delivered into the IVD in vivo, which was confirmed by iron-positive Prussian Blue staining of the tissue within the IVD. Conclusion We have developed a technique for non-invasive monitoring of minimally invasive stem delivery into the IVD at 3T. By using a large animal model mimicking the anatomy of IVD in humans, the present results indicate that this procedure may be clinically feasible. PMID:24058619

  19. Porcine incisional hernia model: Evaluation of biologically derived intact extracellular matrix repairs

    PubMed Central

    Delossantos, Aubrey I; Rodriguez, Neil L; Patel, Paarun; Franz, Michael G; Wagner, Christopher T

    2013-01-01

    We compared fascial wounds repaired with non-cross-linked intact porcine-derived acellular dermal matrix versus primary closure in a large-animal hernia model. Incisional hernias were created in Yucatan pigs and repaired after 3 weeks via open technique with suture-only primary closure or intraperitoneally placed porcine-derived acellular dermal matrix. Progressive changes in mechanical and biological properties of porcine-derived acellular dermal matrix and repair sites were assessed. Porcine-derived acellular dermal matrix–repaired hernias of additional animals were evaluated 2 and 4 weeks post incision to assess porcine-derived acellular dermal matrix regenerative potential and biomechanical changes. Hernias repaired with primary closure showed substantially more scarring and bone hyperplasia along the incision line. Mechanical remodeling of porcine-derived acellular dermal matrix was noted over time. Porcine-derived acellular dermal matrix elastic modulus and ultimate tensile stress were similar to fascia at 6 weeks. The biology of porcine-derived acellular dermal matrix–reinforced animals was more similar to native abdominal wall versus that with primary closure. In this study, porcine-derived acellular dermal matrix–reinforced repairs provided more complete wound healing response compared with primary closure. PMID:24555008

  20. Stent linker effect in a porcine coronary restenosis model.

    PubMed

    Park, Jun-Kyu; Lim, Kyung Seob; Bae, In-Ho; Nam, Joung-Pyo; Cho, Jae Hwa; Choi, Changyong; Nah, Jae-Woon; Jeong, Myung Ho

    2016-01-01

    In this study, we aimed to evaluate the mechanical effects of different stent linker designs on in-stent restenosis in porcine coronary arteries. We fabricated stents with an open-cell structure composed of nine main cells and three linker structures in model 1 (I-type), model 2 (S-types) and model 3 (U-types)) as well as Model 4, which is similar to a commercial bare metal stent design. The stent cells were 70 mm thick and wide, with a common symmetrical wave pattern. As the radial force increased, the number of main cells increased and the length of linker decreased. Radial force was higher in model 1, with a linear I-linker, than in models with S- or U-linkers. The flexibility measured by three-point bending showed a force of 1.09 N in model 1, 0.35 N in model 2, 0.19 N in model 3, and 0.31 N in model 4. The recoil results were similar in all models except model 4 and were related to the shape of the main cells. The foreshortening results were related to linker shape, with the lowest foreshortening observed in model 3 (U-linker). Restenosis areas in the porcine restenosis model 4 weeks after implantation were 35.4 ± 8.39% (model 1), 30.4 ± 7.56% (model 2), 40.6 ± 9.87% (model 3) and 45.1 ± 12.33% (model 4). In-stent restenosis rates measured by intravascular ultrasound (IVUS) and micro-computed tomography (micro-CT) showed similar trends as percent area stenosis measured by micro-CT. Model 2, with optimized flexibility and radial force due to its S-linker, showed significantly reduced restenosis in the animal model compared to stents with different linker designs. These results suggest that the optimal stent structure has a minimum radial force for vascular support and maximum flexibility for vascular conformability. The importance of the effects of these differences in stent design and their potential relationship with restenosis remains to be determined. PMID:26318568

  1. Laparoscopic anatrophic nephrolithotomy: feasibility study in a chronic porcine model.

    PubMed

    Kaouk, Jihad H; Gill, Inderbir S; Desai, Mihir M; Banks, Kevin L W; Raja, Shanker S; Skacel, Marek; Sung, Gyung Tak

    2003-02-01

    PURPOSE Anatrophic nephrolithotomy performed via open surgery involves incising the renal parenchyma along an avascular plane to remove a large, complex renal stone. We determined the feasibility of performing laparoscopic anatrophic nephrolithotomy in a survival porcine model. Furthermore, we present a novel technique of creating a staghorn calculus in the porcine model. MATERIALS AND METHODS After developing the technique in 3 pigs the survival study was performed in 10 consecutive animals. The procedure comprised 2 aspects. 1) We developed an animal model for staghorn calculi by retrograde injection of polyurethane (Fomo Products, Inc., Norton, Ohio) into the renal pelvis through a ureteral catheter. For a 2-week period the staghorn calculus was allowed to create hydronephrosis. 2) Laparoscopic anatrophic nephrolithotomy was done, involving control of the renal artery and vein, in situ renal hypothermia with ice slush in 1 animal, lateral renal parenchymal incision, stone extraction and suture repair of the incised collecting system and renal parenchyma. RESULTS Synthetic stone formation and laparoscopic anatrophic nephrolithotomy were successful in all 10 animals, including 1 that underwent staged bilateral anatrophic nephrolithotomy. Mean operative time for anatrophic nephrolithotomy was 125 minutes. Mean blood loss was 68 cc and mean warm ischemia time was 30 minutes (range 23 to 39). A residual small pelvicaliceal calculus was noted postoperatively in the initial 3 cases only. Thereafter, routine intraoperative ultrasonography and flexible endoscopy were done for stone localization, resulting in a stone-free rate of 100% in all 7 remaining animals. Diethylenetriamine pentaacetic acid renal scans documented improvement in the glomerular filtration rate from a mean of 26.4 ml. per minute after stone creation and hydronephrosis to 54.8 ml. per minute 4 to 5 weeks after laparoscopic anatrophic nephrolithotomy. CONCLUSIONS Laparoscopic techniques can be applied

  2. Salivary Stone Pneumatic Lithotripsy in a Live Porcine Model.

    PubMed

    Walvekar, Rohan R; Hoffman, Henry T; Kolenda, Jack; Hernandez, Stephen

    2016-06-01

    The purpose of this study is to evaluate the efficacy of endoscopic fragmentation and removal of artificial calculi in a live porcine model employing intracorporeal pneumatic lithotripsy. In this experimental study, 7 submandibular ducts were accessed and artificial calculi placed. A salivary pneumatic lithotripter probe was inserted through an interventional sialendoscope to fragment the calculi. A salivary duct catheter was then used to flush stone fragments, followed by endoscopy to assess complete fragmentation and ductal trauma. Ultimately, 7 artificial stones (3-10 mm, 4F/5F) were successfully fragmented without causing significant endoluminal trauma. Number of pulses for adequate stone fragmentation averaged 20 (range, 5-31). In all cases, stone fragments were successfully flushed out with the salivary duct catheter. Postprocedure endoscopy confirmed ductal integrity in all 7 ducts. While more studies are needed, this preliminary animal model demonstrates efficacy of endoscopic pneumatic lithotripsy for the management of sialolithiasis. PMID:27048662

  3. Emerging Technologies to Create Inducible and Genetically Defined Porcine Cancer Models

    PubMed Central

    Schook, Lawrence B.; Rund, Laurie; Begnini, Karine R.; Remião, Mariana H.; Seixas, Fabiana K.; Collares, Tiago

    2016-01-01

    There is an emerging need for new animal models that address unmet translational cancer research requirements. Transgenic porcine models provide an exceptional opportunity due to their genetic, anatomic, and physiological similarities with humans. Due to recent advances in the sequencing of domestic animal genomes and the development of new organism cloning technologies, it is now very feasible to utilize pigs as a malleable species, with similar anatomic and physiological features with humans, in which to develop cancer models. In this review, we discuss genetic modification technologies successfully used to produce porcine biomedical models, in particular the Cre-loxP System as well as major advances and perspectives the CRISPR/Cas9 System. Recent advancements in porcine tumor modeling and genome editing will bring porcine models to the forefront of translational cancer research. PMID:26973698

  4. Biphasic Presence of Fibrocytes in a Porcine Hypertrophic Scar Model

    PubMed Central

    Travis, Taryn E.; Mino, Matthew J.; Moffatt, Lauren T.; Mauskar, Neil A.; Prindeze, Nicholas J.; Ghassemi, Pejhman; Ramella-Roman, Jessica C.; Jordan, Marion H.; Shupp, Jeffrey W.

    2014-01-01

    Objective The duroc pig has been described as a promising animal model for use in the study of human wound healing and scar formation. However little is known about the presence and chronology of the fibrocyte cell population in the healing process of these animals. Methods Wounds known to form scar were created on red duroc swine (3“ × 3”) with a dermatome to a total depth of either 0.06“ or 0.09”. These wounds were allowed to heal completely and were biopsied at scheduled time points during the healing process. Biopsies were formalin-fixed and paraffin embedded for immunohistochemical analysis. Porcine-reactive antibodies to CD-45 and procollagen-1 and a human-reactive antibody to LSP-1 were used to detect the presence of fibrocytes in immunohistochemistry an immunocytochemistry. Results Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06“ deep wounds showed positive staining for CD-45 and LSP-1 within highly cellular areas at days 2 and 4 after wounding. Additional animals with 0.09” deep wounds showed positive staining within similar areas at days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining was diffuse in all samples. Cultured cells stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. Conclusions These data confirm that fibrocytes are indeed present in this porcine model. We conclude that these cells are present after initial wounding and later during scar formation and remodeling. We believe that this is evidence of a biphasic presence of fibrocytes, first as an acute response to skin wounding followed by later involvement in the remodeling process, prompted by continued inflammation in a deep partial thickness wound. PMID:25051518

  5. A Simple Porcine Model of Inducible Sustained Atrial Fibrillation.

    PubMed

    Lee, Anson M; Miller, Jacob R; Voeller, Rochus K; Zierer, Andreas; Lall, Shelly C; Schuessler, Richard B; Damiano, Ralph J; Melby, Spencer J

    2016-01-01

    The surgical management of atrial fibrillation (AF) is an evolving field with a history of testing various lesion sets and ablation technologies. Previous animal models of AF require a chronic intervention to make AF reliably inducible. Our objective was to create an acute, reliable, and reproducible porcine model of sustained AF. To accomplish this, 21 adult domestic pigs underwent median sternotomy. Methods to induce AF were then performed sequentially: manual stimulation, rapid pacing (200 beats per minute), and then rapid pacing of 8 beats with a cycle length of 300 milliseconds, followed by an extra stimulus at decreasing cycle lengths. If AF was not induced, burst pacing was performed at a cycle length of 90 milliseconds for 30 seconds. If AF was still not induced, intravenous neostigmine was administered, and the process was repeated. Atrial fibrillation was considered sustained after 1 minute. Attempts at AF induction were successful in 18 (86%) of 21. Atrial fibrillation was induced during manual stimulation in four (19%), during rapid pacing in five (24%), during burst pacing in five (24%), and after the administration of neostigmine in four (19%). Mean (SD) duration of AF was 3.6 (2.6) minutes. Of the 18, 14 (78%) reverted to sinus rhythm spontaneously and 4 (22%) required an antiarrhythmic. This technique of inducing AF can easily be used to evaluate new technologies and lesion sets without the need for creating a chronic animal model. PMID:26889882

  6. Brain microabscesses in a porcine model of Staphylococcus aureus sepsis

    PubMed Central

    2013-01-01

    Background Sepsis caused by Staphylococcus aureus often leads to brain microabscesses in humans. Animal models of haematogenous brain abscesses would be useful to study this condition in detail. Recently, we developed a model of S. aureus sepsis in pigs and here we report that brain microabscesses develop in pigs with such induced S. aureus sepsis. Twelve pigs were divided into three groups. Nine pigs received an intravenous inoculation of S. aureus once at time 0 h (group 1) or twice at time 0 h and 12 h (groups 2 and 3). In each group the fourth pig served as control. The pigs were euthanized at time 12 h (Group 1), 24 h (Group 2) and 48 h (Group 3) after the first inoculation. The brains were collected and examined histopathologically. Results All inoculated pigs developed sepsis and seven out of nine pigs developed brain microabscesses. The microabscesses contained S. aureus and were located in the prosencephalon and mesencephalon. Chorioditis and meningitis occurred from 12 h after inoculation. Conclusions Pigs with experimental S. aureus sepsis often develop brain microabscesses. The porcine brain pathology mirrors the findings in human sepsis patients. We therefore suggest the pig as a useful animal model of the development of brain microabscesses caused by S. aureus sepsis. PMID:24176029

  7. Validation of a vertical progression porcine burn model.

    PubMed

    Singer, Adam J; Hirth, Douglas; McClain, Steve A; Crawford, Laurie; Lin, Fubao; Clark, Richard A F

    2011-01-01

    A major potential goal of burn therapy is to limit progression of partial- to full-thickness burns. To better test therapies, the authors developed and validated a vertical progression porcine burn model in which partial-thickness burns treated with an occlusive dressing convert to full-thickness burns that heal with scarring and wound contraction. Forty contact burns were created on the backs and flanks of two young swine using a 150 g aluminum bar preheated to 70°C, 80°C, or 90°C for 20 or 30 seconds. The necrotic epidermis was removed and the burns were covered with a polyurethane occlusive dressing. Burns were photographed at 1, 24, and 48 hours as well as at 7, 14, 21, and 28 days postinjury. Full-thickness biopsies were obtained at 1, 4, 24, and 48 hours as well as at 7 and 28 days. The primary outcomes were presence of deep contracted scars and wound area 28 days after injury. Secondary outcomes were depth of injury, reepithelialization, and depth of scars. Data were compared across burn conditions using analysis of variance and χ(2) tests. Eight replicate burns were created with the aluminum bar using the following temperature/contact-time combinations: 70/20, 70/30, 80/20, 80/30, and 90/20. The percentage of burns healing with contracted scars were 70/20, 0%; 70/30, 25%; 80/20, 50%; 80/30, 75%; and 90/20, 100% (P = .05). Wound areas at 28 days by injury conditions were 70/20, 8.1 cm(2); 70/30, 7.8 cm(2); 80/20, 6.6 cm(2); 80/30, 4.9 cm(2); and 90/20, 4.8 cm(2) (P = .007). Depth of injury judged by depth of endothelial damage for the 80/20 and 80/30 burns at 1 hour was 36% and 60% of the dermal thickness, respectively. The depth of injury to the endothelial cells 1 hour after injury was inversely correlated with the degree of scar area (Pearson's correlation r = -.71, P < .001). Exposure of porcine skin to an aluminum bar preheated to 80°C for 20 or 30 seconds results initially in a partial-thickness burn that when treated with an occlusive dressing

  8. Cavitation-enhanced delivery of insulin in agar and porcine models of human skin.

    PubMed

    Feiszthuber, Helga; Bhatnagar, Sunali; Gyöngy, Miklós; Coussios, Constantin-C

    2015-03-21

    Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery. Fluorescently stained, soluble Actrapid insulin was placed on the surface of human skin-mimicking materials subjected to 265 kHz, 10% duty cycle focused ultrasound. A confocally and coaxially aligned 5 MHz broadband ultrasound transducer was used to detect cavitation. Two different skin models were used. The first model, 3% agar hydrogel, was insonated with a range of pressures (0.25-1.40 MPa peak rarefactional focal pressure-PRFP), with and without cavitation nuclei embedded within the agar at a concentration of 0.05% w/v. The second, porcine skin was insonated at 1.00 and 1.40 MPa PRFP. In both models, fluorescence measurements were used to determine penetration depth and concentration of delivered insulin. Results show that in agar gel, both insulin penetration depth and concentration only increased significantly in the presence of inertial cavitation, with up to a 40% enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ultrasound compared to the control samples, but there was no significant increase in penetration distance. The results underline the importance of instigating and monitoring inertial cavitation during transdermal insulin delivery. PMID:25716689

  9. Cavitation-enhanced delivery of insulin in agar and porcine models of human skin

    NASA Astrophysics Data System (ADS)

    Feiszthuber, Helga; Bhatnagar, Sunali; Gyöngy, Miklós; Coussios, Constantin-C.

    2015-03-01

    Ultrasound-assisted transdermal insulin delivery offers a less painful and less invasive alternative to subcutaneous insulin injections. However, ultrasound-based drug delivery, otherwise known as sonophoresis, is a highly variable phenomenon, in part dependent on cavitation. The aim of the current work is to investigate the role of cavitation in transdermal insulin delivery. Fluorescently stained, soluble Actrapid insulin was placed on the surface of human skin-mimicking materials subjected to 265 kHz, 10% duty cycle focused ultrasound. A confocally and coaxially aligned 5 MHz broadband ultrasound transducer was used to detect cavitation. Two different skin models were used. The first model, 3% agar hydrogel, was insonated with a range of pressures (0.25-1.40 MPa peak rarefactional focal pressure—PRFP), with and without cavitation nuclei embedded within the agar at a concentration of 0.05% w/v. The second, porcine skin was insonated at 1.00 and 1.40 MPa PRFP. In both models, fluorescence measurements were used to determine penetration depth and concentration of delivered insulin. Results show that in agar gel, both insulin penetration depth and concentration only increased significantly in the presence of inertial cavitation, with up to a 40% enhancement. In porcine skin the amount of fluorescent insulin was higher in the epidermis of those samples that were exposed to ultrasound compared to the control samples, but there was no significant increase in penetration distance. The results underline the importance of instigating and monitoring inertial cavitation during transdermal insulin delivery.

  10. Dynamic and Volumetric Variables Reliably Predict Fluid Responsiveness in a Porcine Model with Pleural Effusion

    PubMed Central

    Broch, Ole; Gruenewald, Matthias; Renner, Jochen; Meybohm, Patrick; Schöttler, Jan; Heß, Katharina; Steinfath, Markus; Bein, Berthold

    2013-01-01

    Background The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions. Methods Pigs were studied at baseline and after fluid loading with 8 ml kg−1 6% hydroxyethyl starch. After withdrawal of 8 ml kg−1 blood and induction of pleural effusion up to 50 ml kg−1 on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis. Results Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion. Conclusions In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness. PMID:23418546

  11. Feasibility and safety of endoscopic cryoablation at the duodenal papilla: Porcine model

    PubMed Central

    Yang, Dennis; Reinhard, Mary K; Wagh, Mihir S

    2015-01-01

    AIM: To assess the feasibility and safety of liquid nitrogen spray cryoablation at the duodenal papilla in a porcine model. METHODS: This prospective study protocol was approved by the University of Florida Institutional Animal Care and Use Committee. Six pigs underwent liquid nitrogen spray cryotherapy at the duodenal papilla. Freeze time of 20-s was applied per cycle (4 cycles/session). Survival animals (n = 4) were monitored for adverse events. Hemoglobin, white blood count, liver tests, and lipase were obtained at baseline and post-treatment. EGD was performed on day#7 to evaluate the papilla and for histology. All animals were euthanized and necropsy was performed at the end of the one-week survival period. Feasibility was defined as successful placement of the decompression tube in the duodenum, followed by delivery of spray cryotherapy to the duodenal papilla. Safety was determined by monitoring post-treatment blood tests and clinical course. Treatment effect was defined as endoscopic and histologic changes after cryotherapy. This was established by comparing endoscopic and histologic findings from mucosal biopsies prior to cryotherapy and on post-operative day (POD)#7. Full-thickness specimen was obtained post-mortem to assess depth of injury. RESULTS: Spray cryotherapy was feasible and successfully performed in all 6/6 (100%) animals. Cryospray with liquid nitrogen (four 20-s freeze-thaw cycles) at the duodenal papilla resulted in white frost formation at and around the target region. The mean procedural time was 54.5 min (range 50-58 min). All six animals studied had stable blood pressure, heart rate, and pulse oximetry measurements during the procedure. There were no significant intra-procedural adverse events. There were no significant differences in hemoglobin, white cell count, liver tests or lipase from baseline to post-cryotherapy. Survival animals were monitored daily post-operatively without any clinical ill effects from the cryotherapy. There was

  12. In vivo perfusion assessment of an anastomosis surgery on porcine intestinal model (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Le, Hanh N. D.; Opferman, Justin; Decker, Ryan; Cheon, Gyeong W.; Kim, Peter C. W.; Kang, Jin U.; Krieger, Axel

    2016-04-01

    Anastomosis, the connection of two structures, is a critical procedure for reconstructive surgery with over 1 million cases/year for visceral indication alone. However, complication rates such as strictures and leakage affect up to 19% of cases for colorectal anastomoses and up to 30% for visceral transplantation anastomoses. Local ischemia plays a critical role in anastomotic complications, making blood perfusion an important indicator for tissue health and predictor for healing following anastomosis. In this work, we apply a real time multispectral imaging technique to monitor impact on tissue perfusion due to varying interrupted suture spacing and suture tensions. Multispectral tissue images at 470, 540, 560, 580, 670 and 760 nm are analyzed in conjunction with an empirical model based on diffuse reflectance process to quantify the hemoglobin oxygen saturation within the suture site. The investigated tissues for anastomoses include porcine small (jejunum and ileum) and large (transverse colon) intestines. Two experiments using interrupted suturing with suture spacing of 1, 2, and 3 mm and tension levels from 0 N to 2.5 N are conducted. Tissue perfusion at 5, 10, 20 and 30 min after suturing are recorded and compared with the initial normal state. The result indicates the contrast between healthy and ischemic tissue areas and assists the determination of suturing spacing and tension. Therefore, the assessment of tissue perfusion will permit the development and intra-surgical monitoring of an optimal suture protocol during anastomosis with less complications and improved functional outcome.

  13. Experimental factors affecting in vitro absorption of six model compounds across porcine skin.

    PubMed

    Karadzovska, Daniela; Brooks, James D; Riviere, Jim E

    2012-10-01

    This comparative study evaluated the effect of several experimental variables on the absorption of six model [(14)C]-labeled compounds (caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid, and testosterone) through porcine skin. Using static and flow-through diffusion cells, finite or infinite, saturated or unsaturated doses were applied in one of three vehicles: propylene glycol, water, and ethanol following a full factorial experimental design. The flux of each compound into the receptor phase, with or without bovine serum albumin (BSA), was monitored over 24 h. Levels of radioactivity were also determined in the stratum corneum by tape stripping and in the remaining skin. Apparent permeability coefficients (Kp) and dose absorbed were calculated and compared. The overall results emphasize the importance of experimental design and confirm previous findings that identified dose volume, saturation level and vehicle as the main sources of variation in the in vitro assessment of dermal absorption, whilst diffusion cell model and the presence/absence of BSA in the receptor phase had minimal effect. Although the acquired data do not directly reveal new mechanistic information on dermal absorption, the unique and complete study design has provided a suitable data source for the development of dermal absorption prediction models. PMID:22750544

  14. Improved Cell Line IPEC-J2, Characterized as a Model for Porcine Jejunal Epithelium

    PubMed Central

    Zakrzewski, Silke S.; Richter, Jan F.; Krug, Susanne M.; Jebautzke, Britta; Lee, In-Fah M.; Rieger, Juliane; Sachtleben, Monika; Bondzio, Angelika; Schulzke, Jörg D.; Fromm, Michael; Günzel, Dorothee

    2013-01-01

    Cell lines matching the source epithelium are indispensable for investigating porcine intestinal transport and barrier properties on a subcellular or molecular level and furthermore help to reduce animal usage. The porcine jejunal cell line IPEC-J2 is established as an in vitro model for porcine infection studies but exhibits atypically high transepithelial resistances (TER) and only low active transport rates so that the effect of nutritional factors cannot be reliably investigated. This study aimed to properly remodel IPEC-J2 and then to re-characterize these cells regarding epithelial architecture, expression of barrier-relevant tight junction (TJ) proteins, adequate TER and transport function, and reaction to secretagogues. For this, IPEC-J2 monolayers were cultured on permeable supports, either under conventional (fetal bovine serum, FBS) or species-specific (porcine serum, PS) conditions. Porcine jejunal mucosa was analyzed for comparison. Main results were that under PS conditions (IPEC-J2/PS), compared to conventional FBS culture (IPEC-J2/FBS), the cell height increased 6-fold while the cell diameter was reduced by 50%. The apical cell membrane of IPEC-J2/PS exhibited typical microvilli. Most importantly, PS caused a one order of magnitude reduction of TER and of trans- and paracellular resistance, and a 2-fold increase in secretory response to forskolin when compared to FBS condition. TJ ultrastructure and appearance of TJ proteins changed dramatically in IPEC-J2/PS. Most parameters measured under PS conditions were much closer to those of typical pig jejunocytes than ever reported since the cell line’s initial establishment in 1989. In conclusion, IPEC-J2, if cultured under defined species-specific conditions, forms a suitable model for investigating porcine paracellular intestinal barrier function. PMID:24260272

  15. Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium.

    PubMed

    Zakrzewski, Silke S; Richter, Jan F; Krug, Susanne M; Jebautzke, Britta; Lee, In-Fah M; Rieger, Juliane; Sachtleben, Monika; Bondzio, Angelika; Schulzke, Jörg D; Fromm, Michael; Günzel, Dorothee

    2013-01-01

    Cell lines matching the source epithelium are indispensable for investigating porcine intestinal transport and barrier properties on a subcellular or molecular level and furthermore help to reduce animal usage. The porcine jejunal cell line IPEC-J2 is established as an in vitro model for porcine infection studies but exhibits atypically high transepithelial resistances (TER) and only low active transport rates so that the effect of nutritional factors cannot be reliably investigated. This study aimed to properly remodel IPEC-J2 and then to re-characterize these cells regarding epithelial architecture, expression of barrier-relevant tight junction (TJ) proteins, adequate TER and transport function, and reaction to secretagogues. For this, IPEC-J2 monolayers were cultured on permeable supports, either under conventional (fetal bovine serum, FBS) or species-specific (porcine serum, PS) conditions. Porcine jejunal mucosa was analyzed for comparison. Main results were that under PS conditions (IPEC-J2/PS), compared to conventional FBS culture (IPEC-J2/FBS), the cell height increased 6-fold while the cell diameter was reduced by 50%. The apical cell membrane of IPEC-J2/PS exhibited typical microvilli. Most importantly, PS caused a one order of magnitude reduction of TER and of trans- and paracellular resistance, and a 2-fold increase in secretory response to forskolin when compared to FBS condition. TJ ultrastructure and appearance of TJ proteins changed dramatically in IPEC-J2/PS. Most parameters measured under PS conditions were much closer to those of typical pig jejunocytes than ever reported since the cell line's initial establishment in 1989. In conclusion, IPEC-J2, if cultured under defined species-specific conditions, forms a suitable model for investigating porcine paracellular intestinal barrier function. PMID:24260272

  16. Met-myoglobin formation, accumulation, degradation, and myoglobin oxygenation monitoring based on multiwavelength attenuance measurement in porcine meat

    NASA Astrophysics Data System (ADS)

    Nguyen, Thien; Phan, Kien Nguyen; Lee, Jee-Bum; Kim, Jae Gwan

    2016-05-01

    We propose a simple, rapid, and nondestructive method to investigate formation, accumulation, and degradation of met-myoglobin (met-Mb) and myoglobin oxygenation from the interior of porcine meat. For the experiment, color photos and attenuance spectra of porcine meat (well-bled muscle, fat, and mixed) were collected daily to perform colorimetric analysis and to obtain the differences of attenuance between 578 and 567 nm (A578-A567) and between 615 and 630 nm (A630-A615), respectively. Oxy-, deoxy-, and met-myoglobin concentration changes over storage time were also calculated using Beer-Lamberts' law with reflectance intensities at 557, 582, and 630 nm. The change of A578-A567 was well matched with the change of myoglobin oxygenation, and the change of A630-A615 corresponded well with the formation and degradation of met-Mb. In addition, attenuation differences, A578-A567 and A630-A615, were able to show the formation of met-Mb earlier than colorimetric analysis. Therefore, the attenuance differences between wavelengths can be indicators for estimating myoglobin oxygenation and met-Mb formation, accumulation, and degradation, which enable us to design a simple device to monitor myoglobin activities in porcine meat.

  17. Evaluation of hands-on seminar for reduced port surgery using fresh porcine cadaver model

    PubMed Central

    Poudel, Saseem; Kurashima, Yo; Shichinohe, Toshiaki; Kitashiro, Shuji; Kanehira, Eiji; Hirano, Satoshi

    2016-01-01

    BACKGROUND: The use of various biological and non-biological simulators is playing an important role in training modern surgeons with laparoscopic skills. However, there have been few reports of the use of a fresh porcine cadaver model for training in laparoscopic surgical skills. The purpose of this study was to report on a surgical training seminar on reduced port surgery using a fresh cadaver porcine model and to assess its feasibility and efficacy. MATERIALS AND METHODS: The hands-on seminar had 10 fresh porcine cadaver models and two dry boxes. Each table was provided with a unique access port and devices used in reduced port surgery. Each group of 2 surgeons spent 30 min at each station, performing different tasks assisted by the instructor. The questionnaire survey was done immediately after the seminar and 8 months after the seminar. RESULTS: All the tasks were completed as planned. Both instructors and participants were highly satisfied with the seminar. There was a concern about the time allocated for the seminar. In the post-seminar survey, the participants felt that the number of reduced port surgeries performed by them had increased. CONCLUSION: The fresh cadaver porcine model requires no special animal facility and can be used for training in laparoscopic procedures. PMID:27279391

  18. Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

    PubMed Central

    Zhao, Lian-Xing; Li, Chun-Sheng; Yang, Jun; Tong, Nan; Xiao, Hong-Li; An, Le

    2016-01-01

    Background: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. Methods: This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10–15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. Results: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5–8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = −2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased

  19. Validation of subject-specific cardiovascular system models from porcine measurements.

    PubMed

    Revie, James A; Stevenson, David J; Chase, J Geoffrey; Hann, Christopher E; Lambermont, Bernard C; Ghuysen, Alexandre; Kolh, Philippe; Shaw, Geoffrey M; Heldmann, Stefan; Desaive, Thomas

    2013-02-01

    A previously validated mathematical model of the cardiovascular system (CVS) is made subject-specific using an iterative, proportional gain-based identification method. Prior works utilised a complete set of experimentally measured data that is not clinically typical or applicable. In this paper, parameters are identified using proportional gain-based control and a minimal, clinically available set of measurements. The new method makes use of several intermediary steps through identification of smaller compartmental models of CVS to reduce the number of parameters identified simultaneously and increase the convergence stability of the method. This new, clinically relevant, minimal measurement approach is validated using a porcine model of acute pulmonary embolism (APE). Trials were performed on five pigs, each inserted with three autologous blood clots of decreasing size over a period of four to five hours. All experiments were reviewed and approved by the Ethics Committee of the Medical Faculty at the University of Liege, Belgium. Continuous aortic and pulmonary artery pressures (P(ao), P(pa)) were measured along with left and right ventricle pressure and volume waveforms. Subject-specific CVS models were identified from global end diastolic volume (GEDV), stroke volume (SV), P(ao), and P(pa) measurements, with the mean volumes and maximum pressures of the left and right ventricles used to verify the accuracy of the fitted models. The inputs (GEDV, SV, P(ao), P(pa)) used in the identification process were matched by the CVS model to errors <0.5%. Prediction of the mean ventricular volumes and maximum ventricular pressures not used to fit the model compared experimental measurements to median absolute errors of 4.3% and 4.4%, which are equivalent to the measurement errors of currently used monitoring devices in the ICU (∼5-10%). These results validate the potential for implementing this approach in the intensive care unit. PMID:22126892

  20. Porcine models of digestive disease: the future of large animal translational research.

    PubMed

    Gonzalez, Liara M; Moeser, Adam J; Blikslager, Anthony T

    2015-07-01

    There is increasing interest in nonrodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia-reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine and mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

  1. Noncontact imaging of burn depth and extent in a porcine model using spatial frequency domain imaging

    PubMed Central

    Mazhar, Amaan; Saggese, Steve; Pollins, Alonda C.; Cardwell, Nancy L.; Nanney, Lillian; Cuccia, David J.

    2014-01-01

    Abstract. The standard of care for clinical assessment of burn severity and extent lacks a quantitative measurement. In this work, spatial frequency domain imaging (SFDI) was used to measure 48 thermal burns of graded severity (superficial partial, deep partial, and full thickness) in a porcine model. Functional (total hemoglobin and tissue oxygen saturation) and structural parameters (tissue scattering) derived from the SFDI measurements were monitored over 72 h for each burn type and compared to gold standard histological measurements of burn depth. Tissue oxygen saturation (stO2) and total hemoglobin (ctHbT) differentiated superficial partial thickness burns from more severe burn types after 2 and 72 h, respectively (p<0.01), but were unable to differentiate deep partial from full thickness wounds in the first 72 h. Tissue scattering parameters separated superficial burns from all burn types immediately after injury (p<0.01), and separated all three burn types from each other after 24 h (p<0.01). Tissue scattering parameters also showed a strong negative correlation to histological burn depth as measured by vimentin immunostain (r2>0.89). These results show promise for the use of SFDI-derived tissue scattering as a correlation to burn depth and the potential to assess burn depth via a combination of SFDI functional and structural parameters. PMID:25147961

  2. Vascular endothelial growth factor-A gene electrotransfer promotes angiogenesis in a porcine model of cardiac ischemia.

