Porcine Animal Model Research Articles

Characterising okadaic acid (OA) toxicity both in vitro and in vivo, using a comparative porcine model (MOKAPIG).

Food toxicology helps to protect the health and safety of consumers by a better understanding of the impact of xenobiotics and natural toxins on public health. Professors Mauro Dacasto (UNIPD), Flavia Girolami (UNITU), and Anna Zaghini (UNIBO) have collaborated on a research assessing the impact of aflatoxin B1 (a harmful mycotoxin) on bovine and human health. In their current project, MOKAPIG, the researchers are using comparative human and pig in vitro models as well as the weaned pig as an animal model to shed a light on the fate of differing levels of okadaic acid (OA) in target tissues such as the gastrointestinal tract and the liver. The goal of the two-year project is to expand the existing knowledge on the effects of OA on humans and pigs, including data on OA toxicokinetics, toxicodynamics and mechanistic toxicology. This will help to improve the protection of consumer health and seafood safety. MOKAPIG will first assess OA cytotoxicity and its bioavailability in vitro, characterise and profile OA metabolism and carry out comparative toxicogenomic studies. Then, the project will explore the in vivo toxicity of OA using a porcine animal model. The reasoning behind selecting a porcine over a rodent model is that mice show limitations for the assessment of marine toxins comparative toxicity, e.g, species-differences in xenobiotic metabolism.

Thyroid Radiofrequency Ablation-Thermal Effects on Recurrent Laryngeal Nerve Using Continuous Intraoperative Neuromonitoring Animal Model.

When performing radiofrequency ablation for thyroid nodules, it is essential to avoid thermal injury to the recurrent laryngeal nerve. This porcine animal model study used continuous intraoperative neuromonitoring to investigate the thermal safety parameters of thyroid radiofrequency ablation. Porcine animal study. University animal laboratory. Twelve piglets were tested at different radiofrequency power levels, and the real-time electromyography signal changes were recorded under continuous intraoperative neuromonitoring. The spread heat study (8 piglets) included spontaneous recovery tests and cold water irrigation tests to investigate the safety distance from the recurrent laryngeal nerve to the active tip during 5-second activation with standard stimulation patterns. The residual heat study (4 piglets) investigated the safety cooling durations by touching the recurrent laryngeal nerve with the tip after a 5-second activation. In the spread heat study, substantial signal attenuation events were observed at an spread heat distance of 2, 3, 5, and 5 mm when the power was set as 10, 20, 30, and 50 W, respectively. No signal recovery could be observed in 20 minutes with or without cold water irrigation in the injured recurrent laryngeal nerve area. The residual heat study shows the residual thermal effect of the tip is minimal, and no substantial signal attenuation event was observed at all experiments. This innovative study established the thermal safety parameters for radiofrequency ablation in a porcine model at various power levels, which can potentially assist operators in delineating a precise ablation field and providing effective thyroid ablation treatment safely.

Imaging of ventilation and lung injury with low-frequency tomographic ultrasound.

Mechanical ventilation in the intensive care unit (ICU) is a life-saving technique for patients with acute respiratory failure, but is also associated with a high incidence of complications in the injured lung. Currently, there is no widely used monitoring technique to guide the ventilator setting to facilitate a precision medicine approach or to provide a real-time alert for developing adverse pulmonary conditions. Conventional ultrasound has been used as a thoracic bedside technology, but the lack of signal penetration into lung tissue results in images that often contain more information in their artifacts than in the images themselves. Perhaps the greatest obstacle to using traditional ultrasound in the ICU is the need for highly skilled technicians to perform the data collection. In contrast, low-frequency ultrasound (50-500 kHz) has been shown to penetrate the lung, and can detect air trapping in patients with chronic obstructive pulmonary disease (COPD). Here, we present a method of collecting low-frequency ultrasound computed tomographic (USCT) data in vivo on a mechanically ventilated porcine model and computing tomographic reconstructions of airflow during tidal breathing and induced lung injuries. We evaluate the ability of the novel low-frequency USCT system to image regional changes in sound speed in the thorax due to changes in airflow during tidal breathing and induced lung injuries. This represents the first study of low-frequency tomographic ultrasound imaging in vivo and the first to produce tomographic images of ventilatory changes invivo. USCT and computed tomography (CT) scan data were collected alternately on a mechanically ventilated Landrace pig weighing approximately 75 kg during tidal breathing, induced pneumothorax, atelectasis, and pleural effusion. The pneumothorax was induced by injecting air through a 5 mm thick intrathoracic tube inserted in the 8th posterior intercostal space. After removing the air, atelectasis was induced by ventilating the animal with a high concentration of oxygen and low tidal volumes. The pleural effusion was induced by injecting a saline solution through the tube. The USCT data were collected at 125 kHz using the USCT low-frequency ultrasound tomography (LUFT) system on a transducer belt placed around the animal's thorax. Tomographic reconstructions were computed from the USCT data using a regularized refraction-corrected Gauss-Newton-based time-of-flight reconstructionalgorithm. Cyclic changes in computed lung area during tidal breathing were demonstrated to agree with the respiratory rate on the mechanical ventilator. Reconstructed images computed at time steps during the procedure demonstrate regional changes consistent with what would be expected during the induced lung injury. No ground truth was available for images during the procedures since CT scans could only be taken before and after each established lunginjury. In this work, we have demonstrated in the first in vivo study using a mechanically ventilated porcine animal model that low-frequency ultrasound tomography has the ability to image regional changes in sound speed in the thorax corresponding to changes in airflow during tidal breathing and induced lung injury. The results show promise for using low-frequency USCT as a bedside imaging technique in the future for patients with acute respiratory distresssyndrome.

Changes in heart dimensions in decomposition using porcine and ovine animal models: a method for estimating decomposed human heart weight

ABSTRACT Heart weight is a routine measurement at post-mortem examination. An increased heart weight is associated with pre-existing heart disease and sudden cardiac death. However, during decomposition, the heart weight measured at post-mortem examination may not reflect the weight at the time of death. A previous study showed that heart dimensions can be used to estimate heart weight. This study documents the changes in heart dimensions during decomposition using porcine and ovine animal models. It shows that, in contrast to heart weight, which decreases in the post-mortem interval, the heart dimensions increase. Heart width increases and subsequently plateaus at the end of the 18 days to a mean of 6 and 8 mm in ovine and porcine hearts, whereas the length continues to increase. Using the results of this study, in conjunction with previous published literature, the heart width may be used as a parameter to estimate heart weight and determine cardiac hypertrophy at the time of death in decomposed hearts.

Biocompatible Liquid Embolic for the Treatment of Microvascular Hemorrhage.

Persistent or recurrent bleeding from microvessels inaccessible for direct endovascular intervention is a major problem in medicine today. Here, an innovative catheter-directed liquid embolic (P-LE) is bioengineered for rapid microvessel embolization to treat small vessel hemorrhage. Tested in rodent, porcine, and canine animal models under normal and coagulopathic conditions, P-LE outperformed clinically used embolic materials in both survival and non-survival experiments, effectively occluding vessels as small as 40 microns with no signs of recanalization. P-LE occlusion is independent of the coagulation cascade, and its resistance to displacement is ≈ 8 times greater than systolic blood pressure. P-LE is also found to be biocompatible and x-ray visible and does not require polymerization or a chemical reaction to embolize. To simulate the clinical scenario, acute microvascular hemorrhage is created in the pig kidney, liver, or stomach; these are successfully treated with P-LE achieving immediate hemostasis. Furthermore, P-LE is found to be bactericidal to highly resistant patient-derived bacteria, suggesting that P-LE may also protect against infectious complications that may occur following embolization procedures. P-LE is safe, easy to use, and effective in treating -microvessel hemorrhage.

Toward the Clinical Translation of Safe Intravenous Long Circulating Iodinated Lipid Nanoemulsion Contrast Agents for CT Imaging.