    PubMed

    Bulysheva, A A; Hargrave, B; Burcus, N; Lundberg, C G; Murray, L; Heller, R

    2016-08-01

    This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. Arteriograms suggest growth of new arteries as early as 2 weeks after treatment in electrotransfer animals. There is a significant reduction of infarct area and left ventricular contractility is improved in GET-treated group compared with controls. There was no significant difference in mortality of animals treated with GET of plasmid encoding VEGF-A from the control groups. Gene delivery of plasmid encoding VEGF-A to ischemic myocardium in a porcine model can be accomplished safely with potential for myocardial repair and regeneration. PMID:27078083

  3. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to characterize the infection dynamics and pathogenicity of two heterologous type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a conventional pig model under the influence of concurrent porcine circovirus (PCV) subtype 2a or 2b infection. ...

  4. A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains

    PubMed Central

    Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M.; van Baarlen, Peter

    2016-01-01

    Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID:26999052

  5. A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains.

    PubMed

    Zaccaria, Edoardo; Cao, Rui; Wells, Jerry M; van Baarlen, Peter

    2016-01-01

    Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the ΔciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID:26999052

  6. Cell Sheet Transplantation for Esophageal Stricture Prevention after Endoscopic Submucosal Dissection in a Porcine Model

    PubMed Central

    Pidial, Laetitia; Camilleri, Sophie; Bellucci, Alexandre; Casanova, Amaury; Viel, Thomas; Tavitian, Bertrand; Cellier, Christophe; Clement, Olivier

    2016-01-01

    Background & Aims Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. Methods Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. Results One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6(17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). Conclusion In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture’s rate. PMID:26930409

  7. Porcine gonadogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five images submitted for teaching purposes related to porcine gonadogenesis (2), porcine fetal testicular development (2), and porcine fetal ovarian development. Key words include: Egg cell nests, Embryo, GATA4, Genital ridge, Gonad, Leydig cell, Mesonephros, MIS, Ovary, P450c17, Porcine, Sertoli ...

  8. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

    PubMed Central

    Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong; Li, Yongqin

    2015-01-01

    Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

  9. Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models

    PubMed Central

    Gibly, Romie F.; Zhang, Xiaomin; Graham, Melanie L.; Hering, Bernhard J.; Kaufman, Dixon B.; Lowe, William L.; Shea, Lonnie D.

    2011-01-01

    Intraportal transplantation of islets has successfully treated select patients with type 1 diabetes. However, intravascular infusion and the intrahepatic site contribute to significant early and late islet loss, yet a clinical alternative has remained elusive. We investigated non-encapsulating, porous, biodegradable polymer scaffolds as a vehicle for islet transplantation into extrahepatic sites, using syngeneic mouse and allogeneic porcine models. Scaffold architecture was modified to enhance cell infiltration leading to re-vascularization of the islets with minimal inflammatory response. In the diabetic mouse model, 125 islets seeded on scaffolds implanted into the epididymal fat pad restored normoglycemia within an average of 1.95 days and transplantation of only 75 islets required 12.1 days. Increasing the pore size to increase islet-islet interactions did not significantly impact islet function. The porcine model was used to investigate early islet engraftment. Increasing the islet seeding density led to a greater mass of engrafted islets, though the efficiency of islet survival decreased. Transplantation into the porcine omentum provided greater islet engraftment than the gastric submucosa. These results demonstrate scaffolds support murine islet transplantation with high efficiency, and feasibility studies in large animals support continued pre-clinical studies with scaffolds as a platform to control the transplant microenvironment. PMID:21959005

  10. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells

    PubMed Central

    Di Lauro, Salvatore; Rodriguez-Crespo, David; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, J. Carlos; Srivastava, Girish K.

    2016-01-01

    Purpose To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. Methods RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. Results Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. Conclusions A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies. PMID:27081295

  11. Shear mechanical properties of the porcine pancreas: experiment and analytical modelling.

    PubMed

    Nicolle, S; Noguer, L; Palierne, J-F

    2013-10-01

    We provide the first account of the shear mechanical properties of porcine pancreas using a rheometer both in linear oscillatory tests and in constant strain-rate tests reaching the non-linear sub-failure regime. Our results show that pancreas has a low and weakly frequency-dependent dynamic modulus and experiences a noticeable strain-hardening beyond 20% strain. In both linear and non-linear regime, the viscoelastic behaviour of porcine pancreas follows a four-parameter bi-power model that has been validated on kidney, liver and spleen. Among the four solid organs of the abdomen, pancreas proves to be the most compliant and the most viscous one. PMID:23820244

  12. Structural investigation of porcine stomach mucin by X-ray fiber diffraction and homology modeling

    SciTech Connect

    Veluraja, K.; Vennila, K.N.; Umamakeshvari, K.; Jasmine, A.; Velmurugan, D.

    2011-03-25

    Research highlights: {yields} Techniques to get oriented mucin fibre. {yields} X-ray fibre diffraction pattern for mucin. {yields} Molecular modeling of mucin based on X-ray fibre diffraction pattern. -- Abstract: The basic understanding of the three dimensional structure of mucin is essential to understand its physiological function. Technology has been developed to achieve orientated porcine stomach mucin molecules. X-ray fiber diffraction of partially orientated porcine stomach mucin molecules show d-spacing signals at 2.99, 4.06, 4.22, 4.7, 5.37 and 6.5 A. The high intense d-spacing signal at 4.22 A is attributed to the antiparallel {beta}-sheet structure identified in the fraction of the homology modeled mucin molecule (amino acid residues 800-980) using Nidogen-Laminin complex structure as a template. The X-ray fiber diffraction signal at 6.5 A reveals partial organization of oligosaccharides in porcine stomach mucin. This partial structure of mucin will be helpful in establishing a three dimensional structure for the whole mucin molecule.

  13. ENDOSCOPIC HIGH-INTENSITY FOCUSED US: TECHNICAL ASPECTS AND STUDIES IN AN IN VIVO PORCINE MODEL

    PubMed Central

    Li, Tong; Khokhlova, Tatiana; Wang, Yak-Nam; Maloney, Ezekiel; D'Andrea, Samantha; Starr, Frank; Farr, Navid; Morrison, Kyle; Keilman, George; Hwang, Joo Ha

    2015-01-01

    Background High-intensity focused ultrasound (HIFU) is becoming more widely used for non-invasive and minimally invasive ablation of benign and malignant tumors. Recent studies suggest that HIFU can also enhance targeted drug delivery and stimulate an anti-tumor immune response in many tumors. However, targeting of pancreatic and liver tumors using an extracorporeal source is challenging due to the lack of an adequate acoustic window. The development of an endoscopic ultrasound (EUS)-guided HIFU transducer has many potential benefits including improved targeting, decreased energy requirements and decreased potential for injury to intervening structures. Objective To design, develop and test an EUS-guided HIFU transducer for endoscopic applications. Design A pre-clinical, pilot characterization and feasibility study. Setting Academic research center. Patients Studies were performed in an in vivo porcine model. Intervention Thermal ablation of in vivo porcine pancreas and liver was performed with EUS guided focused ultrasound through the gastric tract. Results The transducer successfully created lesions in gel phantoms and ex vivo bovine livers. In vivo studies demonstrated that targeting and creating lesions in the porcine pancreas and liver are feasible. Limitations This is a pre-clinical, single-center feasibility study with a limited number of subjects. Conclusion An EUS-guided HIFU transducer was successfully designed and developed with dimensions that are appropriate for endoscopic use. Feasibility of performing EUS-guided HIFU ablation in vivo has been demonstrated in an in vivo porcine model. Further development of this technology will allow endoscopists to perform precise therapeutic ablation of peri-lumenal lesions without breaching the wall of the gastric tract. PMID:25759124

  14. Small-Incision Laparoscopy-Assisted Surgery Under Abdominal Cavity Irrigation in a Porcine Model

    PubMed Central

    Ishii, Takuro; Aoe, Tomohiko; Yu, Wen-Wei; Ebihara, Yuma; Kawahira, Hiroshi; Isono, Shiro; Naya, Yukio

    2016-01-01

    Abstract Background: Laparoscopic and robot-assisted surgeries are performed under carbon dioxide insufflation. Switching from gas to an isotonic irrigant introduces several benefits and avoids some adverse effects of gas insufflation. We developed an irrigating device and apparatus designed for single-incision laparoscopic surgery and tested its advantages and drawbacks during surgery in a porcine model. Materials and Methods: Six pigs underwent surgical procedures under general anesthesia. A 30-cm extracorporeal cistern was placed over a 5–6-cm abdominal incision. The abdomen was irrigated with warm saline that was drained via a suction tube placed near the surgical field and continuously recirculated through a closed circuit equipped with a hemodialyzer as a filter. Irrigant samples from two pigs were cultured to check for bacterial and fungal contamination. Body weight was measured before and after surgery in four pigs that had not received treatments affecting hemodynamics or causing diuresis. Results: One-way flow of irrigant ensured laparoscopic vision by rinsing blood from the surgical field. Through a retroperitoneal approach, cystoprostatectomy was successfully performed in three pigs, nephrectomy in two, renal excision in two, and partial nephrectomy in one, under simultaneous ultrasonographic monitoring. Through a transperitoneal approach, liver excision and hemostasis with a bipolar sealing device were performed in three pigs, and bladder pedicle excision was performed in one pig. Bacterial and fungal contamination of the irrigant was observed on the draining side of the circuit, but the filter captured the contaminants. Body weight increased by a median of 2.1% (range, 1.2–4.4%) of initial weight after 3–5 hours of irrigation. Conclusions: Surgery under irrigation is feasible and practical when performed via a cistern through a small abdominal incision. This method is advantageous, especially in the enabling of continuous and free

  15. Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson's disease.

    PubMed

    Harrower, T P; Tyers, P; Hooks, Y; Barker, R A

    2006-01-01

    Porcine fetal neural tissue has been considered as an alternative source to human allografts for transplantation in neurodegenerative disorders by virtue of the fact that it can overcome the ethical and practical difficulties using human fetal neural tissue. However, primary porcine neural xenografts are rejected while porcine expanded neural precursor neural cells (PNPCs) seem to be less immunogenic and thus survive better [Armstrong, R.J., Harrower, T.P., Hurelbrink, C.B., McLaughin, M., Ratcliffe, E.L., Tyers, P., Richards, A., Dunnett, S.B., Rosser, A.E., Barker, R.A., 2001a. Porcine neural xenografts in the immunocompetent rat: immune response following grafting of expanded neural precursor cells. Neuroscience 106, 201-216]. In this study, we extended these observations to investigate the long-term survival of such transplants in immunosuppressed rats. Unilateral 6 OHDA lesioned rats received grafts into the dopamine denervated striatum of either primary porcine fetal neural tissue dissected from the E26 cortex or cortically derived neural stem cells which had been derived from the same source but expanded in vitro for 21 days. All cortically derived neural stem cell grafts survived up to 5 months in contrast to the poor survival of primary porcine xenografts. Histological analysis demonstrated good graft integration with fibers extending into the surrounding host tissue including white matter with synapse formation, and in addition there was evidence of host vascularization and myelinated fibers within the graft area. This study has therefore shown for the first time the reliable long-term survival of grafts derived from porcine expanded neural precursors in a rat model of PD, with maturation and integration into the host brain. This demonstrates that such xenografted cells may be able to recreate the damaged circuitry in PD although strategies for dopaminergic differentiation of the porcine neural precursor cell remain to be refined. PMID:16246328

  16. Creating a model of diseased artery damage and failure from healthy porcine aorta.

    PubMed

    Noble, Christopher; Smulders, Nicole; Green, Nicola H; Lewis, Roger; Carré, Matt J; Franklin, Steve E; MacNeil, Sheila; Taylor, Zeike A

    2016-07-01

    Large quantities of diseased tissue are required in the research and development of new generations of medical devices, for example for use in physical testing. However, these are difficult to obtain. In contrast, porcine arteries are readily available as they are regarded as waste. Therefore, reliable means of creating from porcine tissue physical models of diseased human tissue that emulate well the associated mechanical changes would be valuable. To this end, we studied the effect on mechanical response of treating porcine thoracic aorta with collagenase, elastase and glutaraldehyde. The alterations in mechanical and failure properties were assessed via uniaxial tension testing. A constitutive model composed of the Gasser-Ogden-Holzapfel model, for elastic response, and a continuum damage model, for the failure, was also employed to provide a further basis for comparison (Calvo and Peña, 2006; Gasser et al., 2006). For the concentrations used here it was found that: collagenase treated samples showed decreased fracture stress in the axial direction only; elastase treated samples showed increased fracture stress in the circumferential direction only; and glutaraldehyde samples showed no change in either direction. With respect to the proposed constitutive model, both collagenase and elastase had a strong effect on the fibre-related terms. The model more closely captured the tissue response in the circumferential direction, due to the smoother and sharper transition from damage initiation to complete failure in this direction. Finally, comparison of the results with those of tensile tests on diseased tissues suggests that these treatments indeed provide a basis for creation of physical models of diseased arteries. PMID:26945437

  17. A model of security monitoring

    NASA Technical Reports Server (NTRS)

    Bishop, Matt

    1990-01-01

    A model of security monitoring is presented that distinguishes between two types of logging and auditing. Implications for the design and use of security monitoring mechanisms are drawn from this model. The usefulness of the model is then demonstrated by analyzing several different monitoring mechanisms.

  18. A model of security monitoring

    NASA Technical Reports Server (NTRS)

    Bishop, Matt

    1989-01-01

    A model of security monitoring is presented that distinguishes between two types of logging and auditing. Implications for the design and use of security monitoring mechanisms are drawn from this model. The usefulness of the model is then demonstrated by analyzing several different monitoring mechanisms.

  19. Novel technique for full-thickness resection of gastric malignancy: feasibility of nonexposed endoscopic wall-inversion surgery (news) in porcine models.

    PubMed

    Mitsui, Takashi; Goto, Osamu; Shimizu, Nobuyuki; Hatao, Fumihiko; Wada, Ikuo; Niimi, Keiko; Asada-Hirayama, Itsuko; Fujishiro, Mitsuihiro; Koike, Kazuhiko; Seto, Yasuyuki

    2013-12-01

    Full-thickness resection for gastric malignancy carries a risk of peritoneal dissemination due to opening of the gastric lumen. We evaluated the feasibility and safety a novel method of full-thickness resection without transmural communication, called nonexposed endoscopic wall-inversion surgery in ex vivo and in vivo porcine models. Six explanted porcine stomachs and 6 live pigs were used for this study. After marking and submucosal injection around 3 cm simulated lesions, the seromuscular layer was laparoscopically cut and sutured with the lesion inverted to the inside. Consecutively, a mucosubmucosal incision was made endoscopically. Three pigs used for the survival study were monitored for 7 days. All 12 lesions were successfully resected en bloc without perforation. The 3 pigs survived for 1 week without adverse events, and necropsy revealed neither leakage nor abscess formation related to the operation. We demonstrated nonexposed endoscopic wall-inversion surgery to be technically feasible and safe in both ex vivo and in vivo porcine studies. PMID:24300935

  20. Material Properties and Constitutive Modeling of Infant Porcine Cerebellum Tissue in Tension at High Strain Rate

    PubMed Central

    Li, Kui; Zhao, Hui; Liu, Wenjun; Yin, Zhiyong

    2015-01-01

    Background The mechanical characterization of infant porcine cerebellum tissue in tension at high strain rate is crucial for modeling traumatic cerebellum injury, which is in turn helpful for understanding the biomechanics of such injuries suffered in traffic accidents. Material and Method In this study, the infant porcine cerebellum tissue was given three loading velocities, ie, 2s-1, 20s-1 and 100s-1 with up to 30% strain to investigate the tensile properties. At least six tensile tests for each strain rate were validly performed. Fung, Gent, Ogden and exponential models were applied to fit the constitutive equations, so as to obtain material parameters from the experimental data. Results The Lagrange stress of infant porcine cerebellum tissue in tension appeared to be no more than 3000Pa at each loading velocity. More specifically, the Lagrange stress at 30% strain was (393.7±84.4)Pa, (928.3±56.3)Pa and (2582.4±282.2)Pa at strain rates of 2s-1, 20s-1 and 100s-1, respectively. Fung (0.833≤R2≤0.924), Gent (0.797≤R2≤0.875), Ogden (0.859≤R2≤0.944) and exponential (0.930≤R2≤0.972) models provided excellent fitting to experimental data up to 30% strain. Conclusions The infant cerebellum tissue shows a stiffer response with increase of the loading speed, indicating a strong strain-rate sensitivity. This study will enrich the knowledge on the material properties of infant brain tissue, which may augment the biofidelity of finite element model of human pediatric cerebellum. PMID:25830545

  1. Porcine models of digestive disease: the future of large animal translational research

    PubMed Central

    Gonzalez, Liara M.; Moeser, Adam J.; Blikslager, Anthony T.

    2015-01-01

    There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

  2. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  3. Robot-Assisted Pterygium Surgery: Feasibility Study in a Nonliving Porcine Model

    PubMed Central

    Bourcier, Tristan; Nardin, Mathieu; Sauer, Arnaud; Gaucher, David; Speeg, Claude; Mutter, Didier; Marescaux, Jacques; Liverneaux, Philippe

    2015-01-01

    Purpose This study aims to investigate the feasibility of pterygium surgery using the DaVinci Si HD robotic surgical system, and to describe a porcine model for pterygium surgery and evaluate its usefulness. Methods The pterygium models were constructed using enucleated pig eyes and cold cuts. Robotically-assisted pterygium surgeries in nonliving biological pterygium models were performed using the DaVinci Si HD robotic surgical system. Twelve models were prepared, and 12 pterygium excision and conjunctival autografts were performed. Results The DaVinci system provided the necessary dexterity to perform delicate ocular surface surgery and robotic tools were safe for the tissues. The mean duration of the surgical procedures was 36 minutes. There were no intraoperative complications and no unexpected events. Conclusions Robotic-assisted pterygium surgery is technically feasible for porcine eyes using the DaVinci Si HD robotic surgical system. The pterygium model that we describe could be of interest for surgical training. Translational Relevance Little research has been done in robotic microsurgery. Animal experimentation will allow the advantages of robotic-assisted microsurgery to be identified, while underlining the improvements and innovations necessary for clinical use. PMID:25722953

  4. Constitutive Modeling of Porcine Liver in Indentation Using 3D Ultrasound Imaging

    PubMed Central

    Jordan, P.; Socrate, S.; Zickler, T.E.; Howe, R.D.

    2009-01-01

    In this work we present an inverse finite-element modeling framework for constitutive modeling and parameter estimation of soft tissues using full-field volumetric deformation data obtained from 3D ultrasound. The finite-element model is coupled to full-field visual measurements by regularization springs attached at nodal locations. The free ends of the springs are displaced according to the locally estimated tissue motion and the normalized potential energy stored in all springs serves as a measure of model-experiment agreement for material parameter optimization. We demonstrate good accuracy of estimated parameters and consistent convergence properties on synthetically generated data. We present constitutive model selection and parameter estimation for perfused porcine liver in indentation and demonstrate that a quasilinear viscoelastic model with shear modulus relaxation offers good model-experiment agreement in terms of indenter displacement (0.19 mm RMS error) and tissue displacement field (0.97 mm RMS error). PMID:19627823

  5. Porcine cadaver iris model for iris heating during corneal surgery with a femtosecond laser

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Fan, Zhongwei; Wang, Jiang; Yan, Ying; Juhasz, Tibor; Kurtz, Ron

    2015-03-01

    Multiple femtosecond lasers have now been cleared for use for ophthalmic surgery, including for creation of corneal flaps in LASIK surgery. Preliminary study indicated that during typical surgical use, laser energy may pass beyond the cornea with potential effects on the iris. As a model for laser exposure of the iris during femtosecond corneal surgery, we simulated the temperature rise in porcine cadaver iris during direct illumination by the femtosecond laser. Additionally, ex-vivo iris heating due to femtosecond laser irradiation was measured with an infrared thermal camera (Fluke corp. Everett, WA) as a validation of the simulation.

  6. Mesenchymal stem cells preserve neonatal right ventricular function in a porcine model of pressure overload.

    PubMed

    Wehman, Brody; Sharma, Sudhish; Pietris, Nicholas; Mishra, Rachana; Siddiqui, Osama T; Bigham, Grace; Li, Tieluo; Aiello, Emily; Murthi, Sarah; Pittenger, Mark; Griffith, Bartley; Kaushal, Sunjay

    2016-06-01

    Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, β-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic

  7. In vivo porcine left atrial wall stress: Computational model.

    PubMed

    Di Martino, Elena S; Bellini, Chiara; Schwartzman, David S

    2011-10-13

    Most computational models of the heart have so far concentrated on the study of the left ventricle, mainly using simplified geometries. The same approach cannot be adopted to model the left atrium, whose irregular shape does not allow morphological simplifications. In addition, the deformation of the left atrium during the cardiac cycle strongly depends on the interaction with its surrounding structures. We present a procedure to generate a comprehensive computational model of the left atrium, including physiological loads (blood pressure), boundary conditions (pericardium, pulmonary veins and mitral valve annulus movement) and mechanical properties based on planar biaxial experiments. The model was able to accurately reproduce the in vivo dynamics of the left atrium during the passive portion of the cardiac cycle. A shift in time between the peak pressure and the maximum displacement of the mitral valve annulus allows the appendage to inflate and bend towards the ventricle before the pulling effect associated with the ventricle contraction takes place. The ventricular systole creates room for further expansion of the appendage, which gets in close contact with the pericardium. The temporal evolution of the volume in the atrial cavity as predicted by the finite element simulation matches the volume changes obtained from CT scans. The stress field computed at each time point shows remarkable spatial heterogeneity. In particular, high stress concentration occurs along the appendage rim and in the region surrounding the pulmonary veins. PMID:21907340

  8. ULTRASOUND-ENHANCED rt-PA THROMBOLYSIS IN AN EX VIVO PORCINE CAROTID ARTERY MODEL

    PubMed Central

    Hitchcock, Kathryn E.; Ivancevich, Nikolas M.; Haworth, Kevin J.; Caudell Stamper, Danielle N.; Vela, Deborah C.; Sutton, Jonathan T.; Pyne-Geithman, Gail J.; Holland, Christy K.

    2014-01-01

    Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 μg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 μL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model. PMID:21723448

  9. Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model.

    PubMed

    Schwartz, R S; Huber, K C; Murphy, J G; Edwards, W D; Camrud, A R; Vlietstra, R E; Holmes, D R

    1992-02-01

    Restenosis is a reparative response to arterial injury occurring with percutaneous coronary revascularization. However, the quantitative characteristics of the relation between vessel injury and the magnitude of restenotic response remain unknown. This study was thus performed to determine the relation between severity of vessel wall injury and the thickness of resulting neointimal proliferation in a porcine model of coronary restenosis. Twenty-six porcine coronary artery segments in 24 pigs were subjected to deep arterial injury with use of overexpanded, percutaneously delivered tantalum wire coils. The vessels were studied microscopically 4 weeks after coil implantation to measure the relation between the extent of injury and the resulting neointimal thickness. For each wire site, a histopathologic score proportional to injury depth and the neointimal thicknesses at that site were determined. Mean injury scores were compared with both mean neointimal thickness and planimetry-derived area percent lumen stenosis. The severity of vessel injury strongly correlated with neointimal thickness and percent diameter stenosis (p less than 0.001). Neointimal proliferation resulting from a given wire was related to injury severity in adjacent wires, suggesting an interaction among effects at injured sites. If the results in this model apply to human coronary arteries, restenosis may depend on the degree of vessel injury sustained during angioplasty. PMID:1732351

  10. Porcine retinal cell line VIDO R1 and Chlamydia suis to modelize ocular chlamydiosis.

    PubMed

    Käser, Tobias; Cnudde, Thomas; Hamonic, Glenn; Rieder, Meghanne; Pasternak, J Alex; Lai, Ken; Tikoo, Suresh K; Wilson, Heather L; Meurens, François

    2015-08-15

    Human ocular Chlamydia trachomatis infections can lead to trachoma, the major cause of infectious blindness worldwide. Trachoma control strategies are very helpful but logistically challenging, and a trachoma vaccine is needed but not available. Pigs are a valuable large animal model for various immunological questions and could facilitate the study of human ocular chlamydial infections. In addition, a recent study identified the zoonotic potential of Chlamydia suis, the natural pathogen of pigs. In terms of the One Health Initiative, understanding the host-pathogen-interactions and finding a vaccine for porcine chlamydia infections would also benefit human health. Thus, we infected the porcine retinal cell line VIDO R1 with C. suis and analyzed the chlamydial life cycle and the innate immune response of the infected cells. Our results indicate that C. suis completes its life cycle in VIDO R1 cells within 48 h, comparable to C. trachomatis in humans. C. suis infection of VIDO R1 cells led to increased levels of various innate immune mediators like pathogen recognition receptors, cytokines and chemokines including IL6, TNFα, and MMP9, also most relevant in human C. trachomatis infections. These results illustrate the first steps in the host-pathogen-interactions of ocular C. suis infections in pigs and show their similarity to C. trachomatis infections in humans, justifying further testing of pigs as an animal model for human trachoma. PMID:26103808

  11. A novel device to create consistent deep dermal burns in a porcine model

    PubMed Central

    Menon, Seema; Chan, Queenie; Bertinetti, Monique; Harvey, John G; Hei, Erik R La; Holland, Andrew JA

    2016-01-01

    We conducted this study to evaluate a novel device to create a consistent and reproducible deep partial thickness burn in a porcine model. A thermostatically controlled, heated aluminium disc device was fashioned by the Biomedical Department of our institution. Contact burns were made on the flank of two Great White pigs by applying the device heated to 92°C at intervals of 5, 10, 15 and 20 seconds to four separate test areas area of skin. Biopsies for histological analysis of burn depth were taken on day 0 at 10 minutes post burn and on day 8. Biopsies taken at day 0 revealed superficial to mid-dermal burns, with minimal dermal edema and necrosis. Those from day 8 showed mid to deep dermal edema and necrosis in all four test areas following a 20 second contact duration burn. The new contact burn device was able to create a consistent deep dermal burn after 20 seconds of contact. We anticipate that this new device could be used to investigate the development of hypertrophic scarring in a porcine model. PMID:27335694

  12. Laparoscopic colonic anastomosis using a degradable stent in a porcine model

    PubMed Central

    Ma, Liang; Cai, Xiu-Jun; Wang, Hai-Hong; Yu, Yan-Lan; Huang, Di-Yu; Ge, Guang-Ju; Hu, Hai-Yi; Yu, Shi-Cheng

    2016-01-01

    AIM: To explore the feasibility and safety of laparoscopic colonic anastomosis using a degradable stent in a porcine model. METHODS: Twenty Bama mini-pigs were randomly assigned to a stent group (n = 10) and control group (hand-sewn anastomosis, n = 10). The anastomotic completion and operation times were recorded, along with histological examination, postoperative general condition, complications, mortality, bursting pressure, and the average anastomotic circumference (AC). RESULTS: All pigs survived postoperatively except for one in the stent group that died from ileus at 11 wk postoperatively. The operation and anastomotic completion times of the stent group were significantly shorter than those of the control group (P = 0.004 and P = 0.001, respectively). There were no significant differences in bursting pressure between the groups (P = 0.751). No obvious difference was found between the AC and normal circumference in the stent group, but AC was significantly less than normal circumference in the control group (P = 0.047, P < 0.05). No intestinal leakage and luminal stenosis occurred in the stent group. Histological examination revealed that the stent group presented with lower general inflammation and better healing. CONCLUSION: Laparoscopic colonic anastomosis with a degradable stent is a simple, rapid, and safe procedure in this porcine model. PMID:27217702

  13. Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

    PubMed Central

    Weuster, Matthias; Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; van Griensven, Martijn; Witte, Ingo

    2015-01-01

    Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

  14. Porcine aortic organ culture: a model to study the cellular response to vascular injury.

    PubMed

    Gotlieb, A I; Boden, P

    1984-07-01

    Organ cultures of porcine thoracic aorta were studied to define the characteristics of this system as a model to study the reaction of endothelial cells (ECs) and the underlying smooth muscle cells (SMCs) to injury. Both nonwounded and wounded cultures, the latter having had part of the endothelial surface gently denuded with a scalpel blade, were studied over a 7 d period by scanning and transmission electron microscopy. The results showed that the nonwounded ECs underwent a shape change from elongated to polygonal within 24 h in culture. In both nonwounded and wounded explants there was cell proliferation beneath the nondenuded endothelium so that by 7 d several layers of cells were present showing features of the secretory type of SMCs. This proliferation, however, did not occur if the endothelium was totally removed from the aorta. There was also evidence of gaps between the surface ECs, and by 7 d lamellipodia of cells beneath the surface were present in these gaps. Occasionally, elongated cells were seen to be present on the surface of the endothelium. In the wounded organ culture, cell migration and proliferation occurred extending from the wound edge and producing a covering of cells on the denuded area. There were also multilayered cells beneath the surface similar to the nonwounded area. Occasional foam cells were seen in the depth of the multilayered proliferating cells. The results indicate that organ culture of porcine thoracic aorta is a good model to study the reaction of ECs and underlying SMCs to injury. PMID:6469272

  15. Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

    PubMed

    Schnürer, C; Hager, M; Györi, G; Velik-Salchner, C; Moser, P L; Laufer, G; Lorenz, I H; Kolbitsch, C

    2011-02-01

    In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model. PMID:21224818

  16. Ventricular Arrhythmias and Mortality Associated with Isoflurane and Sevoflurane in a Porcine Model of Myocardial Infarction

    PubMed Central

    Regueiro-Purriños, Marta; Fernández-Vázquez, Felipe; de Prado, Armando Perez; Altónaga, Jose R; Cuellas-Ramón, Carlos; Ajenjo-Silverio, Jose M; Orden, Asuncion; Gonzalo-Orden, Jose M

    2011-01-01

    Ischemia of the myocardium can lead to reversible or irreversible injury depending on the severity and duration of the preceding ischemia. Here we compared sevoflurane and isoflurane with particular reference to their hemodynamic effects and ability to modify the effects of acute severe myocardial ischemia and reperfusion on ventricular arrhythmias and mortality in a porcine model of myocardial infarction. Female Large White pigs were premedicated with ketamine, midazolam, and atropine. Propofol was given intravenously for the anesthetic induction, and anesthesia was maintained with isoflurane or sevoflurane. Endovascular, fluoroscopy-guided, coronary procedures were performed to occlude the midleft anterior descending artery by using a coronary angioplasty balloon. After 75 min, the balloon catheter system was withdrawn and the presence of adequate reperfusion flow was verified. The pigs were followed for 2 mo, and overall mortality rate was calculated. The isoflurane group showed lower arterial pressure throughout the procedure, with the difference reaching statistical significance after induction of myocardial ischemia. The ventricular fibrillation rate was higher in isoflurane group (81.3%) than the sevoflurane group (51.7%; relative risk, 1.57 [1.03 to 2.4]). Overall survival was lower in the isoflurane group (75%) than the sevoflurane group (96.4%). In conclusion, in this porcine model of myocardial ischemia and reperfusion, sevoflurane was associated with higher hemodynamic stability and fewer ventricular arrhythmias and mortality than was isoflurane. PMID:21333167

  17. A porcine model of full-thickness burn, excision and skin autografting

    PubMed Central

    Branski, Ludwik K.; Mittermayr, Rainer; Herndon, David N.; Norbury, William B.; Masters, Oscar E.; Hofmann, Martina; Traber, Daniel L.; Redl, Heinz; Jeschke, Marc G.

    2008-01-01

    Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization. Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring. The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality. PMID:18617332

  18. Sinus Hypoplasia Precedes Sinus Infection in a Porcine Model of Cystic Fibrosis

    PubMed Central

    Chang, Eugene H; Pezzulo, Alejandro A; Meyerholz, David K; Potash, Andrea E; Wallen, Tanner J; Reznikov, Leah R; Sieren, Jessica C; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; McCray, Paul B; Stoltz, David A; Welsh, Michael J; Zabner, Joseph

    2012-01-01

    Objectives/Hypothesis Chronic sinusitis is nearly universal in humans with cystic fibrosis (CF) and is accompanied by sinus hypoplasia (small sinuses). However, whether impaired sinus development is a primary feature of loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or a secondary consequence of chronic infection remains unknown. Our objective was to study the early pathogenesis of sinus disease in CF. Study Design Animal/basic science research. Methods Sinus development was studied in a porcine CF model. Results Porcine sinus epithelia expressed CFTR and exhibited transepithelial anion transport. Disruption of the CFTR gene eliminated both. Sinuses of newborn CF pigs were not infected and showed no evidence of inflammation, yet were hypoplastic at birth. Older CF pigs spontaneously developed sinus disease similar to that seen in humans with CF. Conclusions These results define a role for CFTR in sinus development and suggest the potential of the CF pig as a genetic model of CF-sinus disease in which to test therapeutic strategies to minimize sinus-related CF morbidity. PMID:22711071

  19. Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis

    PubMed Central

    Fleury, Agnès; Trejo, Armando; Cisneros, Humberto; García-Navarrete, Roberto; Villalobos, Nelly; Hernández, Marisela; Villeda Hernández, Juana; Hernández, Beatriz; Rosas, Gabriela; Bobes, Raul J.; S. de Aluja, Aline; Sciutto, Edda; Fragoso, Gladis

    2015-01-01

    Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 oncospheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments. PMID:26252878

  20. Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis.