Current clinical small molecule x-ray CT agents are effective but pose risks such as nephrotoxicity, short blood circulation time, limiting scan durations, potential thyroid impact, and immune responses. These challenges drive the development of kidney-safe x-ray nanoparticle (NP)-based contrast agents (CAs), though translation to clinical practice is hindered by chemical complexities and potential toxicity. We have engineered an intravenous, injectable, and safe blood pool NP-based CT CAs at a clinical-equivalent dose of ∼300 mgI/kg (∼2 mL/kg), ideal for vascular and hepatic imaging which are limited by clinical agents. Our iodinated lipid nanodroplet emulsions (ILNEs) contrast agent offers high x-ray attenuation thus improved contrast enhancement, extended stability, and exceptional batch-to-batch consistency. It also boasts a straightforward and scalable manufacturing process with minimal protein interaction, prolonged blood residency (∼4h), and hepatic clearance within 3 days, avoiding nephrotoxicity. Studies in vitro, in mice, and 16.6kg porcine animal model studies confirm its safety, cytocompatibility, and absence of tissue damage. Blood, and thyroid-stimulating hormone (TSH) analyses, and kidney and liver function tests, also support further toxicity evaluations for clinical translation.

Transcoronary guidewire ablation with radiofrequency in a porcine animal model.

Transcoronary ablation of septal hypertrophy (TASH) and surgical myectomy are the recommended treatment options for patients with hypertrophic obstructive cardiomyopathy refractory (HOCM) when conventional drug treatment is not sufficient. We describe the application of radiofrequency (RF) energy via coronary guidewires in an animal model for selective occlusion of coronary side branches that mimics the principle of TASH. Transcoronary guidewire ablation of coronary vessels was performed in 5 adult pigs under general anaesthesia in an animal cathlab after successful bench testing of the ablation settings. After assessing transcoronary pacing parameters, RF energy was delivered via coronary guidewires insulated by coating or by a monorail balloon and positioned in different coronary side branches. Occlusion or patency of the specific coronary side branch was documented by coronary angiography after RF delivery. After the transcoronary RF ablation, the intended occlusion of the coronary vessel (thrombolysis in myocardial infarction [TIMI]-0 or TIMI-1 flow) could be verified by angiography in 82% of the septal branches attempted and 79% of the epicardial branches. The mean ablation duration was 10.3 seconds at 20-W power with an initial impedance of 176 ± 31 Ώ. No unintended occlusion of the main vessels occurred in any case. RF ablation via coronary guidewires is a feasible method for inducing an acute occlusion of coronary vessels and may change the interventional therapy of HOCM if the current limitations of this technique are overcome.

Evaluation of a novel intramuscular prime/intranasal boost vaccination strategy against influenza in the pig model.

Live-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1-126)-ΔPAX). This virus showed a blunted replication and elicited a strong innate immune response. In the present study, we evaluated the efficacy of this vaccine candidate in the porcine animal model as a pertinent in vivo system. Immunization of pigs via the nasal route with the novel NS1(1-126)-ΔPAX LAIV did not cause disease and elicited a strong mucosal immune response that completely blocked replication of the homologous challenge virus in the respiratory tract. However, we observed prolonged shedding of our vaccine candidate from the upper respiratory tract. To improve LAIV safety, we developed a novel prime/boost vaccination strategy combining primary intramuscular immunization with a haemagglutinin-encoding propagation-defective vesicular stomatitis virus (VSV) replicon, followed by a secondary immunization with the NS1(1-126)-ΔPAX LAIV via the nasal route. This two-step immunization procedure significantly reduced LAIV shedding, increased the production of specific serum IgG, neutralizing antibodies, and Th1 memory cells, and resulted in sterilizing immunity against homologous virus challenge. In conclusion, our novel intramuscular prime/intranasal boost regimen interferes with virus shedding and transmission, a feature that will help combat influenza epidemics and pandemics.