    PubMed

    Fleury, Agnès; Trejo, Armando; Cisneros, Humberto; García-Navarrete, Roberto; Villalobos, Nelly; Hernández, Marisela; Villeda Hernández, Juana; Hernández, Beatriz; Rosas, Gabriela; Bobes, Raul J; de Aluja, Aline S; Sciutto, Edda; Fragoso, Gladis

    2015-01-01

    Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum antibodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 oncospheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflammatory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflammatory approaches and it should improve the management of severe NC patients, refractory to the current treatments. PMID:26252878

  1. [The isolated perfused porcine kidney model for investigations concerning surgical therapy procedures].

    PubMed

    Peters, Kristina; Michel, Maurice Stephan; Matis, Ulrike; Häcker, Axel

    2006-01-01

    Experiments to develop innovative surgical therapy procedures are conventionally conducted on animals, as crucial aspects like tissue removal and bleeding disposition cannot be investigated in vitro. Extracorporeal organ models however reflect these aspects and could thus reduce the use of animals for this purpose fundamentally in the future. The aim of this work was to validate the isolated perfused porcine kidney model with regard to its use for surgical purposes on the basis of histological and radiological procedures. The results show that neither storage nor artificial perfusion led to any structural or functional damage which would affect the quality of the organ. The kidney model is highly suitable for simulating the main aspects of renal physiology and allows a constant calibration of perfusion pressure and tissue temperature. Thus, with only a moderate amount of work involved, the kidney model provides a cheap and readily available alternative to conventional animal experiments; it allows standardised experimental settings and provides valid results. PMID:17086351

  2. Immunohistochemistry of porcine skin.

    PubMed

    Wollina, U; Berger, U; Mahrle, G

    1991-01-01

    The present paper reports immunohistological findings in porcine skin, which were obtained by use of mono- and polyclonal antihuman antibodies and either alkaline phosphatase anti-alkaline phosphatase (APAAP) or peroxidase (POX) technique. Epidermal staining was observed with antibodies to keratins (K 8.12, RSKE 60), filaggrin, and calmodulin (ACAM). Staining of connective tissue and vessels was achieved using antibodies to vimentin (V9(1)), collagen type IV, and fibronectin. In general, these antibodies gave a staining pattern similar to that of normal human skin. The similarities of immunoreactivity to poly- and monoclonal antihuman antibodies in porcine and human skin render porcine skin a reliable model in biomedical research. PMID:1710864

  3. Percentile growth charts for biomedical studies using a porcine model.

    PubMed

    Corson, A M; Laws, J; Laws, A; Litten, J C; Lean, I J; Clarke, L

    2008-12-01

    Increasing rates of obesity and heart disease are compromising quality of life for a growing number of people. There is much research linking adult disease with the growth and development both in utero and during the first year of life. The pig is an ideal model for studying the origins of developmental programming. The objective of this paper was to construct percentile growth curves for the pig for use in biomedical studies. The body weight (BW) of pigs was recorded from birth to 150 days of age and their crown-to-rump length was measured over the neonatal period to enable the ponderal index (PI; kg/m3) to be calculated. Data were normalised and percentile curves were constructed using Cole's lambda-mu-sigma (LMS) method for BW and PI. The construction of these percentile charts for use in biomedical research will allow a more detailed and precise tracking of growth and development of individual pigs under experimental conditions. PMID:22444086

  4. Novel A20-gene-eluting stent inhibits carotid artery restenosis in a porcine model

    PubMed Central

    Zhou, Zhen-hua; Peng, Jing; Meng, Zhao-you; Chen, Lin; Huang, Jia-Lu; Huang, He-qing; Li, Li; Zeng, Wen; Wei, Yong; Zhu, Chu-Hong; Chen, Kang-Ning

    2016-01-01

    Background Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model. Materials and methods The pCDNA3.1EHA20 was firmly attached onto stents that had been collagen coated and treated with N-succinimidyl-3-(2-pyridyldithiol)propionate solution and anti-DNA immunoglobulin fixation. Anti-restenosis effects of modified vs control (the bare-metal stent and pCDNA3.1 void vector) stents were assessed by Western blot and scanning electron microscopy, as well as by morphological and inflammatory reaction analyses. Results Stent-delivered A20 gene was locally expressed in porcine carotids in association with significantly greater extent of re-endothelialization at day 14 and of neointimal hyperplasia inhibition at 3 months than stenting without A20 gene expression. Conclusion The A20-gene-eluting stent inhibits neointimal hyperplasia while promoting re-endothelialization and therefore constitutes a novel potential alternative to prevent restenosis while minimizing complications. PMID:27540277

  5. Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol

    PubMed Central

    Kaths, J. Moritz; Echeverri, Juan; Goldaracena, Nicolas; Louis, Kristine S.; Yip, Paul; John, Rohan; Mucsi, Istvan; Ghanekar, Anand; Bagli, Darius; Selzner, Markus; Robinson, Lisa A.

    2016-01-01

    Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication. PMID

  6. Heterotopic Renal Autotransplantation in a Porcine Model: A Step-by-Step Protocol.

    PubMed

    Kaths, J Moritz; Echeverri, Juan; Goldaracena, Nicolas; Louis, Kristine S; Yip, Paul; John, Rohan; Mucsi, Istvan; Ghanekar, Anand; Bagli, Darius; Selzner, Markus; Robinson, Lisa A

    2016-01-01

    Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration. Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication. PMID

  7. A porcine model of early atrial fibrillation using a custom-built, radio transmission-controlled pacemaker.

    PubMed

    Schwarzl, Michael; Alogna, Alessio; Zweiker, David; Verderber, Jochen; Huber, Stefan; Manninger, Martin; Scherr, Daniel; Antoons, Gudrun; Pieske, Burkert M; Post, Heiner; Lueger, Andreas

    2016-01-01

    Mechanisms underlying atrial remodeling toward atrial fibrillation (AF) are incompletely understood. We induced AF in 16 pigs by 6weeks of rapid atrial pacing (RAP, 600bpm) using a custom-built, telemetrically controlled pacemaker. AF evolution was monitored three times per week telemetrically in unstressed, conscious animals. We established a dose-response relationship between RAP duration and occurrence of sustained AF >60minutes. Left atrial (LA) dilatation was present already at 2weeks of RAP. There was no evidence of left ventricular heart failure after 6weeks of RAP. As a proof-of-principle, arterial hypertension was induced in 5/16 animals by implanting desoxycorticosterone acetate (DOCA, an aldosterone-analog) subcutaneously to accelerate atrial remodeling. RAP+DOCA resulted in increased AF stability with earlier onset of sustained AF and accelerated anatomical atrial remodeling with more pronounced LA dilatation. This novel porcine model can serve to characterize effects of maladaptive stimuli or protective interventions specifically during early AF. PMID:26803554

  8. In vivo tissue response following implantation of shape memory polyurethane foam in a porcine aneurysm model

    PubMed Central

    Rodriguez, Jennifer N.; Clubb, Fred J.; Wilson, Thomas S.; Miller, Matthew W.; Fossum, Theresa W.; Hartman, Jonathan; Tuzun, Egemen; Singhal, Pooja; Maitland, Duncan J.

    2014-01-01

    Cerebral aneurysms treated by traditional endovascular methods using platinum coils have a tendency to be unstable, either due to chronic inflammation, compaction of coils, or growth of the aneurysm. We propose to use alternate filling methods for the treatment of intracranial aneurysms using polyurethane based shape memory polymer (SMP) foams. SMP polyurethane foams were surgically implanted in a porcine aneurysm model to determine biocompatibility, localized thrombogenicity, and their ability to serve as a stable filler material within an aneurysm. The degree of healing was evaluated via gross observation, histopathology and low vacuum scanning electron microscopy (LV-SEM) imaging after zero, thirty and ninety days. Clotting was initiated within the SMP foam at time zero (less than one hour exposure to blood prior to euthanization), partial healing was observed at thirty days, and almost complete healing had occurred at ninety days in vivo, with minimal inflammatory response. PMID:23650278

  9. A retrospective review of burn dressings on a porcine burn model.

    PubMed

    Wang, Xue-Qing; Kravchuk, Olena; Kimble, Roy M

    2010-08-01

    This is a study to compare wound healing among three types of dressings on a porcine model with deep-dermal-partial-thickness burns. The burns in this study were from eight animal trials conducted in the past for other purposes and only burns with a uniform pale appearance that had served as controls in original experiments were selected. In total, there were 57 burns in 33 pigs, using one of following three dressings: Acticoat (Silver) (3 trials), Jelonet (Gauze) (3 trials), and Solosite Gel/Jelonet (Gel/Gauze) (2 trials). The wound healing assessments included wound re-epithelialisation during a 6-week period, clinical and histological scar assessments at week 6 after burn. Of all wound healing/scar assessments, only re-epithelialisation showed statistical difference between dressings. Earlier re-epithelialisation was observed in Gel/Gauze dressings compared to Silver and/or Gauze dressings. However, this study revealed huge variation in wound healing outcome between 3 trials within both Silver and/or Gauze dressings, supported by significant differences on re-epithelialisation, clinical and histological scar measurements. In addition, it was found that larger animals healed better than smaller ones, based on weights from 21 pigs. Of all dressings, Silver delivers the best protection for wound colonization/infection. Wound colonization/infection was found to confine wound healing and lead to thinner RND in scars. From this study, we cannot find enough evidence to suggest the beneficial effect of one dressing(s) over others on burn wound healing outcome on a porcine model with small deep-dermal-partial-thickness burns with a relative small sample size. PMID:19864074

  10. Vascular histopathologic reaction to pulmonary artery banding in an in vivo growing porcine model.

    PubMed

    Nedorost, Lukáš; Uemura, Hideki; Furck, Anke; Saeed, Imran; Slavik, Zdenek; Kobr, Jiří; Tonar, Zbyněk

    2013-10-01

    Pulmonary artery banding (PAB) is used as a surgical palliation to reduce excessive pulmonary blood flow caused by congenital heart defects. Due to the lack of microscopic studies dealing with the tissue remodeling caused by contemporary PAB materials, this study aimed to assess histologic changes associated with PAB surgery by analyzing local tissue reaction to the presence of Gore-Tex strips fixed around the pulmonary artery. Gore-Tex strips were used for PAB in a growing porcine model. After 5 weeks, histologic samples with PAB (n = 5) were compared with healthy pulmonary arterial segments distal to the PAB or from a sham-treated animal (n = 1). Stereology was used to quantify the density of the vasa vasorum and the area fraction of elastin, smooth muscle actin, macrophages, and nervi vasorum within the pulmonary arterial wall. The null hypothesis stated that samples did not differ histopathologically from adjacent vascular segments or sham-treated samples. The PAB samples had a greater area fraction of macrophages, a lower amount of nervi vasorum, and a tendency toward decreased smooth muscle content compared with samples that had no PAB strips. There was no destruction of elastic membranes, no medionecrosis, no pronounced inflammatory infiltration or foreign body reaction, and no vasa vasorum deficiency after the PAB. All the histopathologic changes were limited to the banded vascular segment and did not affect distal parts of the pulmonary artery. The study results show the tissue reaction of palliative PAB and suggest that Gore-Tex strips used contemporarily for PAB do not cause severe local histologic damage to the banded segment of the pulmonary arterial wall after 5 weeks in a porcine PAB model. PMID:23591800

  11. Bovine Serum Albumin Glutaraldehyde for Completely Sutureless Laparoscopic Heminephrectomy in a Survival Porcine Model

    PubMed Central

    Gamboa, Aldrin Joseph R.; Kaplan, Adam G.; Khosravi, Amanda; Truong, Hung; Andrade, Lorena; Lin, Rachelle; Alipanah, Reza; Ortiz, Cervando; McCormick, David; Box, Geoffrey N.; Lee, Hak J.; Deane, Leslie A.; Edwards, Robert A.; McDougall, Elspeth M.; Clayman, Ralph V.

    2010-01-01

    Abstract Introduction Laparoscopic partial nephrectomy (LPN) has not received widespread clinical application because of its technical challenge. Bovine serum albumin glutaraldehyde (BSAG) is a hemostatic agent that is independent of the clotting cascade. We evaluated the use of BSAG as the sole agent for parenchymal and collecting system closure during LPN in a survival porcine model. Methods Eighteen pigs underwent hilar clamping and LPN by longitudinal excision of the lateral one-third of the right kidney. The opened collecting system was covered with oxidized cellulose to prevent BSAG seepage into the urinary tract. BSAG was allowed to set for 10 or 5 minutes. Twelve animals underwent survival LPN BSAG only closure; six control pigs were acutely studied using saline. Urinary extravasation was evaluated by injection of furosemide and indigo carmine, and then evaluating the renal surface and bladder catheter drainage for dye. A subjective bleeding score was assigned after hilum unclamping. At 6 weeks, BSAG kidneys were harvested for burst pressure testing and histopathological analysis. Results All 12 pigs survived for 6 weeks. No pigs had urinary extravasation. Mean percentage of kidney removed by weight was 19%. Mean warm ischemia time was 29 minutes. Five pigs required a second BSAG application to achieve a bleeding score of 0. Mean arterial and collecting system burst pressures were 301.8 and 322.4 mm Hg, respectively. Mean postoperative creatinine increase was 0.07 mg/dL. Conclusion BSAG for completely sutureless LPN in a survival porcine model was feasible. PMID:20059350

  12. Histologic Characterization of Acellular Dermal Matrices in a Porcine Model of Tissue Expander Breast Reconstruction

    PubMed Central

    Carruthers, Christopher A.; Dearth, Christopher L.; Reing, Janet E.; Kramer, Caroline R.; Gagne, Darcy H.; Crapo, Peter M.; Garcia, Onelio; Badhwar, Amit; Scott, Jeffrey R.

    2015-01-01

    Background: Acellular dermal matrices (ADMs) have been commonly used in expander-based breast reconstruction to provide inferolateral prosthesis coverage. Although the clinical performance of these biologic scaffold materials varies depending on a number of factors, an in-depth systematic characterization of the host response is yet to be performed. The present study evaluates the biochemical composition and structure of two ADMs, AlloDerm® Regenerative Tissue Matrix and AlloMax™ Surgical Graft, and provides a comprehensive spatiotemporal characterization in a porcine model of tissue expander breast reconstruction. Methods: Each ADM was characterized with regard to thickness, permeability, donor nucleic acid content, (residual double-stranded DNA [dsDNA]), and growth factors (basic fibroblast growth factor [bFGF], vascular endothelial growth factor [VEGF], and transforming growth factor-beta 1 [TGF-β1]). Cytocompatibility was evaluated by in vitro cell culture on the ADMs. The host response was evaluated at 4 and 12 weeks at various locations within the ADMs using established metrics of the inflammatory and tissue remodeling response: cell infiltration, multinucleate giant cell formation, extent of ADM remodeling, and neovascularization. Results: AlloMax incorporated more readily with surrounding host tissue as measured by earlier and greater cell infiltration, fewer foreign body giant cells, and faster remodeling of ADM. These findings correlated with the in vitro composition and cytocompatibility analysis, which showed AlloMax to more readily support in vitro cell growth. Conclusions: AlloMax and AlloDerm demonstrated distinct remodeling characteristics in a porcine model of tissue expander breast reconstruction. PMID:24941900

  13. Endoscopic spray cryotherapy for genitourinary malignancies: safety and efficacy in a porcine model

    PubMed Central

    Power, Nicholas E.; Silberstein, Jonathan L.; Tarin, Tatum; Au, Joyce; Thorner, Daniel; Ezell, Paula; Monette, Sébastien; Fong, Yuman; Rusch, Valerie; Finley, David

    2013-01-01

    Objective: To examine the effects and safety of using endoscopic spray cryotherapy (ESC) on bladder, ureteral, and renal pelvis urothelium in a live porcine model. Subjects and methods: ESC treatments were systematically applied to urothelial sites in the bladder, ureter, and renal pelvis of eight female Yorkshire swine in a prospective trial. Freeze–thaw cycles ranged from 5 to 60 s/cycle for one to six cycles using a 7 French cryotherapy catheter. Tissue was evaluated histologically for treatment-related effects. Acute physiologic effects were evaluated with pulse oximetry, Doppler sonography, and postmortem findings. Results: In bladder, treatment depth was inconsistent regardless of dose, demonstrating urothelial necrosis in one, muscularis propria depth necrosis in two, and full thickness necrosis in all remaining samples. In ureter, full thickness necrosis was seen in all samples, even with the shortest spray duration (5 s/cycle for six cycles or 30 s/cycle for one cycle). Treatment to the renal pelvis was complicated by adiabatic gas expansion of liquid nitrogen to its gaseous state, resulting in high intraluminal pressures requiring venting to avoid organ perforation, even at the lowest treatment settings. At a planned dose of 5 s/cycle for six cycles of the first renal pelvis animal, treatment was interrupted by sudden and unrecoverable cardiopulmonary failure after three cycles. Repeated studies replicated this event. Ultrasound and immediate necropsy confirmed the creation of a large gaseous embolism and reproducible cardiopulmonary effects. Conclusion: ESC in a porcine urothelial treatment model results in full-thickness tissue necrosis in bladder, ureter, and renal pelvis at a minimal treatment settings of 5 s/cycle for six cycles. Adiabatic gas expansion may result in fatal pyelovenous gas embolism and collateral organ injury, as seen in both animals receiving treatment to the renal pelvis in this study. These results raise safety concerns for use

  14. Experimental validation of a new biphasic model of the contact mechanics of the porcine hip

    PubMed Central

    Wang, Qianqian; Jin, Zhongmin; Williams, Sophie; Fisher, John; Wilcox, Ruth K

    2014-01-01

    Hip models that incorporate the biphasic behaviour of articular cartilage can improve understanding of the joint function, pathology of joint degeneration and effect of potential interventions. The aim of this study was to develop a specimen-specific biphasic finite element model of a porcine acetabulum incorporating a biphasic representation of the articular cartilage and to validate the model predictions against direct experimental measurements of the contact area in the same specimen. Additionally, the effect of using a different tension–compression behaviour for the solid phase of the articular cartilage was investigated. The model represented different radial clearances and load magnitudes. The comparison of the finite element predictions and the experimental measurement showed good agreement in the location, size and shape of the contact area, and a similar trend in the relationship between contact area and load was observed. There was, however, a deviation of over 30% in the magnitude of the contact area, which might be due to experimental limitations or to simplifications in the material constitutive relationships used. In comparison with the isotropic solid phase model, the tension–compression solid phase model had better agreement with the experimental observations. The findings provide some confidence that the new biphasic methodology for modelling the cartilage is able to predict the contact mechanics of the hip joint. The validation provides a foundation for future subject-specific studies of the human hip using a biphasic cartilage model. PMID:24878736

  15. Monitoring Survivability and Infectivity of Porcine Epidemic Diarrhea Virus (PEDv) in the Infected On-Farm Earthen Manure Storages (EMS)

    PubMed Central

    Tun, Hein M.; Cai, Zhangbin; Khafipour, Ehsan

    2016-01-01

    In recent years, porcine epidemic diarrhea virus (PEDv) has caused major epidemics, which has been a burden to North America’s swine industry. Low infectious dose and high viability in the environment are major challenges in eradication of this virus. To further understand the viability of PEDv in the infected manure, we longitudinally monitored survivability and infectivity of PEDv in two open earthen manure storages (EMS; previously referred to as lagoon) from two different infected swine farms identified in the province of Manitoba, Canada. Our study revealed that PEDv could survive up to 9 months in the infected EMS after the initial outbreak in the farm. The viral load varied among different layers of the EMS with an average of 1.1 × 105 copies/ml of EMS, independent of EMS temperature and pH. In both studied EMS, the evidence of viral replication was observed through increased viral load in the later weeks of the samplings while there was no new influx of infected manure into the EMS, which was suggestive of presence of potential alternative hosts for PEDv within the EMS. Decreasing infectivity of virus over time irrespective of increased viral load suggested the possibility of PEDv evolution within the EMS and perhaps in the new host that negatively impacted virus infectivity. Viral load in the top layer of the EMS was low and mostly non-infective suggesting that environmental factors, such as UV and sunlight, could diminish the replicability and infectivity of the virus. Thus, frequent agitation of the EMS that could expose virus to UV and sunlight might be a potential strategy for reduction of PEDv load and infectivity in the infected EMS. PMID:27014197

  16. Resolving the viscoelasticity and anisotropy dependence of the mechanical properties of skin from a porcine model.

    PubMed

    Wong, W L E; Joyce, T J; Goh, K L

    2016-04-01

    The mechanical response of skin to external loads is influenced by anisotropy and viscoelasticity of the tissue, but the underlying mechanisms remain unclear. Here, we report a study of the main effects of tissue orientation (TO, which is linked to anisotropy) and strain rate (SR, a measure of viscoelasticity), as well as the interaction effects between the two factors, on the tensile properties of skin from a porcine model. Tensile testing to rupture of porcine skin tissue was conducted to evaluate the sensitivity of the tissue modulus of elasticity (E) and fracture-related properties, namely maximum stress [Formula: see text] and strain [Formula: see text] at [Formula: see text], to varying SR and TO. Specimens were excised from the abdominal skin in two orientations, namely parallel (P) and right angle (R) to the torso midline. Each TO was investigated at three SR levels, namely 0.007-0.015 [Formula: see text] (low), 0.040 [Formula: see text] (mid) and 0.065 [Formula: see text] (high). Two-factor analysis of variance revealed that the respective parameters responded differently to varying SR and TO. Significant changes in the [Formula: see text] were observed with different TOs but not with SR. The [Formula: see text] decreased significantly with increasing SR, but no significant variation was observed for different TOs. Significant changes in E were observed with different TOs; E increased significantly with increasing SR. More importantly, the respective mechanical parameters were not significantly influenced by interactions between SR and TO. These findings suggest that the trends associated with the changes in the skin mechanical properties may be attributed partly to differences in the anisotropy and viscoelasticity but not through any interaction between viscoelasticity and anisotropy. PMID:26156308

  17. Three dimensional electromechanical model of porcine heart with penetrating wound injury.

    PubMed

    Usyk, Taras; Kerckhoffs, Roy

    2005-01-01

    The aim of this study is development a prototype computational model of the pig heart that can be used to predict physiological responses to a penetrating wound injury. The pig has been chosen for this model studies because it shares many anatomical similarities with humans. Three-dimensional cubic Hermite finite element meshes based on detailed measurements of porcine anatomy combined into an integrated anatomic model. The pig ventricular model includes detailed left and right ventricular geometry and myofiber and laminar sheet orientations throughout the mesh. The cardiac mesh was refined and monodomain equations for action potential propagation solved using well-established collocation-Galerkin finite element methods. The membrane kinetic equations for the action potential model was based on detailed cellular models of transmembrane ionic fluxes and intracellular calcium fluxes in canine ventricular myocytes and human atrial myocytes. We modified the anisotropic myocardial conductivity tensor on the endocardial surface of the ventricles by making use of a surface model fitted to measured of Purkinje fiber network anatomy. The mechanical model compute regional three-dimensional stress and strain distributions using anisotropic constitutive laws referred to local material coordinate axes defined by local myofiber and laminar sheet orientations. Passive myocardial mechanics modeled using exponential orthotropic strain energy functions. Active systolic myocardial stresses computed from a multi-scale model that uses crossbridge theory to predict calcium-activated sarcomere length- and velocity-dependent tension filament tension. Since the electrical and mechanical models use a common finite element mesh as the parent parametric framework and both models are solved within our custom finite element package, it is straightforward to couple these models, as we have recently done for a model of coupled ventricular electromechanics. We apply the coupled electromechanical

  18. A comprehensive computational model of sound transmission through the porcine lung

    PubMed Central

    Dai, Zoujun; Peng, Ying; Henry, Brian M.; Mansy, Hansen A.; Sandler, Richard H.; Royston, Thomas J.

    2014-01-01

    A comprehensive computational simulation model of sound transmission through the porcine lung is introduced and experimentally evaluated. This “subject-specific” model utilizes parenchymal and major airway geometry derived from x-ray CT images. The lung parenchyma is modeled as a poroviscoelastic material using Biot theory. A finite element (FE) mesh of the lung that includes airway detail is created and used in comsol FE software to simulate the vibroacoustic response of the lung to sound input at the trachea. The FE simulation model is validated by comparing simulation results to experimental measurements using scanning laser Doppler vibrometry on the surface of an excised, preserved lung. The FE model can also be used to calculate and visualize vibroacoustic pressure and motion inside the lung and its airways caused by the acoustic input. The effect of diffuse lung fibrosis and of a local tumor on the lung acoustic response is simulated and visualized using the FE model. In the future, this type of visualization can be compared and matched with experimentally obtained elastographic images to better quantify regional lung material properties to noninvasively diagnose and stage disease and response to treatment. PMID:25190415

  19. A comprehensive computational model of sound transmission through the porcine lung.

    PubMed

    Dai, Zoujun; Peng, Ying; Henry, Brian M; Mansy, Hansen A; Sandler, Richard H; Royston, Thomas J

    2014-09-01

    A comprehensive computational simulation model of sound transmission through the porcine lung is introduced and experimentally evaluated. This "subject-specific" model utilizes parenchymal and major airway geometry derived from x-ray CT images. The lung parenchyma is modeled as a poroviscoelastic material using Biot theory. A finite element (FE) mesh of the lung that includes airway detail is created and used in comsol FE software to simulate the vibroacoustic response of the lung to sound input at the trachea. The FE simulation model is validated by comparing simulation results to experimental measurements using scanning laser Doppler vibrometry on the surface of an excised, preserved lung. The FE model can also be used to calculate and visualize vibroacoustic pressure and motion inside the lung and its airways caused by the acoustic input. The effect of diffuse lung fibrosis and of a local tumor on the lung acoustic response is simulated and visualized using the FE model. In the future, this type of visualization can be compared and matched with experimentally obtained elastographic images to better quantify regional lung material properties to noninvasively diagnose and stage disease and response to treatment. PMID:25190415

  20. Development and translational imaging of a TP53 porcine tumorigenesis model

    PubMed Central

    Sieren, Jessica C.; Meyerholz, David K.; Wang, Xiao-Jun; Davis, Bryan T.; Newell, John D.; Hammond, Emily; Rohret, Judy A.; Rohret, Frank A.; Struzynski, Jason T.; Goeken, J. Adam; Naumann, Paul W.; Leidinger, Mariah R.; Taghiyev, Agshin; Van Rheeden, Richard; Hagen, Jussara; Darbro, Benjamin W.; Quelle, Dawn E.; Rogers, Christopher S.

    2014-01-01

    Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs). TP53R167H/R167H mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous TP53 mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that TP53R167H/R167H pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers. PMID:25105366

  1. Endovascular Broad-Neck Aneurysm Creation in a Porcine Model Using a Vascular Plug

    SciTech Connect

    Muehlenbruch, Georg Nikoubashman, Omid; Steffen, Bjoern; Dadak, Mete; Palmowski, Moritz; Wiesmann, Martin

    2013-02-15

    Ruptured cerebral arterial aneurysms require prompt treatment by either surgical clipping or endovascular coiling. Training for these sophisticated endovascular procedures is essential and ideally performed in animals before their use in humans. Simulators and established animal models have shown drawbacks with respect to degree of reality, size of the animal model and aneurysm, or time and effort needed for aneurysm creation. We therefore aimed to establish a realistic and readily available aneurysm model. Five anticoagulated domestic pigs underwent endovascular intervention through right femoral access. A total of 12 broad-neck aneurysms were created in the carotid, subclavian, and renal arteries using the Amplatzer vascular plug. With dedicated vessel selection, cubic, tubular, and side-branch aneurysms could be created. Three of the 12 implanted occluders, two of them implanted over a side branch of the main vessel, did not induce complete vessel occlusion. However, all aneurysms remained free of intraluminal thrombus formation and were available for embolization training during a surveillance period of 6 h. Two aneurysms underwent successful exemplary treatment: one was stent-assisted, and one was performed with conventional endovascular coil embolization. The new porcine aneurysm model proved to be a straightforward approach that offers a wide range of training and scientific applications that might help further improve endovascular coil embolization therapy in patients with cerebral aneurysms.

  2. Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model

    PubMed Central

    2013-01-01

    Background Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis. N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro. NAC can affect several signaling pathways involving in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and inflammatory response. Therefore, NAC may not only protect against the direct injurious effects of oxidants, but also beneficially alter inflammatory events in colitis. This study was conducted to investigate whether NAC could alleviate the AA-induced colitis in a porcine model. Methods Weaned piglets were used to investigate the effects of NAC on AA-induced colitis. Severity of colitis was evaluated by colon histomorphology measurements, histopathology scores, tissue myeloperoxidase activity, as well as concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon. The protective role of NAC was assessed by measurements of antioxidant status, growth modulator, cell apoptosis, and tight junction proteins. Abundances of caspase-3 and claudin-1 proteins in colonic mucosae were determined by the Western blot method. Epidermal growth factor receptor, amphiregulin, tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4) mRNA levels in colonic mucosae were quantified using the real-time fluorescent quantitative PCR. Results Compared with the control group, AA treatment increased (P < 0.05) the histopathology scores, intraepithelial lymphocyte (IEL) numbers and density in the colon, myeloperoxidase activity, the concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon, while reducing (P < 0.05) goblet cell numbers and the protein/DNA ratio in the colonic mucosa. These adverse effects of AA were partially ameliorated (P < 0.05) by dietary

  3. Modeling the adaptive permeability response of porcine iliac arteries to acute changes in mural shear.

    PubMed

    Hazel, A L; Grzybowski, D M; Friedman, M H

    2003-04-01

    The hypothesis that much of the uptake of macromolecules by the vascular wall takes place while the endothelial lining is adapting to changes in its hemodynamic environment is being tested by a series of in vivo measurements of the uptake of Evans-blue-dye-labeled albumin by porcine iliac arteries subjected to acute changes in blood flow. The uptake data are interpreted through an ad hoc model of the dynamic permeability response that is proposed to accompany alterations in mural shear. The model is able to correlate, with a single set of parameters, the vascular response to a variety of experimental protocols, including sustained step increases and decreases in shear, and alternations in shear of various periods. The best-fit parameters of the model suggest that the adaptive response to an increase in shear proceeds with a latency of approximately 1.5 min and a time constant of approximately 90 min that is substantially shorter than the response to a decrease in shear. PMID:12723682

  4. A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration.

    PubMed

    Cullen, D Kacy; Harris, James P; Browne, Kevin D; Wolf, John A; Duda, John E; Meaney, David F; Margulies, Susan S; Smith, Douglas H

    2016-01-01

    Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive non-impact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI. PMID:27604725

  5. Intracoronary photodynamic therapy reduces neointimal growth without suppressing re‐endothelialisation in a porcine model

    PubMed Central

    Waksman, R; Leitch, I M; Roessler, J; Yazdi, H; Seabron, R; Tio, F; Scott, R W; Grove, R I; Rychnovsky, S; Robinson, B; Pakala, R; Cheneau, E

    2006-01-01

    Objective To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis. Methods 28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n  =  19) or the stented group (n  =  9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm2) was applied to activate the drug (n  =  10). Control arteries (n  =  9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis. Results Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by ⩽ 60% and 50% within BI and stented arteries (3.43 (0.27) mm2v 5.51 (0.52) mm2, p < 0.05; 4.0 (0.02) mm2v 6.0 (0.16) mm2, p < 0.01), respectively. Complete re‐endothelialisation was observed by immunohistochemical and gross histological analyses in all PDT and control arteries. There were no cases of aneurysm formation or thrombosis. Conclusion Intracoronary PhotoPoint PDT with MV0611 reduces intimal proliferation without suppressing re‐endothelialisation in a porcine model of restenosis. PMID:16399853

  6. Model based vibration monitoring

    SciTech Connect

    Esat, I.; Paya, B.; Badi, M.N.M.

    1996-11-01

    The principal source of vibratory excitation of gear system is the unsteady component of the relative angular motion of pair of meshing spur gears. This vibratory excitation is described by the transmission error. The transmission error present itself as a varying force at the contact point of the meshing gear teeth. The varying force is also influenced by the varying tooth stiffness due to change of orientation of teeth relative to each other, during the contact phase of each pair. Such a varying force produces both lateral and torsional excitation to the gear system. This paper presents analytical formulation of a simple two meshing spur gear system as a three mass system (18 DOF). The mathematical model also incorporates the analytical formulation of the tooth stiffness. The analytical results are compared with the experimental results. At this stage of analysis the procedure developed for handling the nonlinear influences of the tooth geometry is not fully implemented and the tooth stiffness taken as a constant value representing the average tooth stiffness. The comparison between the analytical and experimental results are encouraging as three main frequency obtained from FFT of the experimental results correlates very closely with the analytical results.

  7. Acellular hydrogel for regenerative burn wound healing: translation from a porcine model

    PubMed Central

    Papa, Arianne; Burke, Jacqueline; Volk, Susan W; Gerecht, Sharon

    2015-01-01

    Currently available skin grafts and skin substitute for healing following third-degree burn injuries is fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative fashion would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate vulnerary efficacy and accelerated healing mechanism of dextran-based hydrogel in third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved reepithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared to the dressing treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients. PMID:26358387

  8. Systemic Inflammatory Response After Natural Orifice Translumenal Surgery: Transvaginal Cholecystectomy in a Porcine Model

    PubMed Central

    Fan, Joe K. M.; Tong, Daniel K. H.; HO, David W. Y.; Luk, John; Law, Simon

    2009-01-01

    Objective: We analyzed circulating TNF-α and IL-6 to determine systemic inflammatory responses associated with transvaginal cholecystectomy in a porcine model. Methods: Six female pigs were used for a survival study after transvaginal cholecystectomy (NOTES group) using endoscopic submucosal dissection (ESD) instruments and a single-channel endoscope. Blood was drawn preoperatively and 24 hours and 48 hours postoperatively. Four pigs were used as controls. In addition, laparoscopic cholecystectomy was performed in 2 pigs for laparoscopic control. Results: In all 6 pigs in the NOTES group, no major intraoperative complications occurred. No significant differences were found between control, laparoscopic, and NOTES groups in terms of preoperative IL-6 level (P=0.897) and at 24 hours (P=0.790), and 48 hours postoperatively (P=0.945). Similarly, there was no significant difference in mean preoperative (P=0.349) and mean day 2 postoperative TNF-α levels (P=0.11). But a significant increase in day 1 postoperative TNF-α levels in the laparoscopic group compared with that in the control and NOTES groups was observed (P=0.049). One limitation of our study is that the sample size was relatively small. Conclusion: NOTES is safe in animal models in terms of anatomical and cellular level changes with minimal systemic inflammatory host responses elicited. Further study needs to be carried out in humans before NOTES can be recommended for routine use. PMID:19366533

  9. Finite element model of the temperature increase in excised porcine cadaver iris during direct illumination by femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Sun, Hui; Kurtz, Ronald M.; Juhasz, Tibor

    2012-07-01

    In order to model the thermal effect of laser exposure of the iris during laser corneal surgery, we simulated the temperature increase in porcine cadaver iris. The simulation data for the 60 kHz FS60 Laser showed that the temperature increased up to 1.23°C and 2.45°C (at laser pulse energy 1 and 2 µJ, respectively) by the 24 second procedure time. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using porcine cadaver iris. Simulation results of different types of femtosecond lasers indicate that the Laser in situ keratomileusis procedure does not present a safety hazard to the iris.

  10. A Triple Culture Model of the Blood-Brain Barrier Using Porcine Brain Endothelial cells, Astrocytes and Pericytes

    PubMed Central

    Thomsen, Louiza Bohn; Burkhart, Annette; Moos, Torben

    2015-01-01

    In vitro blood-brain barrier (BBB) models based on primary brain endothelial cells (BECs) cultured as monoculture or in co-culture with primary astrocytes and pericytes are useful for studying many properties of the BBB. The BECs retain their expression of tight junction proteins and efflux transporters leading to high trans-endothelial electric resistance (TEER) and low passive paracellular permeability. The BECs, astrocytes and pericytes are often isolated from small rodents. Larger species as cows and pigs however, reveal a higher yield, are readily available and have a closer resemblance to humans, which make them favorable high-throughput sources for cellular isolation. The aim of the present study has been to determine if the preferable combination of purely porcine cells isolated from the 6 months old domestic pigs, i.e. porcine brain endothelial cells (PBECs) in co-culture with porcine astrocytes and pericytes, would compare with PBECs co-cultured with astrocytes and pericytes isolated from newborn rats with respect to TEER value and low passive permeability. The astrocytes and pericytes were grown both as contact and non-contact co-cultures as well as in triple culture to examine their effects on the PBECs for barrier formation as revealed by TEER, passive permeability, and expression patterns of tight junction proteins, efflux transporters and the transferrin receptor. This syngenic porcine in vitro BBB model is comparable to triple cultures using PBECs, rat astrocytes and rat pericytes with respect to TEER formation, low passive permeability, and expression of hallmark proteins signifying the brain endothelium (tight junction proteins claudin 5 and occludin, the efflux transporters P-glycoprotein (PgP) and breast cancer related protein (BCRP), and the transferrin receptor). PMID:26241648

  11. Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model

    PubMed Central

    Shi, Haifeng; Li, Ruokun; Qiang, Jinwei; Li, Ying; Wang, Li; Sun, Rongxun

    2016-01-01

    Objective To evaluate multi-slice computed tomography (CT) perfusion imaging (CTPI) for identifying microcirculatory dysfunction in small intestinal ischemia−reperfusion (IR) injury in a porcine model. Materials and Methods Fifty-two pigs were randomly divided into 4 groups: (1) the IR group (n = 24), where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA) for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively); (2) the sham-operated (SO) group (n = 20), where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively); (3) the ischemia group (n = 4), where the SMA was separated and clamped for 2 h, without reperfusion, and (4) baseline group (n = 4), an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) and for histopathological examination. Results The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia). The blood flow (BF), blood volume (BV), and permeability surface (PS) among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion. Conclusion CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury. PMID:27458696

  12. A pilot study on ultrasound-assisted liposuction of the greater omentum in porcine models.

    PubMed

    Sumiyama, Kazuki; Utsunomiya, Kazunori; Ohya, Tomohiko; Aihara, Hiroyuki; Ikeda, Keiichi; Imazu, Hiroo; Tamai, Naoto; Nagano, Hiroshi; Ishinoda, Yasuhiro; Tajiri, Hisao

    2012-03-01

    The greater omentum is the largest depot of visceral fat, and recent studies implicate removal of omental fat as a therapeutic option for metabolic syndrome (MS). This study evaluated the technical feasibility of reducing omental fat by using ultrasound-assisted liposuction (UAL) in porcine models. We removed as much omental adipose tissues as possible with a novel ultrasonic aspirator specifically designed for visceral liposuction that was inserted into the peritoneal cavity via the bilateral hypochondrial trocars. The greater part of the omental surface was emulsified and suctioned within 12.4 ± 9.2 (mean ± SD) min. In the survival study, all animals survived for two weeks without clinically evident complications following UAL. Histological examinations confirmed a substantial reduction in omental fat in pigs subjected to UAL. In conclusion, the pilot animal study conducted here demonstrated the technical feasibility of omental liposuction. UAL thus has potential as a relatively non-invasive liposuction approach to treat MS by selectively reducing the visceral fat content of the greater omentum. PMID:21395461

  13. Development of Off-pump Mitral Valve Replacement in a Porcine Model

    PubMed Central

    Gillespie, Matthew J.; Aoki, Chikashi; Satoshi, Takebayashi; Shimaoka, Toru; McGarvey, Jeremy R.; Gorman, Robert C.; Gorman, Joseph H.

    2015-01-01

    Purpose We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV2) technology, which was developed to atraumatically anchor and seal in the mitral position. Description The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment whilst still maintaining the key principles necessary for atraumatic anchoring and sealing in the MV position. Evaluation Ten Yorkshire pigs underwent successful SMV2 device implantation via a left atriotomy (on-pump N=6; off-pump N=4). Echocardiography and angiography revealed excellent LV systolic function, no significant perivalvular leak, no MV stenosis, no left ventricular (LV) outflow tract obstruction and no aortic valve insufficiency. Necropsy demonstrated that the SMV2 devices were anchored securely. Conclusions This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model. PMID:25841820

  14. Anti-inflammatory effects of mannanase-hydrolyzed copra meal in a porcine model of colitis.

    PubMed

    Ibuki, Masahisa; Fukui, Kensuke; Kanatani, Hiroyuki; Mine, Yoshinori

    2014-05-01

    We evaluated the anti-inflammatory activity of mannanase-hydrolyzed copra meal (MNB), including β-1,4-mannobiose (67.8%), in a dextran sodium sulfate (DSS)-induced porcine model of intestinal inflammation. In the DSS-positive control (POS) and MNB treatment (MCM) groups, DSS was first administered to piglets via intragastric catheter for 5 days, followed by 5 days administration of saline or MCM. A negative control group (NEG) received a saline alternative to DSS and MNB. Inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability and neutrophil infiltration. Local production of TNF-α and IL-6 were analyzed by ELISA, colonic and ileal inflammatory gene expressions were assessed by real time RT-PCR, and CD4+CD25+ cell populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, D-mannitol gut permeation, colonic expression of the inflammatory mediators TNF-α and IL-6 and myeloperoxidase activity were significantly lower in the MCM group than in that of POS group. The mRNA levels of ileal IL-1β, IL-6, IL-17 and TNF-α were significantly lower following MCM treatment than with POS treatment.MNB exerts anti-inflammatory activity in vivo, suggesting that MNB is a novel therapeutic that may provide relief to human and animals suffering from intestinal inflammation. PMID:24430661

  15. Antibody Responses to Sarcoptes scabiei Apolipoprotein in a Porcine Model: Relevance to Immunodiagnosis of Recent Infection

    PubMed Central

    Rampton, Melanie; Walton, Shelley F.; Holt, Deborah C.; Pasay, Cielo; Kelly, Andrew; Currie, Bart J.; McCarthy, James S.; Mounsey, Kate E.

    2013-01-01

    No commercial immunodiagnostic tests for human scabies are currently available, and existing animal tests are not sufficiently sensitive. The recombinant Sarcoptes scabiei apolipoprotein antigen Sar s 14.3 is a promising immunodiagnostic, eliciting high levels of IgE and IgG in infected people. Limited data are available regarding the temporal development of antibodies to Sar s 14.3, an issue of relevance in terms of immunodiagnosis. We utilised a porcine model to prospectively compare specific antibody responses to a primary infestation by ELISA, to Sar s 14.3 and to S. scabiei whole mite antigen extract (WMA). Differences in the antibody profile between antigens were apparent, with Sar s 14.3 responses detected earlier, and declining significantly after peak infestation compared to WMA. Both antigens resulted in >90% diagnostic sensitivity from weeks 8–16 post infestation. These data provide important information on the temporal development of humoral immune responses in scabies and further supports the development of recombinant antigen based immunodiagnostic tests for recent scabies infestations. PMID:23762351

  16. Adipose tissue remodeling in a novel domestic porcine model of diet-induced obesity

    PubMed Central

    Pawar, Aditya S.; Zhu, Xiang-Yang; Eirin, Alfonso; Tang, Hui; Jordan, Kyra L.; Woollard, John R.; Lerman, Amir; Lerman, Lilach O.

    2014-01-01

    Objective To establish and characterize a novel domestic porcine model of obesity. Design and Methods Fourteen domestic pigs were fed normal (lean, n=7) or high-fat/high-fructose diet (obese, n=7) for 16 weeks. Subcutaneous abdominal adipose tissue biopsies were obtained after 8, 12 and 16 weeks of diet, and pericardial adipose tissue after 16 weeks, for assessments of adipocyte size, fibrosis, and inflammation. Adipose tissue volume and cardiac function were studied with multi-detector computed-tomography, and oxygenation with magnetic resonance imaging. Plasma lipids profiles, insulin resistance, and markers of inflammation were evaluated. Results Compared with lean, obese pigs had elevated cholesterol and triglycerides levels, blood pressure, and insulin resistance. Both abdominal and pericardial fat volume increased after 16 weeks of obese. In abdominal subcutaneous adipose tissue, adipocyte size and both tumor necrosis factor (TNF)-α expression progressively increased. Macrophage infiltration showed in both abdominal and pericardial adipose tissues. Circulating TNF-α increased in obese only at 16 weeks. Compared with Lean, obese pigs had similar global cardiac function, but myocardial perfusion and oxygenation were significantly impaired. Conclusion A high-fat/high-fructose diet induces in domestic pigs many characteristics of metabolic syndrome, which is useful to investigate the effects of the obesity. PMID:25627626

  17. Dynamic CT myocardial perfusion imaging: detection of ischemia in a porcine model with FFR verification

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    Dynamic cardiac CT perfusion (CTP) is a high resolution, non-invasive technique for assessing myocardial blood ow (MBF), which in concert with coronary CT angiography enable CT to provide a unique, comprehensive, fast analysis of both coronary anatomy and functional ow. We assessed perfusion in a porcine model with and without coronary occlusion. To induce occlusion, each animal underwent left anterior descending (LAD) stent implantation and angioplasty balloon insertion. Normal ow condition was obtained with balloon completely de ated. Partial occlusion was induced by balloon in ation against the stent with FFR used to assess the extent of occlusion. Prospective ECG-triggered partial scan images were acquired at end systole (45% R-R) using a multi-detector CT (MDCT) scanner. Images were reconstructed using FBP and a hybrid iterative reconstruction (iDose4, Philips Healthcare). Processing included: beam hardening (BH) correction, registration of image volumes using 3D cubic B-spline normalized mutual-information, and spatio-temporal bilateral ltering to reduce partial scan artifacts and noise variation. Absolute blood ow was calculated with a deconvolutionbased approach using singular value decomposition (SVD). Arterial input function was estimated from the left ventricle (LV) cavity. Regions of interest (ROIs) were identi ed in healthy and ischemic myocardium and compared in normal and occluded conditions. Under-perfusion was detected in the correct LAD territory and ow reduction agreed well with FFR measurements. Flow was reduced, on average, in LAD territories by 54%.

  18. Adenoviral gene transfer corrects the ion transport defect in the sinus epithelia of a porcine CF model.

    PubMed

    Potash, Andrea E; Wallen, Tanner J; Karp, Philip H; Ernst, Sarah; Moninger, Thomas O; Gansemer, Nicholas D; Stoltz, David A; Zabner, Joseph; Chang, Eugene H

    2013-05-01

    Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene (CFTR) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17-28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis. PMID:23511247

  19. Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead

    PubMed Central

    Weymann, Alexander; Patil, Nikhil Prakash; Sabashnikov, Anton; Jungebluth, Philipp; Korkmaz, Sevil; Li, Shiliang; Veres, Gabor; Soos, Pal; Ishtok, Roland; Chaimow, Nicole; Pätzold, Ines; Czerny, Natalie; Schies, Carsten; Schmack, Bastian; Popov, Aron-Frederik; Simon, André Rüdiger; Karck, Matthias; Szabo, Gabor

    2014-01-01

    Background A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Native hearts decellularized with preserved architecture and vasculature may provide an acellular tissue platform for organ regeneration. We sought to develop a tissue-engineered whole-heart neoscaffold in human-sized porcine hearts. Methods We decellularized porcine hearts (n = 10) by coronary perfusion with ionic detergents in a modified Langendorff circuit. We confirmed decellularization by histology, transmission electron microscopy and fluorescence microscopy, quantified residual DNA by spectrophotometry, and evaluated biomechanical stability with ex-vivo left-ventricular pressure/volume studies, all compared to controls. We then mounted the decellularized porcine hearts in a bioreactor and reseeded them with murine neonatal cardiac cells and human umbilical cord derived endothelial cells (HUVEC) under simulated physiological conditions. Results Decellularized hearts lacked intracellular components but retained specific collagen fibers, proteoglycan, elastin and mechanical integrity; quantitative DNA analysis demonstrated a significant reduction of DNA compared to controls (82.6±3.2 ng DNA/mg tissue vs. 473.2±13.4 ng DNA/mg tissue, p<0.05). Recellularized porcine whole-heart neoscaffolds demonstrated re-endothelialization of coronary vasculature and measurable intrinsic myocardial electrical activity at 10 days, with perfused organ culture maintained for up to 3 weeks. Conclusions Human-sized decellularized porcine hearts provide a promising tissue-engineering platform that may lead to future clinical strategies in the treatment of heart failure. PMID:25365554

  20. In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs.

    PubMed

    Wyns, H; Plessers, E; De Backer, P; Meyer, E; Croubels, S

    2015-08-15

    Lipopolysaccharide (LPS), a structural part of the outer membrane of Gram-negative bacteria, is one of the most effective stimulators of the immune system and has been widely applied in pigs as an experimental model for bacterial infection. For this purpose, a variety of Escherichia coli serotypes, LPS doses, routes and duration of administration have been used. LPS administration induces the acute phase response (APR) and is associated with dramatic hemodynamic, clinical and behavioral changes in pigs. Pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin (IL)-1 and IL-6 are involved in the induction of the eicosanoid pathway and the hepatic production of acute phase proteins, including C-reactive protein (CRP), haptoglobin (Hp) and pig major acute phase protein (pig-MAP). Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) play a major role in the development of fever and pulmonary hypertension in LPS-challenged pigs, respectively. The LPS-induced APR can be modulated by drugs. Steroidal and nonsteroidal anti-inflammatory drugs ((N)SAIDs) possess anti-inflammatory, antipyretic and analgesic properties through (non)-selective central and peripheral cyclooxygenase (COX) inhibition. Antimicrobial drugs, especially macrolide antibiotics, which are commonly used in veterinary medicine for the treatment of bacterial respiratory diseases, have been recurrently reported to exert clinically important immunomodulatory effects in human and murine research. To investigate the influence of these drugs on the clinical response, production of pro-inflammatory cytokines, acute phase proteins (APP) and the course of the febrile response in pigs, in vivo LPS inflammation models can be applied. Yet, to date, in vivo research on the immunomodulatory properties of antimicrobial drugs in these models in pigs is largely lacking. This review provides acritical overview of the use of in vivo porcine E. coli LPS inflammation models for the study of the APR, as

  1. Feasibility of 68Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome

    PubMed Central

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [15O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting 68Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([68Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [68Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [68Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [68Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion. PMID:27069763

  2. Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome.

    PubMed

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion. PMID:27069763

  3. Virtual Electrophysiologic Study in a Three-dimensional Cardiac MRI Model of Porcine Myocardial Infarction

    PubMed Central

    Ng, Jason; Jacobson, Jason T; Ng, Justin K; Gordon, David; Lee, Daniel C; Carr, James C.; Goldberger, Jeffrey J

    2012-01-01

    Objective This study sought to test the hypothesis that “virtual” electrophysiologic studies (EPS) on an anatomic platform generated by 3D MRI reconstruction of the left ventricle (LV) can reproduce the reentrant circuits of induced ventricular tachycardia (VT) in a porcine model of myocardial infarction (MI). Background Delayed-enhancement MRI has been used to characterize MI and “gray zones”, which are thought to reflect heterogeneous regions of viable and non-viable myocytes. Methods MI by coronary artery occlusion was induced in eight pigs. After a recovery period, 3D cardiac MRIs were obtained from each pig in-vivo. Normal areas, gray zones, and infarct cores were classified based on voxel intensity. In the computer model, gray zones were assigned slower conduction and longer action potential durations than those for normal myocardium. Virtual EPS was performed and was compared to results of actual in vivo programmed stimulation and non-contact mapping. Results The LV volumes ranged from 97.8 to 166.2 cm3 with 4.9 to 17.5% of voxels classified as infarct zones. Six of the seven pigs that developed VT during actual EPS were also inducible with virtual EPS. Four of the six pigs that had simulated VT had reentrant circuits that approximated the circuits seen with non-contact mapping, while the remaining two had similar circuits but propagating in opposite directions. Conclusions This initial study demonstrates the feasibility of applying a mathematical model to MRI reconstructions of the LV to predict VT circuits. Virtual EPS may be helpful to plan catheter ablation strategies or to identify patients who are at risk for future episodes of VT. PMID:22633654

  4. Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus PJ; Teuben, Michel PJ; Heeres, Marjolein; de Maat, Steven; de Jong, Renate; Maas, Coen; Kouwenberg, Lisanne HJA; Koenderman, Leo; van Solinge, Wouter W; de Jager, Saskia CA; Pasterkamp, Gerard; Hoefer, Imo E

    2015-01-01

    Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID:26282710

  5. Development of a Bronchial Wall Model: Triple Culture on a Decellularized Porcine Trachea.

    PubMed

    Melo, Esther; Kasper, Jennifer Y; Unger, Ronald E; Farré, Ramon; Kirkpatrick, Charles James

    2015-09-01

    In vitro coculture models mimicking the bronchial barrier are a significant step forward in investigating the behavior and function of the upper respiratory tract mucosa. To date, mostly synthetic materials have been used as substrates to culture the cells. However, decellularized tissues provide a more in vivo-like environment based on the native extracellular matrix. In this study, an in vitro, bronchial wall coculture model has been established using a decellularized, porcine luminal trachea membrane and employing three relevant human cell types. The tissue was decellularized and placed in plastic transwell supports. The human bronchial epithelial cell line, 16HBE14o-, was seeded on the apical side of the membrane with the human lung fibroblast cell line, Wi-38, and/or the microvascular endothelial cell line, ISO-HAS-1, seeded on the basolateral side. Transepithelial electrical resistance (TER) was measured over 10 days and tight/adherens junctions (ZO-1, occludin/β-catenin) were studied through immunofluorescence. Scanning electron microscopy (SEM) was performed to evaluate microvilli and cilia formation. All cultures grew successfully on the membrane. TER values of 555 Ω·cm(2) (±21, SEM) were achieved in the monoculture. Cocultures with fibroblasts reached 565 Ω·cm(2) (±41, SEM), with endothelial cells at 638 Ω·cm(2) (±37, SEM), and the triple culture achieved 552 Ω·cm(2) (±38, SEM). ZO-1, occludin, and β-catenin were expressed in 16HBE14o- under all culture conditions. Using SEM, a dense microvilli population was found. Prominent cell-cell contacts and clusters of emerging cilia could be identified. Fibroblasts and endothelial cells strengthened the formation of a tight barrier by the 16HBE14o-. Thus, the coculture of three relevant cell types in combination with native decellularized scaffolds as a substrate approaches more closely the in vivo situation and could be used to study mechanisms of upper respiratory damage and regeneration. PMID

  6. Cholesteryl esters accumulate in the heart in a porcine model of ischemia and reperfusion.

    PubMed

    Drevinge, Christina; Karlsson, Lars O; Ståhlman, Marcus; Larsson, Thomas; Perman Sundelin, Jeanna; Grip, Lars; Andersson, Linda; Borén, Jan; Levin, Malin C

    2013-01-01

    Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment. PMID:23637933

  7. Remote Ischemic Preconditioning Reduces Cerebral Oxidative Stress Following Hypothermic Circulatory Arrest in a Porcine Model.

    PubMed

    Arvola, Oiva; Haapanen, Henri; Herajärvi, Johanna; Anttila, Tuomas; Puistola, Ulla; Karihtala, Peeter; Tuominen, Hannu; Anttila, Vesa; Juvonen, Tatu

    2016-01-01

    Remote ischemic precondition has become prominent as one of the most promising methods to mitigate neurological damage following ischemic insult. The purpose of this study was to investigate whether the effects of remote ischemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes in a porcine model. A total of 12 female piglets were randomly assigned to 2 groups. The study group underwent an intervention of 4 cycles of 5-minute ischemic preconditioning on the right hind leg. All piglets underwent 60-minute hypothermic circulatory arrest. Oxidative stress marker 8-hydroxydeoxyguanosine (8-OHdG) was measured from blood samples with enzyme-linked immunosorbent assay. After 7 days of follow-up, samples from the brain, heart, kidney, and ovary were harvested for histopathologic examination. The immunohistochemical stainings of hypoxia marker hypoxia-inducible factor-1-α, oxidative stress marker 8-OHdG, DNA repair enzyme 8-oxoguanine glycosylase, and antioxidant response regulators nuclear factor erythroid 2-related factor 2 and protein deglycase were analyzed. The level of 8-OHdG referred to baseline was decreased in the sagittal sinus׳ blood samples in the study group after a prolonged deep hypothermic circulatory arrest at 360 minutes after reperfusion. Total histopathologic score was 3.8 (1.8-6.0) in the study group and was 4.4 (2.5-6.5) in the control group (P = 0.72), demonstrating no statistically significant difference in cerebral injury. Our findings demonstrate that the positive effects of remote ischemic preconditioning can be seen in cellular oxidative balance regulators in an animal model after 7 days of preconditioned ischemic insult. PMID:27568144

  8. Sclera-Choroid-RPE Transport of Eight β-Blockers in Human, Bovine, Porcine, Rabbit, and Rat Models

    PubMed Central

    Kadam, Rajendra S.; Cheruvu, Narayan P. S.; Edelhauser, Henry F.

    2011-01-01

    Purpose. To determine the influence of drug lipophilicity, ocular pigmentation, and species differences on transscleral solute transport. Methods. The transport of eight β-blockers across excised sclera/sclera-choroid-RPE (SCRPE) of albino rabbit, pigmented rabbit, human, porcine, and bovine eyes was determined over 6 hours. The ex vivo transscleral β-blocker transport to the vitreous at the end of 6 hours was determined in euthanatized, pigmented Brown Norway rats. The thicknesses of the sclera and SCRPE and the melanin content in choroid-RPE (CRPE) were measured to determine whether species differences in drug transport can be explained on this basis. Results. Solute lipophilicity inversely correlated with the SCRPE cumulative percentage of transport in all species (R2 ≥ 0.80). The CRPE impeded the SCRPE transport of all β-blockers (51%–64% resistance in the rabbits; 84%–99.8% in the bovine and porcine eyes) more than the sclera, with the impedance increasing with lipophilicity. SCRPE transport followed the trend albino rabbit > pigmented rabbit > human > porcine > bovine, and a cross-species comparison showed good Spearman's rho correlation (R2 ≥ 0.85). Bovine (R2 = 0.84), porcine (R2 = 0.84), and human (R2 = 0.71) SCRPE transport was more predictive than that in the rabbit models (R2 = 0.60–0.61) of transscleral solute transport to the vitreous in rats. The CRPE concentrations were higher in pigmented rabbits than in albino rabbits. The melanin content of the CRPE exhibited the trend albino rabbit ≪ pigmented rabbit < porcine ∼ bovine < rat. Normalization to scleral thickness abolished the species differences in scleral transport. Normalization to SCRPE thickness and melanin content significantly reduced species differences in SCRPE transport. Conclusions. Owing to the presence of pigment and drug binding, choroid-RPE is the principal barrier to transscleral β-blocker transport, with the barrier being more significant for lipophilic

  9. The rolling-circle melting-pot model for porcine circovirus DNA replication

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A stem-loop structure, formed by a pair of inverted repeats during DNA replication, is a conserved feature at the origin of DNA replication (Ori) among plant and animal viruses, bacteriophages and plasmids that replicate their genomes via the rolling-circle replication (RCR) mechanism. Porcine circo...

  10. Low-shear modelled microgravity environment maintains morphology and differentiated functionality of primary porcine hepatocyte cultures.

    PubMed

    Nelson, Leonard J; Walker, Simon W; Hayes, Peter C; Plevris, John N

    2010-01-01

    Hepatocytes cultured in conventional static culture rapidly lose polarity and differentiated function. This could be explained by gravity-induced sedimentation, which prevents formation of complete three-dimensional (3D) cell-cell/cell-matrix interactions and disrupts integrin-mediated signals (including the most abundant hepatic integrin alpha(5)beta(1)), important for cellular polarity and differentiation. Cell culture in a low fluid shear modelled microgravity (about 10(-2) g) environment promotes spatial colocation/self-aggregation of dissociated cells and induction of 3D differentiated liver morphology. Previously, we demonstrated the utility of a NASA rotary bioreactor in maintaining key metabolic functions and 3D aggregate formation of high-density primary porcine hepatocyte cultures over 21 days. Using serum-free chemically defined medium, without confounding interactions of exogenous bioscaffolding or bioenhancing surface materials, we investigated features of hepatic cellular polarity and differentiated functionality, including expression of hepatic integrin alpha(5), as markers of functional morphology. We report here that in the absence of exogenous biomatrix scaffolding, hepatocytes cultured in serum-free chemically defined medium in a microgravity environment rapidly (<24 h) form macroscopic (2-5 mm), compacted 3D hepatospheroid structures consisting of a shell of glycogen-positive viable cells circumscribing a core of eosinophilic cells. The spheroid shell layers exhibited ultrastructural, morphological and functional features of differentiated, polarized hepatic tissue including strong expression of the integrin alpha(5) subunit, functional bile canaliculi, albumin synthesis, and fine ultrastructure reminiscent of in vivo hepatic tissue. The low fluid shear microgravity environment may promote tissue-like self-organization of dissociated cells, and offer advantages over spheroids cultured in conventional formats to delineate optimal conditions for

  11. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    SciTech Connect

    Choi, Jae Woong Lu, David S. K. Osuagwu, Ferdnand Raman, Steven; Lassman, Charles

    2013-11-07

    PurposeTo evaluate the chronological effects of irreversible electroporation (IRE) on large hilar bile ducts in an in vivo porcine model correlated with computed tomography (CT) cholangiography and histopathology.Materials and MethodsTwelve IRE zones were made along hilar bile ducts intraoperatively under ultrasound (US)-guidance in 11 pigs. Paired electrodes were placed either on opposing sides of the bile duct (straddle [STR]) or both on one side of the bile duct (one-sided [OSD]). The shortest electrode-to-duct distance was classified as periductal (≤2 mm) or nonperiductal (>2 mm). CT cholangiography and laboratory tests were performed before IRE and again at 2 days, 4 weeks, and 8 weeks after IRE. Degree of bile duct injury were graded as follows: grade 0 = no narrowing; grade 1 = ≤50 % duct narrowing; grade 2 = >50 % narrowing without proximal duct dilatation; grade 3 = grade 2 with proximal duct dilatation; and grade 4 = grade 3 with enzyme elevation. Pigs were selected for killing and histopathology at 2 days, 4, and 8 weeks.ResultsNonperiductal electrode placement produced no long-term strictures in 5 of 5 ducts. Periductal electrode placement produced mild narrowing in 6 of 7 ducts: 5 grade 1 and 1 grade 2. None showed increased enzymes. There was no significant difference between STR versus OSD electrode placement. Histopathology showed minor but relatively greater ductal mural changes in narrowed ducts.ConclusionIn the larger hilar ducts, long-term patency and mural integrity appear resistant to IRE damage with the energy deposition used, especially if the electrode is not immediately periductal in position.

  12. Carbon dioxide laser ablation with immediate autografting in a full-thickness porcine burn model.

    PubMed Central

    Glatter, R D; Goldberg, J S; Schomacker, K T; Compton, C C; Flotte, T J; Bua, D P; Greaves, K W; Nishioka, N S; Sheridan, R L

    1998-01-01

    OBJECTIVE: To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply débrided wounds in a porcine model. SUMMARY BACKGROUND DATA: Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. METHODS: Full-thickness paravertebral burn wounds measuring 36 cm2 were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 microm of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. RESULTS: The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18+/-0.05 mm. The mean graft take was 96+/-11% in manual sites and 93+/-8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. CONCLUSIONS: Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome. Images Figure 1. Figure 2. Figure 3

  13. Laparoendoscopic single-site simple nephrectomy using a magnetic anchoring system in a porcine model

    PubMed Central

    Choi, Young Hyo; Lee, Hye Won; Lee, Seo Yeon; Han, Deok Hyun; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong

    2016-01-01

    Purpose Magnetic anchoring devices may reduce the number of port sites needed in laparoscopic surgery. In this study, we prospectively assessed the feasibility of using a magnetic anchoring and guidance system (MAGS) in laparoendoscopic single-site (LESS) surgery performed by novices. Materials and Methods A total of 10 LESS simple nephrectomies were performed with or without MAGS in a nonsurvival porcine model by 6 operators with no previous LESS surgery experience. After installation of the homemade single port, an intra-abdominal magnet was fixed to the renal parenchyma with suturing and stabilized by an external magnet placed on the flank so that the position of the kidney could be easily changed by moving the external handheld magnet. The length of the procedure and any intraoperative complications were evaluated. Results Operative time (mean±standard deviation) was shorter in the group using the magnetic anchoring device (M-LESS-N) than in the group with conventional LESS nephrectomy (C-LESS-N) (63±20.8 minutes vs. 82±40.7 minutes, respectively). Although all nephrectomies were completed uneventfully in the M-LESS-N group, renal vein injury occurred during dissection of the renal hilum in two cases of C-LESS-N and was resolved by simultaneous transection of the renal artery and vein with an Endo-GIA stapler. Conclusions LESS-N using MAGS is a feasible technique for surgeons with no LESS surgery experience. Taking into account the 2 cases of renal vein injury in the C-LESS-N group, the application of MAGS may be beneficial for overcoming the learning curve of LESS surgery. PMID:27195320

  14. Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model.

    PubMed

    Parker-Cote, Jennifer L; O'Rourke, Dorcas P; Brewer, Kori L; Lertpiriyapong, Kvin; Punja, Mohan; Bush, Sean P; Miller, Susan N; Meggs, William J

    2015-12-01

    Antivenom is the definitive treatment for venomous snakebites. Alternative treatments warrant investigation because antivenom is sometimes unavailable, expensive, and can have deleterious side effects. This study assesses the efficacy of trypsin to treat coral snake envenomation in an in vivo porcine model. A randomized, blinded study was conducted. Subjects were 13 pigs injected subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right distal hind limb. After 1 min, subjects were randomized to have the envenomation site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a blinded investigator. Clinical endpoint was survival for 72 h or respiratory depression defined as respiratory rate <15 breaths per minute, falling pulse oximetry, or agonal respirations. Fisher's exact t test was used for between group comparisons. Average time to toxicity for the saline control was 263 min (191-305 min). The development of respiratory depression occurred more frequently in control pigs than treated pigs (p = 0.009). Four of the six pigs that received trypsin survived to the end of the 3-day study. No control pigs survived. Two of the trypsin treatment pigs died with times to toxicity of 718 and 971 min. Survival to 12 and 24 h was significantly greater in the trypsin treatment group (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic enzyme, at the site of envenomation decreased the toxicity of eastern coral snake venom and increased survival significantly. Further investigation is required before these results can be extended to human snakebites. PMID:25952763

  15. Donor site healing dynamics: molecular, histological, and noninvasive imaging assessment in a porcine model.

    PubMed

    Mauskar, Neil A; Sood, Subeena; Travis, Taryn E; Matt, Sarah E; Mino, Matthew J; Burnett, Mary-Susan; Moffatt, Lauren T; Fidler, Philip; Epstein, Stephen E; Jordan, Marion H; Shupp, Jeffrey W

    2013-01-01

    Understanding the physiology of donor site healing will lead to advances in how these wounds are treated and may ultimately allow faster healing, more frequent autografting, and more effective care of the burn-injured patient. Unfortunately, a paucity of data exists regarding perfusion metrics over the course of donor site healing. Furthermore, there are no studies that interrelate indices of perfusion with the molecular and cellular processes of donor site healing. Male Duroc pigs were anesthetized and donor site wounds were created using a Zimmer dermatome at a depth of 0.060 inch (1.52 mm). Digital photographs, laser Doppler images, and punch biopsies were obtained before and after excision and on days 2, 4, 7, 9, 11, 14, and 16 until wounds were healed. RNA isolation was performed and quantitative polymerase chain reaction was used to examine differential gene expression over the time course. Formalin-fixed biopsies were embedded in paraffin, sectioned, stained, and examined. Wound surfaces were 83% re-epithelialized by day 16. Perfusion peaked on day 2 then declined, but it remained significantly elevated compared to before excision (P < .05). From day 9 onward, mean perfusion units were not significantly different from baseline (P < .05). Twenty-two representative genes were selected for examination. RNA expression of collagen, tenascin-cytoactin, inflammatory cytokines, remodeling enzymes, growth factors, and Wnt was increased. Inflammatory cells and cytokines were demonstrated histologically. Nuclei per high powered field peaked at day 7 and neodermal thickness increased daily to day 14. A novel porcine model for donor site wound healing that interrelates re-epithelilaizationand perfusion with molecular and cellular indices has been demonstrated. PMID:23511287

  16. Experimental laparoscopic and thoracoscopic discectomy and instrumented spinal fusion. A feasibility study using a porcine model.

    PubMed

    Mühlbauer, M; Ferguson, J; Losert, U; Koos, W T

    1998-03-01

    To explore the safety and the effectiveness of laparoscopic and thoracoscopic spinal surgery, an acute/non-survival animal trial was performed in 5 pigs using rigid and flexible endoscopes, flouroscopy, a holmium-YAG laser, and prototype instruments and implants. Our study aimed to approach the intervertebral disc space and spinal canal using laparoscopic and thoracoscopic techniques and to explore the potential and limits for endoscopic anterior spinal decompression and fusion. In a lateral recumbency access was provided to the anterolateral aspect of the lumbar spine from L1/2 to L7/S1, the thoracic spine was accessible from T2/3 to the diaphragmatic insertion. Complete disc space emptying with penetration into the spinal canal could be performed, epidural bleeding could be controlled by a hemostatic sponge, however bleeding restricted visualization for further endoscopic manipulation in the spinal canal. Intervertebral fusion was accomplished at T6/7, L4/5 and L7/S1 using small fragment plates with 3.5 mm screws and iliac bone grafts or prototype carbon fiber cages. On post mortem examination we found no dural tears and no nerve root damage, all animals had stabilized fusion sites and good implant position. We conclude that minimally invasive thoracoscopic and laparoscopic approaches to the spine are feasible and safe to perform disc decompression and implant placement for spinal fusion. In addition to currently performed laparoscopic interbody fusion, also plate fixation to reestablish lordosis of the lumbar spine is feasible at least in the porcine model. Careful disc decompression must be performed prior to implant introduction to prevent iatrogenic disc protrusion and spinal cord or nerve root compression. However, further surgical exploration of the spinal canal using these techniques does not provide adequate visualization of epidural spaces and therefore must be regarded as unsafe. PMID:9565956

  17. PET Imaging of Serotonin Transporters With 4-[(18)F]-ADAM in a Parkinsonian Rat Model With Porcine Neural Xenografts.

    PubMed

    Chiu, Chuang-Hsin; Li, I-Hsun; Weng, Shao-Ju; Huang, Yuahn-Sieh; Wu, Shinn-Chih; Chou, Ta-Kai; Huang, Wen-Sheng; Liao, Mei-Hsiu; Shiue, Chyng-Yann; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the nigrostriatal pathway. Apart from effective strategies to halt the underlying neuronal degeneration, cell replacement now offers novel prospects for PD therapy. Porcine embryonic neural tissue has been considered an alternative source to human fetal grafts in neurodegenerative disorders because its use avoids major practical and ethical issues. This study was undertaken to evaluate the effects of embryonic day 27 (E27) porcine mesencephalic tissue transplantation in a PD rat model using animal positron emission tomography (PET) coupled with 4-[(18)F]-ADAM, a serotonin transporter (SERT) imaging agent. The parkinsonian rat was induced by injecting 6-hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal pathway. The apomorphine-induced rotation behavioral test and 4-[(18)F]-ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the second week following 6-OHDA lesioning, the parkinsonian rat rotates substantially on apomorphine-induced contralateral turning. In addition, the mean striatal-specific uptake ratio (SUR) of 4-[(18)F]-ADAM decreased by 44%. After transplantation, the number of drug-induced rotations decreased markedly, and the mean SUR of 4-[(18)F]-ADAM and the level of SERT immunoreactivity (SERT-ir) in striatum were partially restored. The mean SUR level was restored to 71% compared to that for the contralateral intact side, which together with the abundant survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery at the fourth week postgraft. In regard to the extent of donor-derived cells, we found the neurons of the xenografts from E27 transgenic pigs harboring red fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted area. Thus, transplanted E27 porcine mesencephalic tissue may restore dopaminergic and serotonergic systems in the parkinsonian rat

  18. Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model

    PubMed Central

    Sutton, Jonathan T.; Ivancevich, Nikolas M.; Perrin, Stephen R.; Vela, Deborah C.; Holland, Christy K.

    2013-01-01

    Using an FDA-approved contrast agent (Definity®) and thrombolytic drug (rt-PA), we investigated ultrasound-enhanced thrombolysis in two whole-blood clot models. Porcine venous blood was collected from donor hogs and coagulated in two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombolysis model, while an intermittent ultrasound scheme previously developed to maximize stable cavitation was applied and acoustic emissions were detected. Exposure of clots to 3.15 μg/mL rt-PA promoted lysis in both clot models, compared to exposure to plasma alone. However, in the presence of rt-PA, Definity®, and ultrasound, only unretracted clots experienced significant enhancement of thrombolysis compared to treatment with rt-PA. In these clots, microscopy studies revealed loose erythrocyte aggregates, a significantly less extensive fibrin network, and a higher porosity, which may facilitate increase penetration of thrombolytics by cavitation. PMID:23453629

  19. First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 5: recipient monitoring and response plan for preventing disease transmission.

    PubMed

    Denner, Joachim; Tönjes, Ralf R; Takeuchi, Yasu; Fishman, Jay; Scobie, Linda

    2016-01-01

    Xenotransplantation of porcine cells, tissues, and organs may be associated with the transmission of porcine microorganisms to the human recipient. A previous, 2009, version of this consensus statement focused on strategies to prevent transmission of porcine endogenous retroviruses (PERVs). This version addresses potential transmission of all porcine microorganisms including monitoring of the recipient and provides suggested approaches to the monitoring and prevention of disease transmission. Prior analyses assumed that most microorganisms other than the endogenous retroviruses could be eliminated from donor animals under appropriate conditions which have been called "designated pathogen-free" (DPF) source animal production. PERVs integrated as proviruses in the genome of all pigs cannot be eliminated in that manner and represent a unique risk. Certain microorganisms are by nature difficult to eliminate even under DPF conditions; any such clinically relevant microorganisms should be included in pig screening programs. With the use of porcine islets in clinical trials, special consideration has to be given to the presence of microorganisms in the isolated islet tissue to be used and also to the potential use of encapsulation. It is proposed that microorganisms absent in the donor animals by sensitive microbiological examination do not need to be monitored in the transplant recipient; this will reduce costs and screening requirements. Valid detection assays for donor and manufacturing-derived microorganisms must be established. Special consideration is needed to preempt potential unknown pathogens which may pose a risk to the recipient. This statement summarizes the main achievements in the field since 2009 and focus on issues and solutions with microorganisms other than PERV. PMID:26918415

  20. Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model

    PubMed Central

    Kim, Sook Young; Cho, Young In; Lee, Kwang Suk; Kim, Kwang Hyun; Yang, Seung Choul; Han, Woong Kyu

    2015-01-01

    Ischemic preconditioning (IPC) is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI). Currently, IPC’s mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control), remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe), and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl). Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC. PMID:26489007

  1. Geophysical Model Applications for Monitoring

    SciTech Connect

    Pasyanos, M; Walter, W; Tkalcic, H; Franz, G; Gok, R; Rodgers, A

    2005-07-11

    Geophysical models constitute an important component of calibration for nuclear explosion monitoring. We will focus on four major topics and their applications: (1) surface wave models, (2) receiver function profiles, (3) regional tomography models, and (4) stochastic geophysical models. First, we continue to improve upon our surface wave model by adding more paths. This has allowed us to expand the region to all of Eurasia and into Africa, increase the resolution of our model, and extend results to even shorter periods (7 sec). High-resolution models exist for the Middle East and the YSKP region. The surface wave results can be inverted either alone, or in conjunction with other data, to derive models of the crust and upper mantle structure. One application of the group velocities is to construct phase-matched filters in combination with regional surface-wave magnitude formulas to improve the mb:Ms discriminant and extend it to smaller magnitude events. Next, we are using receiver functions, in joint inversions with the surface waves, to produce profiles directly under seismic stations throughout the region. In the past year, we have been focusing on deployments throughout the Middle East, including the Arabian Peninsula and Turkey. By assembling the results from many stations, we can see how regional seismic phases are affected by complicated upper mantle structure, including lithospheric thickness and anisotropy. The next geophysical model item, regional tomography models, can be used to predict regional travel times such as Pn and Sn. The times derived by the models can be used as a background model for empirical measurements or, where these don't exist, simply used as is. Finally, we have been exploring methodologies such as Markov Chain Monte Carlo (MCMC) to generate data-driven stochastic models. We have applied this technique to the YSKP region using surface wave dispersion data, body wave travel time data, receiver functions, and gravity data. The models

  2. Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model

    PubMed Central

    Hacker, Stefan; Mittermayr, Rainer; Nickl, Stefanie; Haider, Thomas; Lebherz-Eichinger, Diana; Beer, Lucian; Mitterbauer, Andreas; Leiss, Harald; Zimmermann, Matthias; Schweiger, Thomas; Keibl, Claudia; Hofbauer, Helmut; Gabriel, Christian; Pavone-Gyöngyösi, Mariann; Redl, Heinz; Tschachler, Erwin; Mildner, Michael; Ankersmit, Hendrik Jan

    2016-01-01

    Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs. Necrotic areas were excised and the wounds were covered with split-thickness mesh skin grafts. Wounds were treated repeatedly with either the secretome of cultured PBMCs (SecPBMC), apoptotic PBMCs (Apo-SecPBMC), or controls. The wounds treated with Apo-SecPBMC had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-SecPBMC had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-SecPBMC significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting. PMID:27125302

  3. Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model.

    PubMed

    Hacker, Stefan; Mittermayr, Rainer; Nickl, Stefanie; Haider, Thomas; Lebherz-Eichinger, Diana; Beer, Lucian; Mitterbauer, Andreas; Leiss, Harald; Zimmermann, Matthias; Schweiger, Thomas; Keibl, Claudia; Hofbauer, Helmut; Gabriel, Christian; Pavone-Gyöngyösi, Mariann; Redl, Heinz; Tschachler, Erwin; Mildner, Michael; Ankersmit, Hendrik Jan

    2016-01-01

    Burn wounds pose a serious threat to patients and often require surgical treatment. Skin grafting aims to achieve wound closure but requires a well-vascularized wound bed. The secretome of peripheral blood mononuclear cells (PBMCs) has been shown to improve wound healing and angiogenesis. We hypothesized that topical application of the PBMC secretome would improve the quality of regenerating skin, increase angiogenesis, and reduce scar formation after burn injury and skin grafting in a porcine model. Full-thickness burn injuries were created on the back of female pigs. Necrotic areas were excised and the wounds were covered with split-thickness mesh skin grafts. Wounds were treated repeatedly with either the secretome of cultured PBMCs (Sec(PBMC)), apoptotic PBMCs (Apo-Sec(PBMC)), or controls. The wounds treated with Apo-Sec(PBMC) had an increased epidermal thickness, higher number of rete ridges, and more advanced epidermal differentiation than controls. The samples treated with Apo-Sec(PBMC) had a two-fold increase in CD31+ cells, indicating more angiogenesis. These data suggest that the repeated application of Apo-Sec(PBMC) significantly improves epidermal thickness, angiogenesis, and skin quality in a porcine model of burn injury and skin grafting. PMID:27125302

  4. Ultrasound Evaluation of the Combined Effects of Thoracolumbar Fascia Injury and Movement Restriction in a Porcine Model

    PubMed Central

    Bishop, James H.; Fox, James R.; Maple, Rhonda; Loretan, Caitlin; Badger, Gary J.; Henry, Sharon M.; Vizzard, Margaret A.; Langevin, Helene M.

    2016-01-01

    The persistence of back pain following acute back “sprains” is a serious public health problem with poorly understood pathophysiology. The recent finding that human subjects with chronic low back pain (LBP) have increased thickness and decreased mobility of the thoracolumbar fascia measured with ultrasound suggest that the fasciae of the back may be involved in LBP pathophysiology. This study used a porcine model to test the hypothesis that similar ultrasound findings can be produced experimentally in a porcine model by combining a local injury of fascia with movement restriction using a “hobble” device linking one foot to a chest harness for 8 weeks. Ultrasound measurements of thoracolumbar fascia thickness and shear plane mobility (shear strain) during passive hip flexion were made at the 8 week time point on the non-intervention side (injury and/or hobble). Injury alone caused both an increase in fascia thickness (p = .007) and a decrease in fascia shear strain on the non-injured side (p = .027). Movement restriction alone did not change fascia thickness but did decrease shear strain on the non-hobble side (p = .024). The combination of injury plus movement restriction had additive effects on reducing fascia mobility with a 52% reduction in shear strain compared with controls and a 28% reduction compared to movement restriction alone. These results suggest that a back injury involving fascia, even when healed, can affect the relative mobility of fascia layers away from the injured area, especially when movement is also restricted. PMID:26820883

  5. Evaluation of a minimally invasive renal cooling device using heat transfer analysis and an in vivo porcine model.

    PubMed

    Cervantes, Thomas M; Summers, Edward K; Batzer, Rachel; Simpson, Christie; Lewis, Raymond; Dhanani, Nadeem N; Slocum, Alexander H

    2013-06-01

    Partial nephrectomy is the gold standard treatment for renal cell carcinoma. This procedure requires temporary occlusion of the renal artery, which can cause irreversible damage due to warm ischemia after 30 min. Open surgical procedures use crushed ice to induce a mild hypothermia of 20°C in the kidney, which can increase allowable ischemia time up to 2.5 h. The Kidney Cooler device was developed previously by the authors to achieve renal cooling using a minimally invasive approach. In the present study an analytical model of kidney cooling in situ was developed using heat transfer equations to determine the effect of kidney thickness on cooling time. In vivo porcine testing was conducted to evaluate the cooling performance of this device and to identify opportunities for improved surgical handling. Renal temperature was measured continuously at 6 points using probes placed orthogonally to each other within the kidney. Results showed that the device can cool the core of the kidney to 20°C in 10-20 min. Design enhancements were made based on surgeon feedback; it was determined that the addition of an insulating air layer below the device increased difficulty of positioning the device around the kidney and did not significantly enhance cooling performance. The Kidney Cooler has been shown to effectively induce mild renal hypothermia of 20°C in an in vivo porcine model. PMID:22951039

  6. Simultaneous irrigation and negative pressure wound therapy enhances wound healing and reduces wound bioburden in a porcine model.

    PubMed

    Davis, Kathryn; Bills, Jessica; Barker, Jenny; Kim, Paul; Lavery, Lawrence

    2013-01-01

    Infected foot wounds are one of the most common reasons for hospitalization and amputation among persons with diabetes. The objective of the study was to investigate a new wound therapy system that employs negative pressure wound therapy (NPWT) with simultaneous irrigation therapy. For this study, we used a porcine model with full-thickness excisional wounds, inoculated with Pseudomonas aeruginosa. Wounds were treated for 21 days of therapy with either NPWT, NPWT with simultaneous irrigation therapy using normal saline or polyhexanide biguanide (PHMB) at low or high flow rates, or control. Data show that NPWT with either irrigation condition improved wound healing rates over control-treated wounds, yet did not differ from NPWT alone. NPWT improved bioburden over control-treated wounds. NPWT with simultaneous irrigation further reduced bioburden over control and NPWT-treated wounds; however, flow rate did not affect these outcomes. Together, these data show that NPWT with simultaneous irrigation therapy with either normal saline or PHMB has a positive effect on bioburden in a porcine model, which may translate clinically to improved wound healing outcomes. PMID:24134060

  7. The intrapleural volume threshold for ultrasound detection of pneumothoraces: An experimental study on porcine models

    PubMed Central

    2013-01-01

    Background Small pneumothoraxes (PTXs) may not impart an immediate threat to trauma patients after chest injuries. However, the amount of pleural air may increase and become a concern for patients who require positive pressure ventilation or air ambulance transport. Lung ultrasonography (US) is a reliable tool in finding intrapleural air, but the performance characteristics regarding the detection of small PTXs need to be defined. The study aimed to define the volume threshold of intrapleural air when PTXs are accurately diagnosed with US and compare this volume with that for chest x-ray (CXR). Methods Air was insufflated into a unilateral pleural catheter in seven incremental steps (10, 25, 50, 100, 200, 350 and 500 mL) in 20 intubated porcine models, followed by a diagnostic evaluation with US and a supine anteroposterior CXR. The sonographers continued the US scanning until the PTXs could be ruled in, based on the pathognomonic US “lung point” sign. The corresponding threshold volume was noted. A senior radiologist interpreted the CXR images. Results The mean threshold volume to confirm the diagnosis of PTX using US was 18 mL (standard deviation of 13 mL). Sixty-five percent of the PTXs were already diagnosed at 10 mL of intrapleural air; 25%, at 25 mL; and the last 10%, at 50 mL. At an air volume of 50 mL, the radiologist only identified four out of 20 PTXs in the CXR pictures; i.e., a sensitivity of 20% (95% CI: 7%, 44%). The sensitivity of CXR increased as a function of volume but leveled off at 67%, leaving one-third (1/3) of the PTXs unidentified after 500 mL of insufflated air. Conclusion Lung US is very accurate in diagnosing even small amounts of intrapleural air and should be performed by clinicians treating chest trauma patients when PTX is among the differential diagnoses. PMID:23453044

  8. Scabies Mites Alter the Skin Microbiome and Promote Growth of Opportunistic Pathogens in a Porcine Model

    PubMed Central

    Swe, Pearl M.; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja

    2014-01-01

    Background The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. Methodology/Principal Findings In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. Conclusions/Significance This is the first

  9. Establishment of a simplified in vitro porcine blood–brain barrier model with high transendothelial electrical resistance

    PubMed Central

    Patabendige, Adjanie; Skinner, Robert A.; Abbott, N. Joan

    2013-01-01

    Good in vitro blood–brain barrier (BBB) models that mimic the in vivo BBB phenotype are essential for studies on BBB functionality and for initial screening in drug discovery programmes, as many potential therapeutic drug candidates have poor BBB permeation. Difficulties associated with the availability of human brain tissue, coupled with the time and cost associated with using animals for this kind of research have led to the development of non-human cell culture models. However, most BBB models display a low transendothelial electrical resistance (TEER), which is a measure of the tightness of the BBB. To address these issues we have established and optimised a robust, simple to use in vitro BBB model using porcine brain endothelial cells (PBECs). The PBEC model gives high TEER without the need for co-culture with astrocytes (up to 1300 Ω cm2 with a mean TEER of ∼800 Ω cm2) with well organised tight junctions as shown by immunostaining for occludin and claudin-5. Functional assays confirmed the presence of high levels of alkaline phosphatase (ALP), and presence of the efflux transporter, P-glycoprotein (P-gp, ABCB1). Presence of the breast cancer resistance protein (BCRP, ABCG2) was confirmed by TaqMan real-time RT-PCR assay. Real-time RT-PCR assays for BCRP, occludin and claudin-5 demonstrated no significant differences between batches of PBECs, and also between primary and passage 1 PBECs. A permeability screen of 10 compounds demonstrated the usefulness of the model as a tool for drug permeability studies. Qualitative and quantitative results from this study confirm that this in vitro porcine BBB model is reliable and robust; it is also simpler to generate than most other BBB models. This article is part of a Special Issue entitled Electrical Synapses. PMID:22789905

  10. Vesicoureteral reflux in young children: a study of radiometric thermometry as detection modality using an ex vivo porcine model.

    PubMed

    Jacobsen, Svein; Klemetsen, Øystein; Birkelund, Yngve

    2012-09-01

    Microwave radiometry is evaluated for renal thermometry tailored to detect the pediatric condition of vesicoureteral urine reflux (VUR) from the bladder through the ureter into the kidney. Prior to a potential reflux event, the urine is heated within the bladder by an external body contacting a hyperthermia applicator to generate a fluidic contrast temperature relative to normal body temperature. A single band, miniaturized radiometer (operating at 3.5 GHz) is connected to an electromagnetic-interference-shielded and suction-coupled elliptical antenna to receive thermal radiation from an ex vivo porcine phantom model. Brightness (radiometric) and fiberoptic temperature data are recorded for varying urine phantom reflux volumes (20-40 mL) and contrast temperatures ranging from 2 to 10 °C within the kidney phantom. The kidney phantom itself is located at 40 mm depth (skin-to-kidney center distance) and surrounded by the porcine phantom. Radiometric step responses to injection of urine simulant by a syringe are shown to be highly correlated with in situ kidney temperatures measured by fiberoptic probes. Statistically, the performance of the VUR detecting scheme is evaluated by error probabilities of making a wrong decision. Laboratory testing of the radiometric system supports the feasibility of passive non-invasive kidney thermometry for the detection of VUR classified within the two highest grades. PMID:22892477

  11. Vesicoureteral reflux in young children: a study of radiometric thermometry as detection modality using an ex vivo porcine model

    NASA Astrophysics Data System (ADS)

    Jacobsen, Svein; Klemetsen, Øystein; Birkelund, Yngve

    2012-09-01

    Microwave radiometry is evaluated for renal thermometry tailored to detect the pediatric condition of vesicoureteral urine reflux (VUR) from the bladder through the ureter into the kidney. Prior to a potential reflux event, the urine is heated within the bladder by an external body contacting a hyperthermia applicator to generate a fluidic contrast temperature relative to normal body temperature. A single band, miniaturized radiometer (operating at 3.5 GHz) is connected to an electromagnetic-interference-shielded and suction-coupled elliptical antenna to receive thermal radiation from an ex vivo porcine phantom model. Brightness (radiometric) and fiberoptic temperature data are recorded for varying urine phantom reflux volumes (20-40 mL) and contrast temperatures ranging from 2 to 10 °C within the kidney phantom. The kidney phantom itself is located at 40 mm depth (skin-to-kidney center distance) and surrounded by the porcine phantom. Radiometric step responses to injection of urine simulant by a syringe are shown to be highly correlated with in situ kidney temperatures measured by fiberoptic probes. Statistically, the performance of the VUR detecting scheme is evaluated by error probabilities of making a wrong decision. Laboratory testing of the radiometric system supports the feasibility of passive non-invasive kidney thermometry for the detection of VUR classified within the two highest grades

  12. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours

    NASA Astrophysics Data System (ADS)

    Hornblower, V. D. M.; Yu, E.; Fenster, A.; Battista, J. J.; Malthaner, R. A.

    2007-01-01

    The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial 'tumours' were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the 'tumours' were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure 'tumour' volumes both in vivo and ex vivo.

  13. Dye-Free Porcine Model of Experimental Branch Retinal Vein Occlusion: A Suitable Approach for Retinal Proteomics

    PubMed Central

    Jørgensen Cehofski, Lasse; Kruse, Anders; Kjærgaard, Benedict; Stensballe, Allan; Honoré, Bent; Vorum, Henrik

    2015-01-01

    Branch retinal vein occlusion induces complex biological processes in the retina that are generated by a multitude of interacting proteins. These proteins and their posttranslational modifications can effectively be studied using modern proteomic techniques. However, no method for studying large-scale protein changes following branch retinal vein occlusion has been available until now. Obtainment of retinal tissue exposed to branch retinal vein occlusion is only available through experimental animal models. Traditional models of experimental branch retinal vein occlusion require the use of Rose Bengal dye combined with argon laser photocoagulation. The use of Rose Bengal dye is problematic in proteomic studies as the dye can induce multiple protein modifications when irradiated. This paper presents a novel technique for proteomic analysis of porcine retinal tissue with branch retinal vein occlusion combining a dye-free experimental model with label-free liquid chromatography mass spectrometry based proteomics. PMID:26064675

  14. Evaluation of a novel laparoscopic camera for characterization of renal ischemia in a porcine model using digital light processing (DLP) hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Olweny, Ephrem O.; Tan, Yung K.; Faddegon, Stephen; Jackson, Neil; Wehner, Eleanor F.; Best, Sara L.; Park, Samuel K.; Thapa, Abhas; Cadeddu, Jeffrey A.; Zuzak, Karel J.

    2012-03-01

    Digital light processing hyperspectral imaging (DLP® HSI) was adapted for use during laparoscopic surgery by coupling a conventional laparoscopic light guide with a DLP-based Agile Light source (OL 490, Optronic Laboratories, Orlando, FL), incorporating a 0° laparoscope, and a customized digital CCD camera (DVC, Austin, TX). The system was used to characterize renal ischemia in a porcine model.

  15. Cell Lineage Identification and Stem Cell Culture in a Porcine Model for the Study of Intestinal Epithelial Regeneration

    PubMed Central

    Gonzalez, Liara M.; Williamson, Ian; Piedrahita, Jorge A.; Blikslager, Anthony T.; Magness, Scott T.

    2013-01-01

    Significant advances in intestinal stem cell biology have been made in murine models; however, anatomical and physiological differences between mice and humans limit mice as a translational model for stem cell based research. The pig has been an effective translational model, and represents a candidate species to study intestinal epithelial stem cell (IESC) driven regeneration. The lack of validated reagents and epithelial culture methods is an obstacle to investigating IESC driven regeneration in a pig model. In this study, antibodies against Epithelial Adhesion Molecule 1 (EpCAM) and Villin marked cells of epithelial origin. Antibodies against Proliferative Cell Nuclear Antigen (PCNA), Minichromosome Maintenance Complex 2 (MCM2), Bromodeoxyuridine (BrdU) and phosphorylated Histone H3 (pH3) distinguished proliferating cells at various stages of the cell cycle. SOX9, localized to the stem/progenitor cells zone, while HOPX was restricted to the +4/‘reserve’ stem cell zone. Immunostaining also identified major differentiated lineages. Goblet cells were identified by Mucin 2 (MUC2); enteroendocrine cells by Chromogranin A (CGA), Gastrin and Somatostatin; and absorptive enterocytes by carbonic anhydrase II (CAII) and sucrase isomaltase (SIM). Transmission electron microscopy demonstrated morphologic and sub-cellular characteristics of stem cell and differentiated intestinal epithelial cell types. Quantitative PCR gene expression analysis enabled identification of stem/progenitor cells, post mitotic cell lineages, and important growth and differentiation pathways. Additionally, a method for long-term culture of porcine crypts was developed. Biomarker characterization and development of IESC culture in the porcine model represents a foundation for translational studies of IESC-driven regeneration of the intestinal epithelium in physiology and disease. PMID:23840480

  16. A porcine model of relief of unilateral ureteral obstruction: study on self-repairing capability over multiple time points.

    PubMed

    Liu, Yingying; Sun, Jing; Miao, Lining; Ji, Lei; Luo, Manyu; Li, Bing; Cui, Wenpeng; Wang, Yangwei; Xie, Yuansheng; Chen, Xiangmei

    2016-08-01

    It is still controversial whether renal tubular interstitial fibrosis (TIF) is a reversible process. Although previous studies examining TIF have been carried out in rodents, their kidney size and physiological character differ with humans, and the difference among diverse individuals before and after damage was obvious. Thus an experimental animal model to simulate human kidney disease was urged to be established. In order to clarify whether TIF is reversible, and the exact time points that the kidney has the capacity to be repaired, a porcine relief of unilateral ureteral obstruction (R-UUO) model was developed. Kidney damage and reparation were observed dynamically in vivo over various time points. Pigs were randomized divided into three groups (n = 6): UUO 5 days group, UUO 7 days, and UUO 10 days group. Each porcine in that groups underwent UUO and subsequent R-UUO for three time points. Renal function, histological structure, and protein expressions of α-smooth muscle actin (α-SMA), vimentin and E-cadherin were evaluated at different time points. Following R-UUO after 5 and 7 days of UUO, compared to UUO, serum creatinine levels were significantly decreased. Renal pathological tissue damage was repaired. The expressions of α-SMA and vimentin were decreased and E-cadherin expression was increased (P < 0.05). However, during R-UUO 14, 28, and 56 days after 10 days of UUO, serum creatinine was not decreased significantly. The expressions of α-SMA and vimentin consistently remained at high levels. Renal damage was unable to be restored and resulted in chronic lesions. Kidney damage induced by UUO can be reversed in early stages. However, longer time of UUO with significant levels of TIF showed limited reversibility. The porcine R-UUO model provides an ideal animal model for the investigation of kidney injury and repair as well as for the evaluation of the effect of drug treatment. PMID:27381184

  17. Intracapsular hip pressures in a porcine model: does position and volume matter?

    PubMed

    Hosalkar, Harish S; Varley, Eric S; Glaser, Diana A; Farnsworth, Christine L; Wenger, Dennis R

    2011-09-01

    This study outlines a relationship between joint volume, positioning, and intracapsular pressure in a healthy hip. After measuring the native intracapsular pressure in 12 porcine specimens, each joint was injected with radio-opaque-colored saline as pressures were measured. At 20 mmHg, the hip was placed in its position of ease and then in differing positions while pressures were recorded. Position significantly altered pressures, with the lowest values in neutral and the highest in hyperextension (P<0.001). Extreme hip positions may be detrimental because of high pressures created within the joint, possibly explaining complications associated with some hip diagnostic and treatment methods. PMID:21606854

  18. Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation.

    PubMed

    White, C W; Lillico, R; Sandha, J; Hasanally, D; Wang, F; Ambrose, E; Müller, A; Rachid, O; Li, Y; Xiang, B; Le, H; Messer, S; Ali, A; Large, S R; Lee, T W; Dixon, I M C; Lakowski, T M; Simons, K; Arora, R C; Tian, G; Nagendran, J; Hryshko, L V; Freed, D H

    2016-03-01

    Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation. PMID:26663659

  19. Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock.

    PubMed

    Nederhoed, Johanna H; Slikkerveer, Jeroen; Meyer, Klaas W; Wisselink, Willem; Musters, René J P; Yeung, Kak K

    2014-03-01

    Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs. PMID:24552914

  20. Semi-spherical Radiofrequency Bipolar Device - A New Technique for Liver Resection: Experimental In Vivo Study on the Porcine Model.

    PubMed

    Vavra, P; Penhaker, M; Jurcikova, J; Skrobankova, M; Crha, M; Ostruszka, P; Ihnat, P; Grepl, J; Delongova, P; Dvorackova, J; Prochazka, V; Salounova, D; Skoric, M; Rauser, P; Habib, N; Zonca, P

    2015-10-01

    The incidence of colorectal carcinoma is still growing in the Czech Republic and also all around the world. With success of oncological treatment is also growing a number of potential patients with liver metastases, who can profit from surgical therapy. The aim of this study was to confirm on porcine models that this method by using new surgical device is effective and safe for patients who have to undergo liver resection. The primary hypothesis of the study was to evaluate whether this new device is able to consistently produce homogeneous and predictable areas of coagulation necrosis without the Pringle maneuver of vascular inflow occlusion. The secondary hypothesis of the study was to compare the standard linear radiofrequency device and a new semi-spherical bipolar device for liver ablation and resection in a hepatic porcine model. Twelve pigs were randomly divided into two groups. Each pig underwent liver resection from both liver lobes in the marginal, thinner part of liver parenchyma. The pigs in first group were operated with standard using device and in the second group we used new developed semi-spherical device. We followed blood count in 0(th), 14(th) and 30(th) day from operation. 14(th) day from resection pigs underwent diagnostic laparoscopy to evaluate of their state, and 30(th) day after operation were all pigs euthanized and subjected to histopathological examination. Histopathological evaluation of thermal changes at the resection margin showed strong thermal alteration in both groups. Statistical analysis of collected dates did not prove any significant (p < 0.05) differences between standard using device and our new surgical tool. We proved safety of new designed semi-spherical surgical. This device can offer the possibility of shortening the ablation time and operating time, which is benefit for patients undergoing the liver resection. PMID:24945372

  1. Silver absorption on burns after the application of Acticoat: data from pediatric patients and a porcine burn model.

    PubMed

    Wang, Xue-Qing; Kempf, Margit; Mott, Jonathon; Chang, Hong-En; Francis, Rod; Liu, Pei-Yun; Cuttle, Leila; Olszowy, Henry; Kravchuk, Olena; Mill, Julie; Kimble, Roy M

    2009-01-01

    Silver dressings have been widely used to successfully prevent burn wound infection and sepsis. However, a few case studies have reported the functional abnormality and failure of vital organs, possibly caused by silver deposits. The aim of this study was to investigate the serum silver level in the pediatric burn population and also in several internal organs in a porcine burn model after the application of Acticoat. A total of 125 blood samples were collected from 46 pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had a mean peak serum silver level of 114 microg/L, whereas 10 patients with a mean of 1.85% TBSA burns had an undetectable level of silver (<5.4 microg/L). Overall, serum silver levels were closely related to burn sizes. However, the highest serum silver was 735 microg/L in a 15-month-old toddler with 10% TBSA burns and the second highest was 367 microg/L in a 3-year old with 28% TBSA burns. In a porcine model with 2% TBSA burns, the mean peak silver level was 38 microg/L at 2 to 3 weeks after application of Acticoat and was then significantly reduced to an almost undetectable level at 6 weeks. Of a total of four pigs, silver was detected in all four livers (1.413 microg/g) and all four hearts (0.342 microg/g), three of four kidneys (1.113 microg/g), and two of four brains (0.402 microg/g). This result demonstrated that although variable, the level of serum silver was positively associated with the size of burns, and significant amounts of silver were deposited in internal organs in pigs with only 2% TBSA burns, after application of Acticoat. PMID:19165102

  2. Efficacy of platelet-rich plasma as a shielding technique after endoscopic mucosal resection in rat and porcine models

    PubMed Central

    Lorenzo-Zúñiga, Vicente; Boix, Jaume; Moreno de Vega, Vicente; Bon, Ignacio; Marín, Ingrid; Bartolí, Ramón

    2016-01-01

    Background and study aims: The aims were to assess the efficacy of endoscopic application of Platelet-rich plasma (PRP) to prevent delayed perforation and to induce mucosal healing after endoscopic resections. Patients and methods: Colonic induced lesions were performed in rats (n = 16) and pigs (n = 4). Animals were randomized to receive onto the lesions saline (control) or PRP. Animals underwent endoscopic follow-up. Thermal injury was assessed with a 1 – 4 scale: (1) mucosal necrosis; (2) submucosal necrosis; (3) muscularis propria necrosis; and (4) serosal necrosis Results: Saline treatment showed 50 % of mortality in rats (P = 0.02). Mean ulcerated area after 48 hours and 7 days was significantly smaller with PRP than with saline (0.27 ± 0.02 cm2 and 0.08 ± 0.01 cm2 vs. 0.56 ± 0.1 cm2 and 0.40 ± 0.06 cm2; P < 0.001). The incidence of thermal injury was significantly lower with PRP (1.25 ± 0.46) than in controls (2.25 ± 0.50); P = 0.006. The porcine model showed a trend toward higher mucosal restoration in animals treated with PRP than with saline at weeks 1 and 2 (Median area in cm2: 0.55 and 0.40 vs. 1.32 and 0.79) Conclusions: Application of PRP to colonic mucosal lesions showed strong healing properties in rat and porcine models. PMID:27540573

  3. Pericytes support neutrophil transmigration via interleukin-8 across a porcine co-culture model of the blood-brain barrier.

    PubMed

    Pieper, Christian; Pieloch, Paulina; Galla, Hans-Joachim

    2013-08-01

    Transmigration of neutrophils across the blood-brain barrier (BBB) to an inflamed brain tissue is an important process during neuronal inflammation. The process of neutrophil activation as well as their way of rolling along the endothelium and their transmigration is quite well understood. Nevertheless, relatively little is known about the fate of neutrophils after they have transmigrated through the endothelium. The role of the other cells of the neurovascular unit in this process is also poorly understood. Here we studied the potential of pericytes to chemo-attract neutrophils under inflammatory conditions. Quantitative real time PCR, western blot analysis, and a chemotaxis assay showed that pericytes are able to chemo-attract neutrophils by interleukin-8 (IL-8) after stimulation with lipopolysaccharides (LPS), tumor necrosis factor-alpha (TNF-α), or interleukin-1beta (IL-1β). Then, a co-culture model consisting of primary porcine brain capillary endothelial cells (PBCECs) and primary porcine brain capillary pericytes (PBCPs) was used to analyze neutrophil transmigration across the BBB. As a model for inflammation, LPS was used and the effects of the cytokines TNF-α, IL-1β, and interferon-gamma (IFN-γ) were analyzed. In general, all stimulants apart from IFN-γ were able to increase transendothelial neutrophil migration. This effect was significantly reduced by a specific inhibitor of matrix metalloproteinases (MMPs)-2 and -9. MMP-2/-9 secretion is expected to decrease adhesion to pericytes and thus support the transmigration of neutrophils. Additionally, in an adhesion experiment, we showed that MMP-2/-9 inhibition significantly enhances the adhesion of neutrophils to pericytes. PMID:23769734

  4. Decolonisation of MRSA, S. aureus and E. coli by Cold-Atmospheric Plasma Using a Porcine Skin Model In Vitro

    PubMed Central

    Maisch, Tim; Shimizu, Tetsuji; Li, Yang-Fang; Heinlin, Julia; Karrer, Sigrid; Morfill, Gregor; Zimmermann, Julia L.

    2012-01-01

    In the last twenty years new antibacterial agents approved by the U.S. FDA decreased whereas in parallel the resistance situation of multi-resistant bacteria increased. Thus, community and nosocomial acquired infections of resistant bacteria led to a decrease in the efficacy of standard therapy, prolonging treatment time and increasing healthcare costs. Therefore, the aim of this work was to demonstrate the applicability of cold atmospheric plasma for decolonisation of Gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Methicillin-sensitive Staphylococcus aureus) and Gram-negative bacteria (E. coli) using an ex vivo pig skin model. Freshly excised skin samples were taken from six month old female pigs (breed: Pietrain). After application of pure bacteria on the surface of the explants these were treated with cold atmospheric plasma for up to 15 min. Two different plasma devices were evaluated. A decolonisation efficacy of 3 log10 steps was achieved already after 6 min of plasma treatment. Longer plasma treatment times achieved a killing rate of 5 log10 steps independently from the applied bacteria strains. Histological evaluations of untreated and treated skin areas upon cold atmospheric plasma treatment within 24 h showed no morphological changes as well as no significant degree of necrosis or apoptosis determined by the TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates for the first time that cold atmospheric plasma is able to very efficiently kill bacteria applied to an intact skin surface using an ex vivo porcine skin model. The results emphasize the potential of cold atmospheric plasma as a new possible treatment option for decolonisation of human skin from bacteria in patients in the future without harming the surrounding tissue. PMID:22558091

  5. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  6. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    PubMed Central

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H.S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for harvest of EPC in human cell therapy studies. In addition the therapeutic effects of paracrine factors secreted by these cells was evaluated in vitro and in vivo. Intracoronary injection of autologous porcine EPC was associated with increased infarct territory mass and improved regional ventricular systolic function at 2 months compared to control. Treatment with conditioned media derived from autologous EPC was associated with similar improved effects on infarct territory mass and function. Histologic analysis of the infarct territory revealed significantly increased cardiomyocyte size in EPC and conditioned media treated groups, when compared to controls. A paracrine EPC effect was also verified in a pure myocardial preparation in which cardiomyocytes devoid of fibroblast, neuronal and vascular elements directly responded by increasing cell mass when exposed to the same conditioned media. Analysis of conditioned media revealed elevated levels of TGFβ1 (human 267.3±11.8 pg/ml, porcine 57.1±6.1 pg/ml), a recognized mediator of hypertrophic signaling in the heart. Neutralizing antibodies to TGFβ1 attenuated the pro-hypertrophic effect of conditioned media, and use of recombinant TGFβ1 added to fresh media replicated the pro-hypertrophic effects of conditioned media in vitro. These data demonstrate the potential of paracrine factors secreted from endothelial progenitor cells to induce cardiomyocyte hypertrophy contributing to increased infarct territory LV mass, with

  7. Enzymolysis kinetics, thermodynamics and model of porcine cerebral protein with single-frequency countercurrent and pulsed ultrasound-assisted processing.

    PubMed

    Zou, Ye; Ding, Yangyang; Feng, Weiwei; Wang, Wei; Li, Qian; Chen, Yao; Wu, Huiyu; Wang, Xintong; Yang, Liuqing; Wu, Xiangyang

    2016-01-01

    The present work investigated the enzymolysis kinetics, thermodynamics and model of porcine cerebral protein (PCP) which was pretreated by single-frequency countercurrent and pulsed ultrasound. The kinetic constants for ultrasonic pretreated and traditional enzymolysis have been determined. Results showed that the value of KM in ultrasonic PCP (UPCP) enzymolysis decreased by 9% over that in the traditional enzymolysis. The values of reaction rate constant (k) for UPCP enzymolysis increased by 207%, 121%, 62%, and 45% at 293, 303, 313 and 323 K, respectively. For the thermodynamic parameters, ultrasound decreased activation energy (Ea), change in enthalpy (ΔH) and entropy (ΔS) by 76%, 82% and 31% in PCP, respectively. However, ultrasound had little change in Gibbs free energy (ΔG) value in the temperature range of 293-323 K. Therefore, a general kinetic equation for the enzymolysis model of UPCP by a simple empirical equation was suggested. The experimental values fits with the enzymolysis kinetic model with a low average relative error (4%) confirmed that the kinetic model was accurate to reflect the enzymolysis process. The positive effect of single-frequency countercurrent and pulsed ultrasound in this study and application of the kinetic model may be useful for the release of bioactive peptides from meat processing by-products. PMID:26384911

  8. Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models.

    PubMed

    Tullberg, Cecilia; Larsson, Karin; Carlsson, Nils-Gunnar; Comi, Irene; Scheers, Nathalie; Vegarud, Gerd; Undeland, Ingrid

    2016-03-01

    In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy-trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 μM of MDA, 0.96 μM of HHE, and 1.6 μM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 μM of MDA; 0.16, and 0.026 μM of HHE; 0.23, and 0.005 μM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies. PMID:26838473

  9. Evaluation of intravascular microdialysis for continuous blood glucose monitoring in hypoglycemia: an animal model.

    PubMed

    Schierenbeck, Fanny; Wallin, Mats; Franco-Cereceda, Anders; Liska, Jan

    2014-07-01

    We have previously shown that intravascular microdialysis in a central vein is an accurate method for continuous glucose monitoring in patients undergoing cardiac surgery. However, no hypoglycemia occurred in our earlier studies, prompting further evaluation of the accuracy of intravascular microdialysis in the hypoglycemic range. Thus, this animal study was performed. A porcine model was developed; hypoglycemia was induced using insulin injections. The pigs were monitored with intravascular microdialysis integrated in a triple-lumen central venous catheter. As reference, venous blood gas samples were taken every 5 minutes and analyzed in a blood gas analyzer. Ethical permission for the animal experiments was obtained from the Stockholm Regional Ethical Committee, reference no N397/09. A total of 213 paired samples were obtained for analysis, and 126 (59.2%) of these were in the hypoglycemic range (<74 mg/dl). Using Clarke error grid analysis, 100% of the paired samples were in region AB and 99% in region A. The ISO standard (ISO15197) was met. Bland-Altman analysis showed bias (mean difference) ± limits of agreement was -0.18 ± 16.2 mg/dl. No influence from glucose infusions was seen. The microdialysis monitoring system was found to be very responsive in rapid changes in blood glucose concentration. This study shows that intravascular microdialysis in a central vein is an accurate method for continuous glucose monitoring in hypoglycemia in a porcine experimental model. Furthermore, the system was not influenced by glucose administration and was found to be responsive in rapid blood glucose fluctuations. PMID:24876424

  10. In-vivo tissue repair using light-activated surgical adhesive in a porcine model

    NASA Astrophysics Data System (ADS)

    McNally-Heintzelman, Karen M.; Riley, Jill N.; Dickson, Tonya J.; Hou, Dong Ming; Rogers, Pamela; March, Keith L.

    2001-05-01

    An in vivo study was conducted to investigate the feasibility, mechanical function, and chronic biocompatibility of a new light-activated surgical adhesive for achieving rapid hemostasis of the puncture site following diagnostic catheterization and interventional cardiac procedures. Porcine carotid arteries (nequals6) and femoral arteries (nequals6) were exposed, and an incision was made in the arterial walls using a 16G needle. The surgical adhesive, composed of a poly(L-lactic-co-glycolic acid) scaffold doped with the traditional protein solder mix of serum albumin and indocyanine green dye, was used to close the incisions in conjunction with an 805-nm diode laser. Blood flow was restored to the vessels immediately after the procedure and the incision sites were checked for patency. The strength and hemostatic abilities of the new surgical adhesive were evaluated in the context of arterial pressure, persistence of hemostatis and presence of any inflammatory reaction after 3 days. After this evaluation period, the surgical procedure was repeated on the carotid arteries (nequals6) and femoral arteries (nequals6) of three additional animals that had been heparinized prior to surgery to closer approximate the conditions seen in a typical vascular surgical setting.

  11. Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

    SciTech Connect

    Deodhar, Ajita; Monette, Sebastien; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Solomon, Stephen B.

    2011-12-15

    Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent 'pores' in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

  12. Investigating detrusor muscle concentrations of oxybutynin after intravesical delivery in an ex vivo porcine model.

    PubMed

    Williams, Nicholas A; Lee, Kay M; Allender, Chris J; Bowen, Jenna L; Gumbleton, Mark; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

    2015-07-01

    Intravesical oxybutynin is highly effective in the treatment of overactive bladder. Traditionally the mechanism of action was explained by antagonism of muscarinic receptors located in the detrusor, however evidence now suggests antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL(-1) oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted drug quantified. Drug distribution into the urothelium, lamina propria and detrusor was determined. Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial Kp = 1.36 × 10(-5) cm s(-1) ). After 60 min intravesical instillation, concentrations achieved in the urothelium (298.69 μg g(-1) ) and lamina propria (43.65 μg g(-1) ) but not the detrusor (0.93 μg g(-1) ) were greater than reported IC50 values for oxybutynin. This work adds to the increasing body of evidence suggesting antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction. PMID:25989054

  13. Using heterogeneity in the population structure of U.S. swine farms to compare transmission models for porcine epidemic diarrhoea

    PubMed Central

    O’Dea, Eamon B.; Snelson, Harry; Bansal, Shweta

    2016-01-01

    In 2013, U.S. swine producers were confronted with the disruptive emergence of porcine epidemic diarrhoea (PED). Movement of animals among farms is hypothesised to have played a role in the spread of PED among farms. Via this or other mechanisms, the rate of spread may also depend on the geographic density of farms and climate. To evaluate such effects on a large scale, we analyse state-level counts of outbreaks with variables describing the distribution of farm sizes and types, aggregate flows of animals among farms, and an index of climate. Our first main finding is that it is possible for a correlation analysis to be sensitive to transmission model parameters. This finding is based on a global sensitivity analysis of correlations on simulated data that included a biased and noisy observation model based on the available PED data. Our second main finding is that flows are significantly associated with the reports of PED outbreaks. This finding is based on correlations of pairwise relationships and regression modeling of total and weekly outbreak counts. These findings illustrate how variation in population structure may be employed along with observational data to improve understanding of disease spread. PMID:26947420

  14. Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms.

    PubMed

    Yang, Qingping; Phillips, Priscilla L; Sampson, Edith M; Progulske-Fox, Ann; Jin, Shouguang; Antonelli, Patrick; Schultz, Gregory S

    2013-01-01

    Bacterial biofilms have been proposed to be a major factor contributing to the failure of chronic wounds to heal because of their increased tolerance to antimicrobial agents and the prolonged inflammation they cause. Phenotypic characteristics of bacterial biofilms vary depending on the substratum to which they attach, the nutritional environment, and the microorganisms within the biofilm community. To develop an ex vivo biofilm model that more closely mimics biofilms in chronic skin wounds, we developed an optimal procedure to grow mature biofilms on a central partial-thickness wound in 12-mm porcine skin explants. Chlorine gas produced optimal sterilization of explants while preserving histological properties of the epidermis and dermis. Pseudomonas aeruginosa and Staphylococcus aureus developed mature biofilms after 3 days that had dramatically increased tolerance to gentamicin and oxacillin (∼100× and 8,000× minimal inhibitory concentration, respectively) and to sodium hypochlorite (0.6% active chlorine). Scanning electron microscopy and confocal microscopy verified extensive exopolymeric biofilm structures on the explants. Despite a significant delay, a ΔlasI quorum-sensing mutant of P. aeruginosa developed biofilm as antibiotic-tolerant as wild-type after 3 days. This ex vivo model simulates growth of biofilms on skin wounds and provides an accurate model to assess effects of antimicrobial agents on mature biofilms. PMID:23927831

  15. Hybrid Modeling Improves Health and Performance Monitoring

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Scientific Monitoring Inc. was awarded a Phase I Small Business Innovation Research (SBIR) project by NASA's Dryden Flight Research Center to create a new, simplified health-monitoring approach for flight vehicles and flight equipment. The project developed a hybrid physical model concept that provided a structured approach to simplifying complex design models for use in health monitoring, allowing the output or performance of the equipment to be compared to what the design models predicted, so that deterioration or impending failure could be detected before there would be an impact on the equipment's operational capability. Based on the original modeling technology, Scientific Monitoring released I-Trend, a commercial health- and performance-monitoring software product named for its intelligent trending, diagnostics, and prognostics capabilities, as part of the company's complete ICEMS (Intelligent Condition-based Equipment Management System) suite of monitoring and advanced alerting software. I-Trend uses the hybrid physical model to better characterize the nature of health or performance alarms that result in "no fault found" false alarms. Additionally, the use of physical principles helps I-Trend identify problems sooner. I-Trend technology is currently in use in several commercial aviation programs, and the U.S. Air Force recently tapped Scientific Monitoring to develop next-generation engine health-management software for monitoring its fleet of jet engines. Scientific Monitoring has continued the original NASA work, this time under a Phase III SBIR contract with a joint NASA-Pratt & Whitney aviation security program on propulsion-controlled aircraft under missile-damaged aircraft conditions.

  16. Numerical modeling for underground nuclear test monitoring

    NASA Astrophysics Data System (ADS)

    Taylor, Steven R.; Kamm, James R.

    The symposium for Numerical Modeling for Underground Nuclear Test Monitoring was held March 23-25 in Durango, Colo. Funded by the DOE Office of Arms Control and Nonproliferation (OACN) and hosted by the Source Region Program at Los Alamos National Laboratory (LANL), the meetings's purpose was to discuss the state-of-the-art in numerical simulations of nuclear explosion phenomenology with applications to test-ban monitoring. In particular, we wished to focus on the uniqueness of model fits to data, the measurement and characterization of material response models, advanced modeling techniques, and applications of modeling to monitoring problems.The concept for the meeting arose through discussions with Marv Denny, who was on assignment at Department of Energy Headquarters from Lawrence Livermore National Laboratory (LLNL). In these conversations, the following question was discussed: how are numerical modeling techniques being used to understand the effects of explosion- source phenomenology on test-ban treaty monitoring? Numerical studies are becoming increasingly important in the evaluation of capabilities for proliferation monitoring; this trend has accelerated with the curtailment of the nuclear testing program. During these discussions, the issue of the uniqueness and limitations of numerical models arose. It was decided to address these questions by convening a group of experts to present and discuss the problems associated with modeling of close-in data from explosions.

  17. Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model.

    PubMed

    Lim, Kyung Seob; Park, Jun-Kyu; Jeong, Myung Ho; Bae, In-Ho; Nah, Jae-Woon; Park, Dae Sung; Kim, Jong Min; Kim, Jung Ha; Lee, So Youn; Jang, Eun Jae; Jang, Suyoung; Kim, Hyun Kuk; Sim, Doo Sun; Park, Keun-Ho; Hong, Young Joon; Ahn, Youngkeun; Kang, Jung Chaee

    2016-04-01

    The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78% in BMS vs. 51.5 ± 12.20% in AES vs. 34.7 ± 7.23% in SES vs. 28.7 ± 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 ± 7.88% in BMS vs. 50.4 ± 14.87% in AES vs. 34.5 ± 7.22% in SES vs. 28.9 ± 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia. PMID:26886814

  18. In-vivo regional myocardial perfusion measurements in a porcine model by ECG-gated multislice computed tomography

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Liang, Yun; Meyer, Cristopher A.; Teague, Shawn; Stecker, Michael; Hutchins, Gary; McLennan, Gordon; Persohn, Scott

    2003-05-01

    Purpose: To evaluate whether functional multi-slice computed tomography (MSCT) can identify regional areas of normally perfused and ischemic myocardium in a porcine model. Material and Methods: Three out bred pigs, two of which had ameroids surgically implanted to constrict flow within the LAD and LCx coronary arteries, were injected with 25 mL of iopromide (Isovue) at a rate of 5 mL/second via the femoral or jugular vein. Sixty axial scans along the short axis of the heart was acquired on a 16-slice CT scanner (Philips MX8000-IDT) triggered at end-diastole of the cardiac cycle and acquiring an image within 270 msec. A second series of scans were taken after an intravenous injection of a vasodilator, 150 μg/kg/min of adenosine. ROIs were drawn around the myocardial tissue and the resulting time-density curves were used to extract perfusion values. Results: Determination of the myocardial perfusion and fractional blood volume implementing three different perfusion models. A 5-point averaging or 'smoothing' algorithm was employed to effectively filter the data due to its noisy nature. The (preliminary) average perfusion and fractional blood volume values over selected axial slices for the pig without an artificially induced stenosis were measured to be 84 +/- 22 mL/min/100g-tissue and 0.17 +/- 0.04 mL/g-tissue, the former is consistent with PET scan and EBCT results. The pig with a stenosis in the left LAD coronary artery showed a reduced global perfusion value -- 45 mL/min/100g-tissue. Correlations in regional perfusion values relative to the stenosis were weak. During the infusion of adenosine, averaged perfusion values for the three subjects increased by 46 (+/-45) percent, comparable to increases measured with PET. Conclusion: Quantifying global perfusion values using MDCT appear encouraging. Future work will focus resolving the systematic effects from noise due to signal fluctuation from the porcine tachyardia (80-93 BPM) and provide a more robust measurement

  19. Mechanical Intestinal Obstruction in a Porcine Model: Effects of Intra-Abdominal Hypertension. A Preliminary Study

    PubMed Central

    Sánchez-Margallo, F. M.; Latorre, R.; López-Albors, O.; Wise, R.; Malbrain, M. L. N. G.; Castellanos, G.

    2016-01-01

    Introduction Mechanical intestinal obstruction is a disorder associated with intra-abdominal hypertension and abdominal compartment syndrome. As the large intestine intraluminal and intra-abdominal pressures are increased, so the patient’s risk for intestinal ischaemia. Previous studies have focused on hypoperfusion and bacterial translocation without considering the concomitant effect of intra-abdominal hypertension. The objective of this study was to design and evaluate a mechanical intestinal obstruction model in pigs similar to the human pathophysiology. Materials and Methods Fifteen pigs were divided into three groups: a control group (n = 5) and two groups of 5 pigs with intra-abdominal hypertension induced by mechanical intestinal obstruction. The intra-abdominal pressures of 20 mmHg were maintained for 2 and 5 hours respectively. Hemodynamic, respiratory and gastric intramucosal pH values, as well as blood tests were recorded every 30 min. Results Significant differences between the control and mechanical intestinal obstruction groups were noted. The mean arterial pressure, cardiac index, dynamic pulmonary compliance and abdominal perfusion pressure decreased. The systemic vascular resistance index, central venous pressure, pulse pressure variation, airway resistance and lactate increased within 2 hours from starting intra-abdominal hypertension (p<0.05). In addition, we observed increased values for the peak and plateau airway pressures, and low values of gastric intramucosal pH in the mechanical intestinal obstruction groups that were significant after 3 hours. Conclusion The mechanical intestinal obstruction model appears to adequately simulate the pathophysiology of intestinal obstruction that occurs in humans. Monitoring abdominal perfusion pressure, dynamic pulmonary compliance, gastric intramucosal pH and lactate values may provide insight in predicting the effects on endorgan function in patients with mechanical intestinal obstruction. PMID

  20. Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes

    NASA Astrophysics Data System (ADS)

    Cain, Clarence P.; Polhamus, Garrett D.; Roach, William P.; Stolarski, David J.; Schuster, Kurt J.; Stockton, Kevin; Rockwell, Benjamin A.; Chen, Bo; Welch, Ashley J.

    2006-07-01

    With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 µs) at 24-h postexposure are measured to be 99 and 83 Jcm-2 for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 Jcm-2 for a 5-mm-diam top-hat laser pulse.

  1. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

    PubMed Central

    Kloster, Brian O.; Lund, Lars; Lindholt, Jes S.

    2016-01-01

    Background The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. Methods The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. Results All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. Conclusion In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms. PMID:27144001

  2. Increased survival time after delayed histamine and prostaglandin blockade in a porcine model of severe sepsis-induced lung injury.

    PubMed

    Byrne, K; Sielaff, T D; Michna, B; Carey, P D; Blocher, C R; Vasquez, A; Sugerman, H J

    1990-03-01

    A combination of cimetidine, diphenhydramine, and ibuprofen has been shown to be an effective treatment in a porcine model of septic acute lung injury. The present study was designed to evaluate this therapy in a delayed treatment survival model. Three groups of animals were studied: a control group (C, n = 6) received a sham infusion of 0.9% saline; a septic group (Ps, n = 5) received a continuous infusion of live Pseudomonas aeruginosa organisms; and a treatment group (CID, n = 6) received P. aeruginosa plus cimetidine 150 mg, ibuprofen 12.5 mg/kg, and diphenhydramine 10 mg/kg given at 90 min after P. aeruginosa infusion, and hourly thereafter. Group Ps developed fulminant acute lung injury and hypodynamic septic shock. CID therapy ameliorated temporarily the progressive course of hypoxemia and increased extravascular lung water (EVLW), delayed the onset of cardiovascular deterioration, and improved significantly survival time. It was concluded that CID therapy given at 90 min after the onset of lethal continuous P. aeruginosa infusion improved significantly animal survival time by improving temporarily hypoxemia and increase in EVLW and delaying cardiovascular collapse. PMID:2302957

  3. Penile enhancement using a porcine small intestinal submucosa graft in a rat model.

    PubMed

    Leungwattanakij, S; Pummangura, N; Ratana-Olarn, K

    2006-01-01

    Several biodegradable materials have been experimented for penile enhancement, but none show the potential for clinical use. This study was designed to use porcine small intestinal submucosa (SIS) augmenting the normal tunica albuginea to increase the functional girth of the rat penis. In all, 20 adult male Sprague-Dawley rats constituted the study population. The animals were divided into two groups: group 1 consisted of the control (n=10) and group 2 (n=10) consisted of rats that underwent penile enhancement by a longitudinal I-shaped incision of the tunica albuginea on both sides, and the dissection of the plane between tunica albuginea and cavernosal tissue was carried out (n=10). The incision was then patched with a 3 x 10 mm2 piece of SIS, using a 6/0 nylon suture material. The penile length and mid-circumference were then measured using a Vernier Caliper before and 2 months after surgery. All rat penises underwent histological examination using Masson's trichome and Verhoff's van Giesen's stain for collagen and elastic fibers. The penile length, mid-circumference and degree of fibrosis score were expressed as mean+/-s.e. (standard error) and analyzed using a Wilcoxon rank-sum test. A statistical significance was accepted at P-value < or =0.05. Our results showed similar preoperative penile length and circumference in both groups. However, 2 months after the surgery, the mean penile circumference of the SIS group has grown significantly larger than the control group, while the mean penile length remained unchanged. The histological study of the rat penises revealed minimal amounts of fibrosis under the graft, and the elastic fibers of the graft showed orientation in a circular manner. In conclusion, SIS appears promising for material use in a penile enhancement. PMID:16049525

  4. Is intervertebral disc pressure linked to herniation?: An in-vitro study using a porcine model.

    PubMed

    Noguchi, Mamiko; Gooyers, Chad E; Karakolis, Thomas; Noguchi, Kimihiro; Callaghan, Jack P

    2016-06-14

    Approximately 40% of low back pain cases have been attributed to internal disc disruption. This disruption mechanism may be linked to intradiscal pressure changes, since mechanical loading directly affects the pressure and the stresses that the inner annulus fibrosus experiences. The objective of this study was to characterize cycle-varying changes in four dependent measures (intradiscal pressure, flexion-extension moments, specimen height loss, and specimen rotation angle) using a cyclic flexion-extension (CFE) loading protocol known to induce internal disc disruption. A novel bore-screw pressure sensor system was used to instrument 14 porcine functional spinal units. The CFE loading protocol consisted of 3600 cycles of flexion-extension range of motion (average 18.30 (SD 3.76) degrees) at 1Hz with 1500N of compressive load. On average, intradiscal pressure and specimen height decreased by 47% and 62%, respectively, and peak moments increased by 102%. From 900 to 2100 cycles, all variables exhibited significant changes between successive time points, except for the specimen posture at maximum pressure, which demonstrated a significant shift towards flexion limit after 2700 cycles. There were no further changes in pressure range after 2100 cycles, whereas peak moments and height loss were significantly different from prior time points throughout the CFE protocol. Twelve of the 14 specimens showed partial herniation; however, injury type was not significantly correlated to any of the dependent measures. Although change in pressure was not predictive of damage type, the increase in pressure range seen during this protocol supports the premise that repetitive combined loading (i.e., radial compression, tension and shear) imposes damage to the inner annulus fibrosus, and its failure mechanism may be linked to fatigue. PMID:27157242

  5. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model

    PubMed Central

    Horst, K.; Eschbach, D.; Pfeifer, R.; Relja, B.; Sassen, M.; Steinfeldt, T.; Wulf, H.; Vogt, N.; Frink, M.; Ruchholtz, S.; Pape, H. C.; Hildebrand, F.

    2016-01-01

    Background Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. Materials & Methods Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA. Results Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h. Conclusion A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application. PMID:27144532

  6. Relationship between retrograde coronary blood flow and the extent of no-reflow and infarct size in a porcine ischemia-reperfusion model.

    PubMed

    Stavrakis, Stavros; Terrovitis, John; Tsolakis, Elias; Drakos, Stavros; Dalianis, Argirios; Bonios, Michael; Koudoumas, Dimitrios; Malliaras, Konstantinos; Nanas, John

    2011-02-01

    Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia-reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30 min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2 h of reperfusion predicted a larger IA (r = 0.71; p = 0.001). Time-to-development of retrograde CBF was inversely related to IA (r = -0.55; p = 0.019) and NR (r = -0.62; p = 0.006). A larger IA (OR 1.12, 95% CI 1.01-1.24, p = 0.037) and NR (OR 1.09, 95% CI 1.01-1.18, p = 0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level. PMID:21153063

  7. Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model.

    PubMed

    Sielaff, T D; Sugerman, H J; Tatum, J L; Blocher, C R

    1987-08-01

    , ibuprofen, is effective and essential in the treatment of hypoxemia, early pulmonary hypertension, and pulmonary microvascular injury in this fulminant model of porcine Pseudomonas ARDS. PMID:3112984

  8. Monitoring the influence of compression therapy on pathophysiology and structure of a swine scar model using multispectral imaging system

    NASA Astrophysics Data System (ADS)

    Ghassemi, Pejhman; Travis, Taryn E.; Shuppa, Jeffrey W.; Moffatt, Lauren T.; Ramella-Romana, Jessica C.

    2014-03-01

    Scar contractures can lead to significant reduction in function and inhibit patients from returning to work, participating in leisure activities and even render them unable to provide care for themselves. Compression therapy has long been a standard treatment for scar prevention but due to the lack of quantifiable metrics of scar formation scant evidence exists of its efficacy. We have recently introduced a multispectral imaging system to quantify pathophysiology (hemoglobin, blood oxygenation, melanin, etc) and structural features (roughness and collagen matrix) of scar. In this study, hypertrophic scars are monitored in-vivo in a porcine model using the imaging system to investigate influence of compression therapy on its quality.

  9. Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model

    PubMed Central

    Guzman-Bautista, Edgar R; Garcia-Ruiz, Carlos E; Gama-Espinosa, Alicia L; Ramirez-Estudillo, Carmen; Rojas-Gomez, Oscar I; Vega-Lopez, Marco A

    2014-01-01

    Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA)-specific MatAb on the anti-OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti-OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination. PMID:24754050

  10. Synthesis and anti-staphylococcal activity of TiO2 nanoparticles and nanowires in ex vivo porcine skin model.

    PubMed

    Nataraj, Namrata; Anjusree, G S; Madhavan, Asha Anish; Priyanka, P; Sankar, Deepthi; Nisha, N; Lakshmi, S V; Jayakumar, R; Balakrishnan, Avinash; Biswas, Raja

    2014-05-01

    Staphylococcus aureus is one of the major causes of skin and soft tissue infections. In this study we compared the antimicrobial activity of two different TiO2 nanoformulations against Staphylococcus aureus. We synthesized TiO2 nanoparticles of approximately 80 nm diameter and TiO2 nanowires of approximately 100 nm diameter. Both nanoformulations possess anti-microbial activity; were non-hemolytic and cytocompatible. However, the anti-staphylococcal activity of TiO2 nanowires was better than the nanoparticles. In broth culture, growth of S. aureus was only partially inhibited by 2% and 4 wt% TiO2 nanoparticles and completely inhibited by TiO2 nanowires till 24 h. TiO2 nanowires treated S. aureus cells exhibits diminished membrane potential than nanoparticle treated cells. The anti-microbial properties of both TiO2 nanoformulations were validated using ex vivo porcine skin model which supplements the in vitro assays. Anti-bacterial activity of the TiO2 nanowires were also validated against multi drug resistant pathogenic strains of S. aureus, showing the clinical potency of the TiO2 nanowires compared to its nanoparticles. PMID:24734539

  11. Hepatic and Splenic Stiffness Augmentation Assessed with MR Elastography in an in vivo Porcine Portal Hypertension Model

    PubMed Central

    Yin, Meng; Kolipaka, Arunark; Woodrum, David A.; Glaser, Kevin J.; Romano, Anthony J; Manduca, Armando; Talwalkar, Jayant A.; Araoz, Philip A.; McGee, Kiaran P.; Anavekar, Nandan S.; Ehman, Richard L.

    2013-01-01

    Purpose To investigate the influence of portal pressure on the shear stiffness of the liver and spleen in a well-controlled in vivo porcine model with MR Elastography (MRE). A significant correlation between portal pressure and tissue stiffness could be used to noninvasively assess increased portal venous pressure (portal hypertension), which is a frequent clinical condition caused by cirrhosis of the liver and is responsible for the development of many lethal complications. Materials and Methods During multiple intra-arterial infusions of Dextran-40 in three adult domestic pigs in vivo, 3-D abdominal MRE was performed with left ventricle and portal catheters measuring blood pressure simultaneously. Least-squares linear regressions were used to analyze the relationship between tissue stiffness and portal pressure. Results Liver and spleen stiffness have a dynamic component that increases significantly following an increase in portal or left ventricular pressure. Correlation coefficients with the linear regressions between stiffness and pressure exceeded 0.8 in most cases. Conclusion The observed stiffness-pressure relationship of the liver and spleen could provide a promising noninvasive method for assessing portal pressure. Using MRE to study the tissue mechanics associated with portal pressure may provide new insights into the natural history and pathophysiology of hepatic diseases and may have significant diagnostic value in the future. PMID:23418135

  12. Enamel pathology resulting from loss of function in the cystic fibrosis transmembrane conductance regulator in a porcine animal model.

    PubMed

    Chang, Eugene H; Lacruz, Rodrigo S; Bromage, Timothy G; Bringas, Pablo; Welsh, Michael J; Zabner, Joseph; Paine, Michael L

    2011-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a phosphorylation- and ATP-regulated anion channel. CFTR expression and activity is frequently associated with an anion exchanger (AE) such as AE2 coded by the Slc4a2 gene. Mice null for Cftr and mice null for Slc4a2 have enamel defects, and there are some case reports of enamel anomalies in patients with CF. In this study we demonstrate that both Cftr and AE2 expression increased significantly during the rat enamel maturation stage versus the earlier secretory stage (5.6- and 2.9-fold, respectively). These qPCR data im- ply that there is a greater demand for Cl(-) and bicarbonate (HCO₃⁻) transport during the maturation stage of enamel formation, and that this is, at least in part, provided by changes in Cftr and AE2 expression. In addition, the enamel phenotypes of 2 porcine models of CF, CFTR-null, and CFTR-ΔF508 have been examined using backscattered electron microscopy in a scanning electron microscope. The enamel of newborn CFTR-null and CFTR-ΔF508 animals is hypomineralized. Together, these data provide a molecular basis for interpreting enamel disease associated with disruptions to CFTR and AE2 expression. PMID:21525720

  13. Enamel Pathology Resulting from Loss of Function in the Cystic Fibrosis Transmembrane Conductance Regulator in a Porcine Animal Model

    PubMed Central

    Chang, Eugene H.; Lacruz, Rodrigo S.; Bromage, Timothy G.; Bringas, Pablo; Welsh, Michael J.; Zabner, Joseph; Paine, Michael L.

    2011-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), a phosphorylation- and ATP-regulated anion channel. CFTR expression and activity is frequently associated with an anion exchanger (AE) such as AE2 coded by the Slc4a2 gene. Mice null for Cftr and mice null for Slc4a2 have enamel defects, and there are some case reports of enamel anomalies in patients with CF. In this study we demonstrate that both Cftr and AE2 expression increased significantly during the rat enamel maturation stage versus the earlier secretory stage (5.6- and 2.9-fold, respectively). These qPCR data im- ply that there is a greater demand for Cl– and bicarbonate (HCO3–) transport during the maturation stage of enamel formation, and that this is, at least in part, provided by changes in Cftr and AE2 expression. In addition, the enamel phenotypes of 2 porcine models of CF, CFTR-null, and CFTR-ΔF508 have been examined using backscattered electron microscopy in a scanning electron microscope. The enamel of newborn CFTR-null and CFTR-ΔF508 animals is hypomineralized. Together, these data provide a molecular basis for interpreting enamel disease associated with disruptions to CFTR and AE2 expression. PMID:21525720

  14. ICG angiography predicts burn scarring within 48 h of injury in a porcine vertical progression burn model.

    PubMed

    Fourman, Mitchell S; McKenna, Peter; Phillips, Brett T; Crawford, Laurie; Romanelli, Filippo; Lin, Fubao; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Singer, Adam J; Clark, Richard A F

    2015-08-01

    The current standard of care in determining the need to excise and graft a burn remains with the burn surgeon, whose clinical judgment is often variable. Prior work suggests that minimally invasive perfusion technologies are useful in burn prognostication. Here we test the predictive capabilities of Laser Doppler Imaging (LDI) and indocyanine green dye (ICG) angiography in the prediction of burn scarring 28 days after injury using a previously validated porcine burn model that shows vertical progression injury. Twelve female Yorkshire swine were burned using a 2.5 × 2.5 cm metal bar at variable temperature and application times to create distinct burn depths. Six animals (48 injuries total) each were analyzed with LDI or ICG angiography at 1, 24, 48, and 72 h following injury. A linear regression was then performed correlating perfusion measurements against wound contraction at 28 days after injury. ICG angiography showed a peak linear correlate (r(2)) of .63 (95% CI .34 to .92) at 48 h after burn. This was significantly different from the LDI linear regression (p < .05), which was measured at r(2) of .20 (95% CI .02 to .39). ICG angiography linear regression was superior to LDI at all timepoints. Findings suggest that ICG angiography may have significant potential in the prediction of long-term burn outcomes. PMID:25499407

  15. Integrating model abstraction into monitoring strategies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed and performed to investigate the opportunities and benefits of integrating model abstraction techniques into monitoring strategies. The study focused on future applications of modeling to contingency planning and management of potential and actual contaminant release sites wi...

  16. Implementation of a 3D porcine lumbar finite element model for the simulation of monolithic spinal rods with variable flexural stiffness.

    PubMed

    Brummund, Martin; Brailovski, Vladimir; Facchinello, Yann; Petit, Yvan; Mac-Thiong, Jean-Marc

    2015-08-01

    Monolithic superelastic-elastoplastic spinal rods (MSER) are promising candidates to provide (i) dynamic stabilisation in spinal segments prone to mechanical stress concentration and adjacent segment disease and (ii) to provide fusion-ready stabilization in spinal segments at risk of implant failure. However, the stiffness distributions along the rod's longitudinal axis that best meet clinical requirements remain unknown. The present study is part of a mixed numerical experimental research project and aims at the implementation of a 3D finite element model of the porcine lumbar spine to study the role of MSER material properties and stiffness distributions on the intradiscal pressure distribution in the adjacent segment. In this paper, preliminary intradiscal pressure predictions obtained at one functional spinal unit are presented. Due to a lack of porcine material property data, these predictions were obtained on the basis of uncalibrated human vertebral disc data which were taken from the literature. The results indicate that human annulus and nucleus data predict experimental porcine in vivo and in vitro data reasonably well for the compressive forces of varying magnitudes. PMID:26736412

  17. Efficacy of a bio-electric dressing in healing deep, partial-thickness wounds using a porcine model .

    PubMed

    Harding, Andrew C; Gil, Joel; Valdes, Jose; Solis, Michael; Davis, Stephen C

    2012-09-01

    Numerous physical modalities have been used in attempts to augment the healing process, including ultrasound, low- energy light therapy, and electrical stimulation (ES). ES has been shown to benefit tissue repair in a variety of wound types, but variations in study designs, administration, and parameters render its application in clinical practice somewhat unconventional. A dressing was designed to generate an electric potential of 0.6 V to 0.7 V in the presence of moisture, thereby delivering a sustained micro-current without the need for an external power source. The purpose of this study was to examine the effects of this bio-electric dressing (BED) on deep, partial-thickness wounds using six female specific pathogen-free animals and a well established porcine model for wound healing. Wounds (10 mm x 7 mm x 0.5 mm) were created in paravertebral and thoracic areas of these animals using a specialized electrokeratome and covered with the active polyester BED and a polyurethane film dressing (n = 30) (treatment) or an inactive polyester and film dressing (n = 30). Using an epidermal migration assay, wounds were assessed daily from day 4 through day 8 post-wounding. Differences in the proportion of wounds healed were statistically significant (P <0.001) on days 5 and 6 post-wounding. These results show BED is more effective than a control dressing treatment with moisture-retentive dressings in this animal model. Controlled clinical studies are warranted to elucidate the potential clinical implications of this treatment modality. PMID:22933701

  18. Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

    PubMed

    Axelsson, Birger; Häggmark, Sören; Svenmarker, Staffan; Johansson, Göran; Gupta, Anil; Tydén, Hans; Wouters, Patrick; Haney, Michael

    2016-09-01

    It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. PMID:26837238

  19. Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock.

    PubMed

    Bambakidis, Ted; Dekker, Simone E; Sillesen, Martin; Liu, Baoling; Johnson, Craig N; Jin, Guang; de Vries, Helga E; Li, Yongqing; Alam, Hasan B

    2016-08-15

    Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2 h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300 mg/kg, n = 5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis® (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p < 0.001), natural killer cell communication (p < 0.001), and dendritic cell maturation (p < 0.001). DAVID analysis indicated that a cluster of inflammatory pathways held the highest rank and gene enrichment score. Real-time PCR data confirmed that VPA significantly down-expressed genes that ultimately regulate nuclear factor-kB (NF-kB)-mediated production of cytokines, such as TYROBP, TREM2, CCR1, and IL-1β. This high-throughput analysis of cerebral gene expression shows that addition of VPA to the resuscitation protocol significantly modulates the expression of inflammatory pathways in a clinically realistic model of TBI+HS. PMID:26905959

  20. System monitoring and diagnosis with qualitative models

    NASA Technical Reports Server (NTRS)

    Kuipers, Benjamin

    1991-01-01

    A substantial foundation of tools for model-based reasoning with incomplete knowledge was developed: QSIM (a qualitative simulation program) and its extensions for qualitative simulation; Q2, Q3 and their successors for quantitative reasoning on a qualitative framework; and the CC (component-connection) and QPC (Qualitative Process Theory) model compilers for building QSIM QDE (qualitative differential equation) models starting from different ontological assumptions. Other model-compilers for QDE's, e.g., using bond graphs or compartmental models, have been developed elsewhere. These model-building tools will support automatic construction of qualitative models from physical specifications, and further research into selection of appropriate modeling viewpoints. For monitoring and diagnosis, plausible hypotheses are unified against observations to strengthen or refute the predicted behaviors. In MIMIC (Model Integration via Mesh Interpolation Coefficients), multiple hypothesized models of the system are tracked in parallel in order to reduce the 'missing model' problem. Each model begins as a qualitative model, and is unified with a priori quantitative knowledge and with the stream of incoming observational data. When the model/data unification yields a contradiction, the model is refuted. When there is no contradiction, the predictions of the model are progressively strengthened, for use in procedure planning and differential diagnosis. Only under a qualitative level of description can a finite set of models guarantee the complete coverage necessary for this performance. The results of this research are presented in several publications. Abstracts of these published papers are presented along with abtracts of papers representing work that was synergistic with the NASA grant but funded otherwise. These 28 papers include but are not limited to: 'Combined qualitative and numerical simulation with Q3'; 'Comparative analysis and qualitative integral representations

  1. Geophysical Models for Nuclear Explosion Monitoring

    SciTech Connect

    Pasyanos, M E; Walter, W R; Flanagan, M

    2003-07-16

    Geophysical models are increasingly recognized as an important component of regional calibrations for seismic monitoring. The models can be used to predict geophysical measurements, such as body wave travel times, and can be derived from direct regional studies or even by geophysical analogy. While empirical measurements of these geophysical parameters might be preferred, in aseismic regions or regions without seismic stations, this data might not exist. In these cases, models represent a 'best guess' of the seismic properties in a region, which improves on global models such as the PREM (Preliminary Reference Earth Model) or the IASPEI (International Association of Seismology and Physics of the Earth's Interior) models. The model-based predictions can also serve as a useful background for the empirical measurements by removing trends in the data. To this end, Lawrence Livermore National Laboratory (LLNL) has developed the WENA model for Western Eurasia and North Africa. This model is constructed using a regionalization of several dozen lithospheric (crust and uppermost mantle) models, combined with the Laske sediment model and 3SMAC upper mantle. We have evaluated this model using a number of data sets, including travel times, surface waves, receiver functions, and waveform analysis. Similarly, Los Alamos National Laboratory (LANL) has developed a geophysical model for East Asia, allowing LLNL/LANL to construct a model for all of Eurasia and North Africa. These models continue to evolve as new and updated datasets are used to critically assess the predictive powers of the model. Research results from this meeting and other reports and papers can be used to update and refine the regional boundaries and regional models. A number of other groups involved in monitoring have also developed geophysical models. As these become available, we will be assessing the models and their constitutive components for their suitability for inclusion in the National Nuclear Security

  2. GULF OF MEXICO HYPOXIA MONITORING AND MODELING

    EPA Science Inventory

    Greene, Richard M. and Russell G. Kreis. In press. Gulf of Mexico Hypoxia Monitoring and Modeling (Abstract). To be presented at the EPA Science Forum: Healthy Communities and Ecosystems, 1-3 June 2004, Washington, DC. 1 p. (ERL,GB R990).

    Oxygen-depleted or hypoxic bottom...

  3. Monitoring issues from a modeling perspective

    NASA Technical Reports Server (NTRS)

    Mahlman, Jerry D.

    1993-01-01

    Recognition that earth's climate and biogeophysical conditions are likely changing due to human activities has led to a heightened awareness of the need for improved long-term global monitoring. The present long-term measurement efforts tend to be spotty in space, inadequately calibrated in time, and internally inconsistent with respect to other instruments and measured quantities. In some cases, such as most of the biosphere, most chemicals, and much of the ocean, even a minimal monitoring program is not available. Recently, it has become painfully evident that emerging global change issues demand information and insights that the present global monitoring system simply cannot supply. This is because a monitoring system must provide much more than a statement of change at a given level of statistical confidence. It must describe changes in diverse parts of the entire earth system on regional to global scales. It must be able to provide enough input to allow an integrated physical characterization of the changes that have occurred. Finally, it must allow a separation of the observed changes into their natural and anthropogenic parts. The enormous policy significance of global change virtually guarantees an unprecedented level of scrutiny of the changes in the earth system and why they are happening. These pressures create a number of emerging challenges and opportunities. For example, they will require a growing partnership between the observational programs and the theory/modeling community. Without this partnership, the scientific community will likely fall short in the monitoring effort. The monitoring challenge before us is not to solve the problem now, but rather to set appropriate actions in motion so as to create the required framework for solution. Each individual piece needs to establish its role in the large problem and how the required interactions are to take place. Below, we emphasize some of the needs and opportunities that could and should be

  4. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock

    PubMed Central

    Palágyi, Péter; Kaszaki, József; Rostás, Andrea; Érces, Dániel; Németh, Márton; Boros, Mihály; Molnár, Zsolt

    2015-01-01

    Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n = 9) and shock groups (n = 27). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r = −0.65, p < 0.0001), CPR (r = −0.64, p < 0.0001), central venous oxygen saturation (r = −0.50, p < 0.0001), and central venous-to-arterial PCO2 difference (r = 0.62, p < 0.0001). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock. PMID:26504837

  5. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock.

    PubMed

    Palágyi, Péter; Kaszaki, József; Rostás, Andrea; Érces, Dániel; Németh, Márton; Boros, Mihály; Molnár, Zsolt

    2015-01-01

    Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n = 9) and shock groups (n = 27). Hemorrhagic shock was induced by reducing mean arterial pressure (MAP) to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60-180 min). Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV) and capillary perfusion rate (CPR) were assessed by orthogonal polarization spectral (OPS) imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap), which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r = -0.65, p < 0.0001), CPR (r = -0.64, p < 0.0001), central venous oxygen saturation (r = -0.50, p < 0.0001), and central venous-to-arterial PCO2 difference (r = 0.62, p < 0.0001). This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock. PMID:26504837

  6. Quantitative analysis of Porcine Reproductive and Respiratory Syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant viral disease facing the global swine industry. Viremia profiles of PRRS virus challenged pigs reflect the severity and progression of the infection within the host and provide crucial information for subsequen...

  7. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft

    PubMed Central

    Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.

    2015-01-01

    Background Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis. Methods A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries. Results No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft

  8. Dose reduction assessment in dynamic CT myocardial perfusion imaging in a porcine balloon-induced-ischemia model

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2014-03-01

    We investigated the use of an advanced hybrid iterative reconstruction (IR) technique (iDose4, Philips Health- care) for low dose dynamic myocardial CT perfusion (CTP) imaging. A porcine model was created to mimic coronary stenosis through partial occlusion of the left anterior descending (LAD) artery with a balloon catheter. The severity of LAD occlusion was adjusted with FFR measurements. Dynamic CT images were acquired at end-systole (45% R-R) using a multi-detector CT (MDCT) scanner. Various corrections were applied to the acquired scans to reduce motion and imaging artifacts. Absolute myocardial blood flow (MBF) was computed with a deconvolution-based approach using singular value decomposition (SVD). We compared a high and a low dose radiation protocol corresponding to two different tube-voltage/tube-current combinations (80kV p/100mAs and 120kV p/150mAs). The corresponding radiation doses for these protocols are 7.8mSv and 34.3mSV , respectively. The images were reconstructed using conventional FBP and three noise-reduction strengths of the IR method, iDose. Flow contrast-to-noise ratio, CNRf, as obtained from MBF maps, was used to quantitatively evaluate the effect of reconstruction on contrast between normal and ischemic myocardial tissue. Preliminary results showed that the use of iDose to reconstruct low dose images provide better or comparable CNRf to that of high dose images reconstructed with FBP, suggesting significant dose savings. CNRf was improved with the three used levels of iDose compared to FBP for both protocols. When using the entire 4D dynamic sequence for MBF computation, a 77% dose reduction was achieved, while considering only half the scans (i.e., every other heart cycle) allowed even further dose reduction while maintaining relatively higher CNRf.

  9. Ultrasound-guided tissue fractionation by high intensity focused ultrasound in an in vivo porcine liver model.

    PubMed

    Khokhlova, Tatiana D; Wang, Yak-Nam; Simon, Julianna C; Cunitz, Bryan W; Starr, Frank; Paun, Marla; Crum, Lawrence A; Bailey, Michael R; Khokhlova, Vera A

    2014-06-01

    The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has been recently gaining momentum. In HIFU, ultrasound energy from an extracorporeal source is focused within the body to ablate tissue at the focus while leaving the surrounding organs and tissues unaffected. Most HIFU therapies are designed to use heating effects resulting from the absorption of ultrasound by tissue to create a thermally coagulated treatment volume. Although this approach is often successful, it has its limitations, such as the heat sink effect caused by the presence of a large blood vessel near the treatment area or heating of the ribs in the transcostal applications. HIFU-induced bubbles provide an alternative means to destroy the target tissue by mechanical disruption or, at its extreme, local fractionation of tissue within the focal region. Here, we demonstrate the feasibility of a recently developed approach to HIFU-induced ultrasound-guided tissue fractionation in an in vivo pig model. In this approach, termed boiling histotripsy, a millimeter-sized boiling bubble is generated by ultrasound and further interacts with the ultrasound field to fractionate porcine liver tissue into subcellular debris without inducing further thermal effects. Tissue selectivity, demonstrated by boiling histotripsy, allows for the treatment of tissue immediately adjacent to major blood vessels and other connective tissue structures. Furthermore, boiling histotripsy would benefit the clinical applications, in which it is important to accelerate resorption or passage of the ablated tissue volume, diminish pressure on the surrounding organs that causes discomfort, or insert openings between tissues. PMID:24843132

  10. A Comparison between splenic fossa and subhepatic fossa auxiliary partial heterotopic liver transplantation in a porcine model.

    PubMed

    Ai, Lemin; Liang, Xiao; Wang, Zhifei; Shen, Jie; Yu, Feiyan; Xie, Limei; Pan, Yongming; Lin, Hui

    2016-06-01

    To test the alternative possible locations for the placement of a liver graft and the relevant surgical technique issues, we developed a porcine model of auxiliary partial heterotopic liver transplantation (APHLT) and evaluated the difference between 2 styles of liver transplantation, either subhepatic fossa or splenic fossa APHLT, by comparing survival and biochemical indexes. Thirty-eight miniature pigs were randomly divided into 2 groups. A left hemihepatic graft without the middle hepatic vein (HV) was procured from the living donor. In group A (n = 9), an 8 mm diameter polytetrafluoroethylene (PTFE) graft approximately 2.5 cm long was connected to the left HV while another PTFE graft of the same size was connected to the left portal vein (PV). The liver graft was implanted in the right subhepatic fossa following splenectomy and right nephrectomy. In group B (n = 10), a PTFE graft of the same size was connected to the left HV while the liver graft was implanted in the splenic fossa following splenectomy and left nephrectomy. Survival rate and complications were observed at 2 weeks after transplantation. Data were collected from 5 animals in group A and 6 animals in group B that survived longer than 2 weeks. The liver function and renal function of the recipients returned to normal at 1 week after surgery in both groups. Eighty-eight percent (14/16) of the PTFE grafts remained patent at 2 weeks after surgery, but 44% of the PTFE grafts (7/16) developed mural thrombus. No significant differences in the survival rate and biochemistry were found between the 2 groups. In conclusion, the splenic fossa APHLT can achieve beneficial outcomes similar to the subhepatic fossa APHLT in miniature pigs, although it also has a high morbidity rate due to hepatic artery thrombosis, PV thrombosis, and PTEF graft mural thrombus formation. Liver Transplantation 22 812-821 2016 AASLD. PMID:26785299

  11. The influence of acute unloading on left ventricular strain and strain rate by speckle tracking echocardiography in a porcine model.

    PubMed

    Dahle, Geir Olav; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-05-15

    Noninvasive measurements of myocardial strain and strain rate by speckle tracking echocardiography correlate to cardiac contractile state but also to load, which may weaken their value as indices of inotropy. In a porcine model, we investigated the influence of acute dynamic preload reductions on left ventricular strain and strain rate and their relation to the pressure-conductance catheter-derived preload recruitable stroke work (PRSW) and peak positive first derivative of left ventricular pressure (LV-dP/dtmax). Speckle tracking strain and strain rate in the longitudinal, circumferential, and radial directions were measured during acute dynamic reductions of end-diastolic volume during three different myocardial inotropic states. Both strain and strain rate were sensitive to unloading of the left ventricle (P < 0.001), but the load dependency for strain rate was modest compared with strain. Changes in longitudinal and circumferential strain correlated more strongly to changes in end-diastolic volume (r = -0.86 and r = -0.72) than did radial strain (r = 0.35). Longitudinal, circumferential, and radial strain significantly correlated with LV-dP/dtmax (r = -0.53, r = -0.46, and r = 0.86), whereas only radial strain correlated with PRSW (r = 0.55). Strain rate in the longitudinal, circumferential and radial direction significantly correlated with both PRSW (r = -0.64, r = -0.58, and r = 0.74) and LV-dP/dtmax (r = -0.95, r = -0.70, and r = 0.85). In conclusion, the speckle tracking echocardiography-derived strain rate is more robust to dynamic ventricular unloading than strain. Longitudinal and circumferential strain could not predict load-independent contractility. Strain rates, and especially in the radial direction, are good predictors of preload-independent inotropic markers derived from conductance catheter. PMID:26968547

  12. Comparison of Pull-out Strength for Different Bone Block Length in a Porcine Anterior Cruciate Ligament Model

    PubMed Central

    Posner, Matthew; Owens, Brett; Johnson, Paul; Masciello, Noreen; Cameron, Kenneth; Roach, Christopher; Svoboda, Steven; Floersheim, Bruce

    2014-01-01

    Background: Bone block length for bone–patellar tendon–bone (BPTB) anterior cruciate ligament (ACL) reconstruction has traditionally been 25 mm in length. The previous surgical technique did not require the surgeon to pay particular attention to the length of the bone block, and therefore, there is scant evidence in the literature describing ideal lengths. With the gaining popularity of accessory medial portal drilling of the femoral tunnel, concerns with tunnel length and graft shuttling have surfaced. Newer techniques have advised shortening of the femoral bone block to accommodate the shorter tunnel and for ease of bone block manipulation into the aperture of the tunnel. Purpose: To compare the effects of bone block length on the pull-out strength of patellar tendon grafts using metal interference screws in a porcine ACL reconstruction model. The hypothesis was that the pull-out strength of each length of bone block under cyclic and ultimate load to failure testing would surpass the physiologic loads experienced by a normal ACL. Study Design: Controlled laboratory study. Methods: This study used 27 unmatched porcine femurs and BPTB constructs. Specimens were randomly assigned to a 10-, 15-, or 20-mm bone block reconstruction and a cycle load of 100, 500, or 1000 cycles. This resulted in 9 specimen groups with 3 specimens in each group. A central composite design (CCD) for the test matrix was selected, as this was optimum for requiring relatively few experiments while still exploring the complete range of interest for 2 independent variables. Each reconstruction used a 7 × 20–mm titanium interference screw. All reconstructions were performed on the femoral side using 10-mm-wide patellar tendon grafts, and tensile tests were performed. The loading protocol started with a 20-N preload, then cyclic testing to the appropriate number of cycles in the elastic region between 50 and 150 N at a strain rate of 200 mm/min, and then ended with ultimate load

  13. Myocardial ATP hydrolysis rates in vivo: a porcine model of pressure overload-induced hypertrophy

    PubMed Central

    Xiong, Qiang; Zhang, Pengyuan; Guo, Jing; Swingen, Cory; Jang, Albert

    2015-01-01

    Left ventricular (LV) hypertrophy (LVH) and congestive heart failure are accompanied by changes in myocardial ATP metabolism. However, the rate of ATP hydrolysis cannot be measured in the in vivo heart with the conventional techniques. Here, we used a double-saturation phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol to monitor ATP hydrolysis rate in swine hearts as the hearts became hypertrophic in response to aortic banding (AOB). Animals that underwent AOB (n = 22) were compared with animals that underwent sham surgery (n = 8). AOB induced severe LVH (cardiac MRI). LV function (ejection fraction and systolic thickening fraction) declined significantly, accompanied by deferent levels of pericardial effusion, and wall stress increased in aorta banded animals at week 1 after AOB, suggesting acute heart failure, which recovered by week 8 when concentric LVH restored LV wall stresses. Severe LV dysfunction was accompanied by corresponding declines in myocardial bioenergetics (phosphocreatine-to-ATP ratio) and in the rate of ATP production via creatine kinase at week 1. For the first time, the same linear relationships of the rate increase of the constants of the ATP hydrolysis rate (kATP→Pi) vs. the LV rate-pressure product increase during catecholamine stimulation were observed in vivo in both normal and LVH hearts. Collectively, these observations demonstrate that the double-saturation, phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol can accurately monitor myocardial ATP hydrolysis rate in the hearts of living animals. The severe reduction of LV chamber function during the acute phase of AOB is accompanied by the decrease of myocardial bioenergetic efficiency, which recovers as the compensated LVH restores the LV wall stresses. PMID:26024682

  14. Novel porcine repetitive elements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An analysis of 220 fully sequenced porcine BACs generated by the Comparative Vertebrate Sequencing Initiative (http://www.nisc.nih.gov/) revealed 27 distinct, novel porcine repetitive elements ranging in length from 55 to 1059 nucleotides. This set of fully sequenced BACs covers approximately 1% of...

  15. Cloning and characterization of porcine resistin gene.

    PubMed

    Dai, M H; Xia, T; Chen, X D; Gan, L; Feng, S Q; Qiu, H; Peng, Y; Yang, Z Q

    2006-02-01

    Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance. PMID:16023825

  16. Monitoring and Modelling Lakes and Coastal Environments

    NASA Astrophysics Data System (ADS)

    Odada, Eric

    2009-01-01

    The monitoring and modeling of lakes and coastal environments is becoming ever more important, particularly because these environments bear heavy loads in terms of human population, and their resources are critical to the livelihoods and well-being of coastal inhabitants and ecosystems. Monitoring and Modelling Lakes and Coastal Environments is a collection of 18 papers arising from the Lake 2004 International Conference on Conservation, Restoration and Management of Lakes and Coastal Wetlands, held in Bhubaneswar, Orissa, India, 9-13 December 2004. Consequently, 15 of the papers are concerned with studies on the Indian subcontinent, and many of the papers focus on India's Lake Chilika, the site of a special session during the conference. Two papers concern Japan, and one focuses on North America's Great Lakes region. Although the book has a regional bias, the replication of best practices that can be drawn from these studies may be useful for an international audience.

  17. Degradation Modelling for Health Monitoring Systems

    NASA Astrophysics Data System (ADS)

    Stetter, R.; Witczak, M.

    2014-12-01

    Condition-monitoring plays an increasingly important role for technical processes in order to improve reliability, availability, maintenance and lifetime of equipment. With increasing demands for efficiency and product quality, plus progress in the integration of automatic control systems in high-cost mechatronic and critical safety processes, the field of health monitoring is gaining interest. A similar research field is concerned with an estimation of the remaining useful life. A central question in these fields is the modelling of degradation; degradation is a process of a gradual and irreversible accumulation of damage which will finally result in a failure of the system. This paper is based on a current research project and explores various degradation modelling techniques. These results are explained on the basis of an industrial product - a system for the generation of health status information for pump systems. The result of this fuzzy-logic based system is a single number indicating the current health of a pump system.

  18. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

    PubMed Central

    Gao, Yi; Mu, Ning; Xu, Xiao-Ping; Wang, Yan

    2005-01-01

    changes. CONCLUSION: The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF. PMID:16222738

  19. Evidence of disseminated intravascular coagulation in a porcine model following radiation exposure

    NASA Astrophysics Data System (ADS)

    Krigsfeld, G. S.; Shah, J. B.; Sanzari, J. K.; Lin, L.; Kennedy, A. R.

    2014-10-01

    Recent evidence has suggested that disseminated intravascular coagulation (DIC) plays an integral role in death at the LD50 dose of either gamma or solar particle event (SPE)-like proton radiation in ferrets. In these studies, Yucatan minipigs were evaluated to determine whether they were susceptible to the development of radiation induced DIC. Yucatan minipigs were exposed to a dose of 2.5 Gray (Gy) with X-rays and monitored over the course of 30 days. Evidence of DIC was evaluated by way of thromboelastometry parameters, platelet counts, fibrinogen concentration, and the d-dimer assay. Pigs exposed to X-rays developed signs of DIC within 2 days' post-irradiation. The development of DIC was exacerbated over the course of the studies, and one of the pigs died at day 14 and another had to be euthanized on day 16 post-irradiation. For both of these pigs, DIC was evident at the time of death. The following observations were indicated or were suggestive of DIC: whole blood clotting was impaired (as evidenced by thromboelastometry alterations), there were decreased platelet counts, elevated d-dimer concentrations in the blood, and/or hemorrhaging and the presence of fibrin in tissues observed during post-mortem examination. The extrapolation of data from these studies, in combination with other published data, have led to the hypothesis that there could be a correlation between the propensity to develop DIC, as indicated by hemorrhaging at death at relatively low doses of radiation, and the LD50 for a particular species. Our data suggest that the development of DIC may contribute to death at the LD50 dose in large mammals.

  20. Evidence of Disseminated Intravascular Coagulation in a Porcine Model Following Radiation Exposure

    PubMed Central

    Krigsfeld, G.S.; Shah, J.B.; Sanzari, J.K.; Lin, L.; Kennedy, A.R.

    2014-01-01

    Recent evidence has suggested that disseminated intravascular coagulation (DIC) plays an integral role in death at the LD50 dose of either gamma or solar particle event (SPE)-like proton radiation in ferrets. In these studies, Yucatan minipigs were evaluated to determine whether they were susceptible to the development of radiation induced DIC. Yucatan minipigs were exposed to a dose of 2.5 Gray (Gy) with x-rays and monitored over the course of 30 days. Evidence of DIC was evaluated by way of thromboelastometry parameters, platelet counts, fibrinogen concentration, and the d-dimer assay. Pigs exposed to x-rays developed signs of DIC within 2 days post-irradiation. The development of DIC was exacerbated over the course of the studies, and one of the pigs died at day 14 and another had to be euthanized on day 16 post-irradiation. For both of these pigs, DIC was evident at the time of death. The following observations were indicated or were suggestive of DIC: whole blood clotting was impaired (as evidenced by thromboelastometry alterations), there were decreased platelet counts, elevated d-dimer concentrations in the blood, and/or hemorrhaging and the presence of fibrin in tissues observed during post-mortem examination. The extrapolation of data from these studies, in combination with other published data, have led to the hypothesis that there could be a correlation between the propensity to develop DIC, as indicated by hemorrhaging at death at relatively low doses of radiation, and the LD50 for a particular species. Our data suggest that the development of DIC may contribute to death at the LD50 dose in large mammals. PMID:25197627

  1. Generating a Natural Porcine Model of Gastrointestinal Food Allergy to Peanut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The peanut (Arachis hypogaea) is an extremely potent allergen and is one of the most life-threatening food sensitivities known. Peanuts cause the majority of food-related anaphylaxis in children, adolescents, and adults. There is no good animal model currently in place to study peanut allergies. Exp...

  2. Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1.

    PubMed

    Davis, Catherine C; Baccam, Mekhine; Mantz, Mary J; Osborn, Thomas W; Hill, Donna R; Squier, Christopher A

    2014-01-15

    Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen-TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ((3)H2O) through porcine vaginal mucosa was determined at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52°C) did not significantly increase flux of (3)H2O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of (3)H2O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment. PMID:24333258

  3. Porcine Sialoadhesin: A Newly Identified Xenogeneic Innate Immune Receptor

    PubMed Central

    Brock, Linda G.; Delputte, Peter L.; Waldman, Joshua P.; Nauwynck, Hans J.; Rees, Michael A.

    2012-01-01

    Extracorporeal porcine liver perfusion is being developed as a bridge to liver allotransplantation for patients with fulminant hepatic failure. This strategy is limited by porcine Kupffer cell destruction of human erythrocytes, mediated by lectin binding of a sialic acid motif in the absence of antibody and complement. Sialoadhesin, a macrophage restricted lectin that binds sialic acid, was originally described as a sheep erythrocyte binding receptor. Given similarities between sialoadhesin and the unidentified macrophage lectin in our model, we hypothesized porcine sialoadhesin contributed to recognition of human erythrocytes. Two additional types of macrophages were identified to bind human erythrocytes - spleen and alveolar. Expression of sialoadhesin was confirmed by immunofluorescence in porcine tissues and by flow cytometry on primary macrophages. A stable transgenic cell line expressing porcine sialoadhesin (pSn CHO) bound human erythrocytes, while a sialoadhesin mutant cell line did not. Porcine macrophage and pSn CHO recognition of human erythrocytes was inhibited approximately 90% by an anti-porcine sialoadhesin monoclonal antibody and by human erythrocyte glycoproteins. Furthermore, this binding was substantially reduced by sialidase treatment of erythrocytes. These data support the hypothesis that porcine sialoadhesin is a xenogeneic receptor that mediates porcine macrophage binding of human erythrocytes in a sialic acid-dependent manner. PMID:22958948

  4. Monitoring and modeling growing season dynamics

    NASA Astrophysics Data System (ADS)

    White, Michael Aaron

    Phenology, the study of recurring biological cycles and their connection to climate, is a growing field of global change research. Vegetation phenology exerts a strong control over carbon cycles, weather, and global radiation partitioning between sensible and latent heat fluxes. Phenological monitors of the timing and length of the growing season can also be used as barometers of vegetation responses to climatic variability. In the following chapters, I present research investigating the monitoring and interpretation of growing season dynamics. Ecological modeling is limited more by data availability than by model theory. In particular, the description of vegetation functional types (biomes) for distributed modeling has been lacking. In chapter 1, I present a documented description and sensitivity analysis of the 34 parameters used in the ecosystem model, BIOME-BGC, for major temperate biomes. I applied BIOME-BGC in the eastern U.S. deciduous broad leaf forest and found that minor phenological variation created large impacts on simulated net ecosystem exchange of carbon (chapter 2). In addition to simulating the effects of growing season variability, it is also important to develop accurate field monitoring techniques, both as a means of testing modeling activities and as a validation of satellite remote sensing estimates. I conducted an intercomparison of field techniques that could be used to monitor phenological dynamics in and ecosystems (chapter 3). I found that methodological barriers to rapid, low cost monitoring were severe, but that a digital camera with both visible and near-infrared channels was a viable option. Satellite remote sensing provides the only means of obtaining consistent estimates of phenological variation at a global scale, yet our understanding of these data has been limited by a lack of ground observations. To address this problem, I proposed, developed, and wrote a phenology measurement protocol for the Global Learning and Observations

  5. In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

    SciTech Connect

    Planche, Olivier; Teriitehau, Christophe; Boudabous, Sana; Robinson, Joey Marie; Rao, Pramod; Deschamps, Frederic; Farouil, Geoffroy; Baere, Thierry de

    2013-02-15

    To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularity of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.

  6. CT and MRI of experimentally induced mesenteric ischemia in a porcine model

    SciTech Connect

    Klein, H.M.; Seggewib, C.; Weghaus, P.; Kamp, M.; Guenther, R.W.

    1996-03-01

    Our goal was to assess the value of CT and MRI for the detection of bowel wall changes in experimentally induced mesenteric ischemia. In 18 female pigs. a percutaneous embolization of the superior mesenteric artery was performed with buthyl-2-cyanoacrylate and Lipoidal (1:1) (experimental group). In six animals, only diagnostic imaging and histologic evaluation were performed (control group). CT was carried out 3, 6, and 12 h after occlusion. Incremental CT (1 s scan time, 5 mm slice thickness, 7 mm increment, 120 kV/290 mAs) and spiral CT (slice thickness 5 mm, pitch 1.5, 120 kV/165 mA) were performed pre and post contrast injection (Somatom Plus/ Siemens). Serial CT was carried out after intravenous contrast injection (I ml/kg, 2 ml/s). MRI (Magnetom 1.5 T: Siemens) was performed with T1 (pre and post 0.01 mmol/kg Gd-DTPA; Magnevist; Schering. Germany), T2, and proton density images in axial orientation. Slice thickness was 3 mm and slice gap 1 mm. Additionally, a T1-weighted GE sequence was obtained in dynamic technique (before and 30, 60, and 90 s after contrast agent injection) with a slice thickness of 5 mm. Biometrical monitoring included blood pressure, heart frequency, blood cell count, electrolyte status, blood gas analysis, and determination of serum lactate. Image evaluation included morphological analysis and determination of the enhancement pattern. Histological specimens were obtained and analyzed according to the Chiu classification. The histologic workup of the specimen 3, 6, and 12 h after vascular occlusion revealed an average Chiu state 3, 4, and 5. On CT, the bowel wall had a thickness of 4.7 mm on average in the ischemic segments. There was a significant difference from the control group. Free intraperitoneal fluid and intramural gas were seen after 12 h of ischemia in 80%. In ischemic bowel segments, no mural enhancement was seen. Normal segments and the bowel of the control animals showed an enhancement of 34 HU on average.

  7. Establishment of a novel, eco-friendly transgenic pig model using porcine pancreatic amylase promoter-driven fungal cellulase transgenes.

    PubMed

    Lin, Y S; Yang, C C; Hsu, C C; Hsu, J T; Wu, S C; Lin, C J; Cheng, W T K

    2015-02-01

    Competition between humans and livestock for cereal and legume grains makes it challenging to provide economical feeds to livestock animals. Recent increases in corn and soybean prices have had a significant impact on the cost of feed for pig producers. The utilization of byproducts and alternative ingredients in pig diets has the potential to reduce feed costs. Moreover, unlike ruminants, pigs have limited ability to utilize diets with high fiber content because they lack endogenous enzymes capable of breaking down nonstarch polysaccharides into simple sugars. Here, we investigated the feasibility of a transgenic strategy in which expression of the fungal cellulase transgene was driven by the porcine pancreatic amylase promoter in pigs. A 2,488 bp 5'-flanking region of the porcine pancreatic amylase gene was cloned by the genomic walking technique, and its structural features were characterized. Using GFP as a reporter, we found that this region contained promoter activity and had the potential to control heterologous gene expression. Transgenic pigs were generated by pronuclear microinjection. Founders and offspring were identified by PCR and Southern blot analyses. Cellulase mRNA and protein showed tissue-specific expression in the pancreas of F1 generation pigs. Cellulolytic enzyme activity was also identified in the pancreas of transgenic pigs. These results demonstrated the establishment of a tissue-specific promoter of the porcine pancreatic amylase gene. Transgenic pigs expressing exogenous cellulase may represent a way to increase the intake of low-cost, fiber-rich feeds. PMID:25063310

  8. Amniotic Fluid-Derived Mesenchymal Stem Cells Prevent Fibrosis and Preserve Renal Function in a Preclinical Porcine Model of Kidney Transplantation

    PubMed Central

    Baulier, Edouard; Favreau, Frederic; Le Corf, Amélie; Jayle, Christophe; Schneider, Fabrice; Goujon, Jean-Michel; Feraud, Olivier; Bennaceur-Griscelli, Annelise; Turhan, Ali G.

    2014-01-01

    It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation. PMID:24797827

  9. Primary in vitro culture of porcine tracheal epithelial cells in an air-liquid interface as a model to study airway epithelium and Aspergillus fumigatus interactions.

    PubMed

    Khoufache, Khaled; Cabaret, Odile; Farrugia, Cécile; Rivollet, Danièle; Alliot, Annie; Allaire, Eric; Cordonnier, Catherine; Bretagne, Stéphane; Botterel, Françoise

    2010-12-01

    Since the airway epithelium is the first tissue encountered by airborne fungal spores, specific models are needed to study this interaction. We developed such a model using primary porcine tracheal epithelial cells (PTEC) as a possible alternative to the use of primary human cells. PTEC were obtained from pigs and were cultivated in an air-liquid interface. Fluorescent brightener was employed to quantify the internalization of Aspergillus fumigatus conidia. Potential differences (Vt) and transepithelial resistances (Rt) after challenge with the mycotoxin, verruculogen, were studied. Primers for porcine inflammatory mediator genes IL-8, TNF-alpha, and GM-CSF were designed for a quantitative real-time PCR procedure to study cellular responses to challenges with A. fumigatus conidia. TEM showed the differentiation of ciliated cells and the PTEC ability to internalize conidia. The internalization rate was 21.9 ± 1.4% after 8 h of incubation. Verruculogen (10(-6) M) significantly increased Vt without having an effect on the Rt. Exposure of PTEC to live A. fumigatus conidia for 24 h induced a 10- to 40-fold increase in the mRNA levels of inflammatory mediator genes. PTEC behave similarly to human cells and are therefore a suitable alternative to human cells for studying interaction between airway epithelium and A. fumigatus. PMID:20608777

  10. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    PubMed Central

    Kloster, Brian O.; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    Background A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. Methods 10 pigs (group A) underwent infrarenal aortic dissection, balloon dilatation, infusion of elastase into the lumen and placement of a stenosing cuff around the aorta. 10 control pigs (group B) underwent a sham procedure. The subsequent 28 days the AP-diameters of the aneurysms were measured using ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. Results In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11.33 ± 0.13 mm equivalent to 9.3% which was significantly less than in group A (p < 0.001). In group A, a significant negative association between the preoperative weight and the resulting AP-diameters was found. Histology shoved more or less complete resolution of the elastic tissue in the tunica media in group A. The most frequent complication was a neurological deficit in the lower limbs. Conclusion In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved, it's also a potential model for further studies of novel endovascular devices and their complications. PMID:25685342

  11. Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

    PubMed Central

    Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

    2013-01-01

    Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

  12. Dynamic myocardial perfusion in a porcine balloon-induced ischemia model using a prototype spectral detector CT

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Fares, Anas; Levi, Jacob; Wu, Hao; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Myocardial CT perfusion (CTP) imaging is an application that should greatly benefit from spectral CT through the significant reduction of beam hardening (BH) artifacts using mono-energetic (monoE) image reconstructions. We used a prototype spectral detector CT (SDCT) scanner (Philips Healthcare) and developed advanced processing tools (registration, segmentation, and deconvolution-based flow estimation) for quantitative myocardial CTP in a porcine ischemia model with different degrees of coronary occlusion using a balloon catheter. The occlusion severity was adjusted with fractional flow reserve (FFR) measurements. The SDCT scanner is a single source, dual-layer detector system, which allows simultaneous acquisitions of low and high energy projections, hence enabling accurate projection-based material decomposition and effective reduction of BH-artifacts. In addition, the SDCT scanner eliminates partial scan artifacts with fast (0.27s), full gantry rotation acquisitions. We acquired CTP data under different hemodynamic conditions and reconstructed conventional 120kVp images and projection-based monoenergetic (monoE) images for energies ranging from 55keV-to-120keV. We computed and compared myocardial blood flow (MBF) between different reconstructions. With balloon completely deflated (FFR=1), we compared the mean attenuation in a myocardial region of interest before iodine arrival and at peak iodine enhancement in the left ventricle (LV), and we found that monoE images at 70keV effectively minimized the difference in attenuation, due to BH, to less than 1 HU compared to 14 HU with conventional 120kVp images. Flow maps under baseline condition (FFR=1) were more uniform throughout the myocardial wall at 70keV, whereas with 120kVp data about 12% reduction in blood flow was noticed on BH-hypoattenuated areas compared to other myocardial regions. We compared MBF maps at different keVs under an ischemic condition (FFR < 0.7), and we found that flow

  13. Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

    PubMed Central

    Hanawa, Kenichiro; Ito, Kenta; Aizawa, Kentaro; Shindo, Tomohiko; Nishimiya, Kensuke; Hasebe, Yuhi; Tuburaya, Ryuji; Hasegawa, Hideyuki; Yasuda, Satoshi; Kanai, Hiroshi; Shimokawa, Hiroaki

    2014-01-01

    Background Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD. Methods and Results We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group. Conclusions These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. PMID:25111309

  14. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model.

    PubMed

    Wang, Jian; Zhou, DA-Qing; He, Meng; Li, Wen-Gang; Pang, Xiang; Yu, Xiao-Xiang; Jiang, Bo

    2013-05-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  15. Effects of renal pelvic high-pressure perfusion on nephrons in a porcine pyonephrosis model

    PubMed Central

    WANG, JIAN; ZHOU, DA-QING; HE, MENG; LI, WEN-GANG; PANG, XIANG; YU, XIAO-XIANG; JIANG, BO

    2013-01-01

    The aim of this study was to investigate the effects of various renal pelvic pressure gradients on nephrons with purulent infection. Five miniature test pigs were selected. One side of the kidney was used to prepare the pyonephrosis model and the other side was used as the healthy control. A piezometer and a water fill tube were inserted into the renal pelvis through the ureter. Prior to perfusion, punctures were made on the healthy and purulent sides of the kidneys to obtain tissues (as controls). Subsequently, a puncture biopsy was conducted on the kidneys at five pressure levels: 10, 20, 30, 40 and 50 mmHg. Once the renal pelvic pressure had increased, the healthy and injured kidneys presented pathological changes, including dilation of the renal tubule and capsule and compression of the renal glomerulus. When the renal pelvic pressure exceeded 20 mmHg, the injured kidney presented more damage. Electron microscopy revealed that the increase in pressure resulted in the following: the podocyte gap widened, the epithelial cells of the renal capsule separated from the basement membrane, the basement membrane thickness became uneven, the continuity of the basement membrane was interrupted at multiple positions and the renal tubule microvillus arrangement became disorganised. The manifestations in the pyonephrosis model were more distinct compared with those in the healthy kidney. As the renal pelvic pressure exceeds 20 mmHg under a renal purulent infection status, the nephrons become damaged. The extent of the damage is aggravated as the pressure is increased. PMID:23737886

  16. Edmund Prince Fowler Award Thesis. Evaluation of random skin flap survival in a porcine model.

    PubMed

    Pratt, M F

    1996-06-01

    The pathophysiology of random skin flap necrosis in the pig model was studied the effects of several drugs on skin flap survival were examined. The investigated drugs included acetylsalicylic acid (ASA), pentoxifylline (PTX), prostaglandin E2 (PGE2), and an experimental 21-aminosteroid, U-74389G. Each drug altered different parameters known to be associated with tissue necrosis. Demonstrated mechanisms of skin flap failure included the alteration of erythrocyte flexibility and platelet function and the activation of neutrophils with resultant accumulation of damaging oxygen-free radicals. Random skin flap survival did not improve with ASA but did improve significantly with PTX, PGE2, and U-74389G. The results of this study underscore the importance of neutrophil-mediated necrosis in the pathophysiology of skin flap failure. The data further demonstrate the need to develop drugs aimed at reversing or preventing the tissue damage from oxygen-free radicals in order to enhance the survival of random skin flaps. PMID:8656954

  17. The impact of force on the timing of bruises evaluated in a porcine model.

    PubMed

    Barington, Kristiane; Jensen, Henrik Elvang

    2016-05-01

    In animal models developed in order to estimate the age of bruises, focus has been on the changes over time and not considering the force used to inflict the trauma. In the present study, gross and histological changes in 2, 4, 6 and 8 h old bruises which were inflicted with a low, moderate and high force were compared. Twelve experimental pigs were randomly assigned to three groups of force (low, moderate and high force). All pigs were anesthetized, and on each animal four blunt traumas were inflicted on the back with the low, moderate or high force according to the groups. The pigs were kept in anesthesia for 2, 4, 6 or 8 h, after which they were euthanized, and skin and muscle tissues were sampled for histology. As control, two pigs were included. The gross appearance of bruises developed similarly until 0.5 h after infliction at which time the visibility of the bruises depended on the force. The infiltration of subcutaneous neutrophils depended on the time and force used which was confirmed by both manual evaluation and image analysis of immunostained skin sections. In the muscle tissue, the number of macrophages was found useful for age determination in bruises inflicted with the highest force. Therefore, when evaluating forensic cases of bruises in both human and veterinary pathology the impact of force and not only the timing should be taken into consideration. PMID:27085141

  18. A model aerosol exposure system for induction of porcine Haemophilus pleuropneumonia.

    PubMed Central

    Sebunya, T N; Saunders, J R; Osborne, A D

    1983-01-01

    One group of six pigs and another group of three pigs were separately exposed in a polyethylene enclosed chamber for ten minutes, respectively, to Haemophilus pleuropneumoniae serotype 1 and Bacillus subtilis aerosols generated by an ultrasonic nebulizer. Haemophilus pleuropneumoniae and B. subtilis were deposited throughout the lungs immediately following aerosol exposure. The number of H. pleuropneumoniae and B. subtilis deposited varied within and between lungs in each group. The mean numbers of both organisms deposited in the posterior (caudal and accessory) lobes were significantly greater than those in the anterior (cranial and middle) lobes (P less than 0.001). The four principals that received H. pleuropneumoniae aerosols and the two contact controls developed fatal fibrinous pneumonia which simulated that seen in natural infections. Since this exposure system consistently resulted in clinical disease it has good potential as a model for the study of pathogenesis of the disease and more specifically for the evaluation of vaccines. Images Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6403208

  19. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model.

    PubMed

    Sanzari, Jenine K; Diffenderfer, Eric S; Hagan, Sarah; Billings, Paul C; Gridley, Daila S; Seykora, John T; Kennedy, Ann R; Cengel, Keith A

    2015-07-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. PMID:26256624

  20. Acute hematological effects of solar particle event proton radiation in the porcine model.

    PubMed

    Sanzari, J K; Wan, X S; Wroe, A J; Rightnar, S; Cengel, K A; Diffenderfer, E S; Krigsfeld, G S; Gridley, D S; Kennedy, A R

    2013-07-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel. PMID:23672458

  1. Acute Hematological Effects of Solar Particle Event Proton Radiation in the Porcine Model

    PubMed Central

    Sanzari, J. K.; Wan, X. S.; Wroe, A. J.; Rightnar, S.; Cengel, K. A.; Diffenderfer, E. S.; Krigsfeld, G. S.; Gridley, D. S.; Kennedy, A. R.

    2013-01-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel. PMID:23672458

  2. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model

    NASA Astrophysics Data System (ADS)

    Sanzari, Jenine K.; Diffenderfer, Eric S.; Hagan, Sarah; Billings, Paul C.; Gridley, Daila S.; Seykora, John T.; Kennedy, Ann R.; Cengel, Keith A.

    2015-07-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed.

  3. Biomechanical investigation of impact induced rib fractures of a porcine infant surrogate model.

    PubMed

    Blackburne, William B; Waddell, J Neil; Swain, Michael V; Alves de Sousa, Ricardo J; Kieser, Jules A

    2016-09-01

    This study investigated the structural, biomechanical and fractographic features of rib fractures in a piglet model, to test the hypothesis that fist impact, apart from thoracic squeezing, may result in lateral costal fractures as observed in abused infants. A mechanical fist with an accelerometer was constructed and fixed to a custom jig. Twenty stillborn piglets in the supine position were impacted on the thoracic cage. The resultant force versus time curves from the accelerometer data showed a number of steps indicative of rib fracture. The correlation between impact force and number of fractures was statistically significant (Pearson׳s r=0.528). Of the fractures visualized, 15 completely pierced the parietal pleura of the thoracic wall, and 5 had butterfly fracture patterning. Scanning electron microscopy showed complete bone fractures, at the zone of impact, were normal to the axis of the ribs. Incomplete vertical fractures, with bifurcation, occurred on the periphery of the contact zone. This work suggests the mechanism of rib failure during a fist impact is typical of the transverse fracture pattern in the anterolateral region associated with cases of non-accidental rib injury. The impact events investigated have a velocity of ~2-3m/s, approximately 2×10(4) times faster than previous quasi-static axial and bending tests. While squeezing the infantile may induce buckle fractures in the anterior as well as posterior region of the highly flexible bones, a fist punch impact event may result in anterolateral transverse fractures. Hence, these findings suggest that the presence of anterolateral rib fractures may result from impact rather than manual compression. PMID:27310573

  4. Preclinical Evaluation of Tegaderm™ Supported Nanofibrous Wound Matrix Dressing on Porcine Wound Healing Model

    PubMed Central

    Ong, Chee Tian; Zhang, Yanzhong; Lim, Raymond; Samsonraj, Rebekah; Masilamani, Jeyakumar; Phan, Tran Hong Ha; Ramakrishna, Seeram; Lim, Ivor; Kee, Irene; Fahamy, Mohammad; Templonuevo, Vilma; Lim, Chwee Teck; Phan, Toan Thang

    2015-01-01

    Objective: Nanofibers for tissue scaffolding and wound dressings hold great potential in realizing enhanced healing of wounds in comparison with conventional counterparts. Previously, we demonstrated good fibroblast adherence and growth on a newly developed scaffold, Tegaderm™-Nanofiber (TG-NF), made from poly ɛ-caprolactone (PCL)/gelatin nanofibers electrospun onto Tegaderm (TG). The purpose of this study is to evaluate the performance and safety of TG-NF dressings in partial-thickness wound in a pig healing model. Approach: To evaluate the rate of reepithelialization, control TG, human dermal fibroblast-seeded TG-NF(+) and -unseeded TG-NF(−) were randomly dressed onto 80 partial-thickness burns created on four female and four male pigs. Wound inspections and dressings were done after burns on day 7, 14, 21, and 28. On day 28, full-thickness biopsies were taken for histopathological evaluation by Masson-Trichrome staining for collagen and hematoxylin–eosin staining for cell counting. Results: No infection and severe inflammation were recorded. Wounds treated with TG-NF(+) reepithelialized significantly faster than TG-NF(−) and control. Wound site inflammatory responses to study groups were similar as total cell counts on granulation tissues show no significant differences. Most of the wounds completely reepithelialized by day 28, except for two wounds in control and TG-NF(−). A higher collagen coverage was also recorded in the granulation tissues treated with TG-NF(+). Innovation and Conclusion: With better reepithelialization achieved by TG-NF(+) and similar rates of wound closure by TG-NF(−) and control, and the absence of elevated inflammatory responses to TG-NF constructs, TG-NF constructs are safe and demonstrated good healing potentials that are comparable to Tegaderm. PMID:25713753

  5. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model

    PubMed Central

    Sanzari, Jenine K.; Diffenderfer, Eric S.; Hagan, Sarah; Billings, Paul C.; Gridley, Daila S.; Seykora, John T.; Kennedy, Ann R.; Cengel, Keith A.

    2015-01-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the dermis upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. PMID:26256624

  6. Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

    PubMed Central

    Stecher, David; Bronkers, Glenn; Noest, Jappe O.T.; Tulleken, Cornelis A.F.; Hoefer, Imo E.; van Herwerden, Lex A.; Pasterkamp, Gerard; Buijsrogge, Marc P.

    2014-01-01

    To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated. PMID:25490000

  7. Interactive real-time mapping and catheter ablation of the cavotricuspid isthmus guided by magnetic resonance imaging in a porcine model

    PubMed Central

    Hoffmann, Boris A.; Koops, Andreas; Rostock, Thomas; Müllerleile, Kai; Steven, Daniel; Karst, Roman; Steinke, Mark U.; Drewitz, Imke; Lund, Gunnar; Koops, Susan; Adam, Gerhard; Willems, Stephan

    2010-01-01

    Aims We investigated the feasibility of real-time magnetic resonance imaging (RTMRI) guided ablation of the cavotricuspid isthmus (CTI) by using a MRI-compatible ablation catheter. Methods and results Cavotricuspid isthmus ablation was performed in an interventional RTMRI suite by using a novel 7 French, steerable, non-ferromagnetic ablation catheter in a porcine in vivo model (n = 20). The catheter was introduced and navigated by RTMRI visualization only. Catheter position and movement during manipulation were continuously visualized during the entire intervention. Two porcine prematurely died due to VT/VF. Anatomical completion of the CTI ablation line could be achieved after a mean of 6.3±3 RF pulses (RF energy: 1807±1016.4 Ws/RF pulse, temperature: 55.9±5.9°C) in n = 18 animals. In 15 of 18 procedures (83.3%) a complete CTI block was proven by conventional mapping in the electrophysiological (EP) lab. Conclusion Completely non-fluoroscopic ablation guided by RTMRI using a steerable and non-ferromagnetic catheter is a promising novel technology in interventional electrophysiology. PMID:19897495

  8. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system.

    PubMed

    Fahmi, Rachid; Eck, Brendan L; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G; Wilson, David L

    2016-03-21

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR [Formula: see text] 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition

  9. Quantitative myocardial perfusion imaging in a porcine ischemia model using a prototype spectral detector CT system

    NASA Astrophysics Data System (ADS)

    Fahmi, Rachid; Eck, Brendan L.; Levi, Jacob; Fares, Anas; Dhanantwari, Amar; Vembar, Mani; Bezerra, Hiram G.; Wilson, David L.

    2016-03-01

    We optimized and evaluated dynamic myocardial CT perfusion (CTP) imaging on a prototype spectral detector CT (SDCT) scanner. Simultaneous acquisition of energy sensitive projections on the SDCT system enabled projection-based material decomposition, which typically performs better than image-based decomposition required by some other system designs. In addition to virtual monoenergetic, or keV images, the SDCT provided conventional (kVp) images, allowing us to compare and contrast results. Physical phantom measurements demonstrated linearity of keV images, a requirement for quantitative perfusion. Comparisons of kVp to keV images demonstrated very significant reductions in tell-tale beam hardening (BH) artifacts in both phantom and pig images. In phantom images, consideration of iodine contrast to noise ratio and small residual BH artifacts suggested optimum processing at 70 keV. The processing pipeline for dynamic CTP measurements included 4D image registration, spatio-temporal noise filtering, and model-independent singular value decomposition deconvolution, automatically regularized using the L-curve criterion. In normal pig CTP, 70 keV perfusion estimates were homogeneous throughout the myocardium. At 120 kVp, flow was reduced by more than 20% on the BH-hypo-enhanced myocardium, a range that might falsely indicate actionable ischemia, considering the 0.8 threshold for actionable FFR. With partial occlusion of the left anterior descending (LAD) artery (FFR  <  0.8), perfusion defects at 70 keV were correctly identified in the LAD territory. At 120 kVp, BH affected the size and flow in the ischemic area; e.g. with FFR ≈ 0.65, the anterior-to-lateral flow ratio was 0.29  ±  0.01, over-estimating stenosis severity as compared to 0.42  ±  0.01 (p  <  0.05) at 70 keV. On the non-ischemic inferior wall (not a LAD territory), the flow ratio was 0.50  ±  0.04 falsely indicating an actionable ischemic condition in a healthy

  10. Georeferenced model simulations efficiently support targeted monitoring

    NASA Astrophysics Data System (ADS)

    Berlekamp, Jürgen; Klasmeier, Jörg

    2010-05-01

    The European Water Framework Directive (WFD) demands the good ecological and chemical status of surface waters. To meet the definition of good chemical status of the WFD surface water concentrations of priority pollutants must not exceed established environmental quality standards (EQS). Surveillance of the concentrations of numerous chemical pollutants in whole river basins by monitoring is laborious and time-consuming. Moreover, measured data do often not allow for immediate source apportionment which is a prerequisite for defining promising reduction strategies to be implemented within the programme of measures. In this context, spatially explicit model approaches are highly advantageous because they provide a direct link between local point emissions (e.g. treated wastewater) or diffuse non-point emissions (e.g. agricultural runoff) and resulting surface water concentrations. Scenario analyses with such models allow for a priori investigation of potential positive effects of reduction measures such as optimization of wastewater treatment. The geo-referenced model GREAT-ER (Geography-referenced Regional Exposure Assessment Tool for European Rivers) has been designed to calculate spatially resolved averaged concentrations for different flow conditions (e.g. mean or low flow) based on emission estimations for local point source emissions such as treated effluents from wastewater treatment plants. The methodology was applied to selected pharmaceuticals (diclofenac, sotalol, metoprolol, carbamazepin) in the Main river basin in Germany (approx. 27,290 km²). Average concentrations of the compounds were calculated for each river reach in the whole catchment. Simulation results were evaluated by comparison with available data from orienting monitoring and used to develop an optimal monitoring strategy for the assessment of water quality regarding micropollutants at the catchment scale.