Wet‐Printed Stretchable and Strain‐Insensitive Conducting Polymer Electrodes: Facilitating In Vivo Gastric Slow Wave Mapping

AbstractWearable and implantable devices play a crucial role in clinical diagnosis, disease treatment, and fundamental research on the body's electrophysiology and biochemical processes. Conducting polymers are emerging as promising solutions to surpass the limitations of traditional metal‐based electrodes, offering enhanced conformability, and stretchability. However, current microfabrication techniques of CP electrodes have a number of limitations. In this study, a novel wet‐printing technique is developed for the fabrication of highly stretchable poly(3,4‐ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) microelectrodes. The wet‐printing, conducted in a liquid coagulation bath, has the advantages of being non‐contact, easy and fast to perform, and capable of printing low‐viscosity inks. Wet‐printing of PEDOT:PSS lines with a width of ≈20 µm is demonstrated. By adding D‐sorbitol as a plasticizer, an ultra‐high stretchability of PEDOT:PSS electrodes, of more than 720% is achieved while the electrodes remained conductive and strain‐insensitive up to high strains. The use of PEDOT:PSS wet‐printed electrode arrays for the electrophysiological recording from the stomach is demonstrated. The stretchable electrodes conformed swell to the tissue and recorded comparable electrophysiological signals to Au‐plated electrodes in porcine and rodent animal models. The wet‐printing approach to fabricating flexible and stretchable electrode arrays using low‐viscosity, conducting inks holds promise for applications in conformable electronics.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation

Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs’ blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

An Innovative Plate Concept for Rotational Guided Growth: A Porcine Pilot Study.

Background Rotational deformities in children are currently treated with an osteotomy, acute de-rotation, and surgical fixation. Meanwhile, guided growth is now the gold standard in pediatric coronal deformity correction. This study aimed to evaluate the feasibility of a novel implant intended for rotational guided growth (RotOs Plate) in a large porcine animal model. Methodology A submuscular plate was inserted on the medial and lateral aspect of the distal femoral physis of the left femur in 6 pigs. Each plate was anchored with a screw in the metaphysis and epiphysis respectively. The plates were expected to rotate the femur externally. The right femur acted as a control in a paired design. The animals were housed for 12 weeks after surgery. MRI scanning of both femora was performed before euthanasia after 12 weeks. Rotation was determined as the difference in the femoral version on MRI between the operated and non-operated femur after 12 weeks. Results External rotation in all operated femurs was observed. The mean difference in the femoral version on MRI between operated and non-operated femurs was 12.5° (range 9°-16°). No significant changes in axial growth were detected. Conclusions This study shows encouraging results regarding rotational guided growth, which may replace current invasive surgical treatment options for malrotation in children. However, further studies addressing potential secondary deformities are paramount and should be carried out.

Safety and Efficacy of IL-12 Plasmid DNA Transfection into Pig Skin: Supportive Data for Human Clinical Trials on Gene Therapy and Vaccination.

Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies.

Histological evaluation of monopolar and bipolar radiofrequency microneedling treatment in a porcine model.

Fractional radiofrequency microneedling (FRM) is widely used as an option for skin rejuvenation, however there is a lack of histological evidence for the various energy delivery systems available. The objective was to assess thermal denaturation of tissue and the wound healing response in monopolar mode versus bipolar mode. Histological analysis was performed to demonstrate the efficacy of automatic impedance feedback system in monopolar mode. In this study, the acute thermal effects caused by monopolar FRM treatment to the dorsal skin of pigs were assessed histologically by hematoxylin & eosin (H&E) staining. Then, one session of either monopolar or bipolar FRM was used to treat one or the other side of the pig using varying power levels and pulse widths. The acute and chronic tissue reactions were assessed using H&E, immunofluorescence, and western blot analysis at 0, 14, 30, and 90 days after treatment. The efficacy of the impedance feedback system was also monitored histologically. High-energy FRM treatment produced tissue loss and necrosis. The power level and pulse duration significantly affected the coagulation amount. Histopathology at 0, 14, 30, and 90 days showed that the skin tissue reaction was more pronounced for bipolar compared to monopolar FRM. Immunofluorescence showed the expression of TGF-β, Ki67, MMP3, and elastin increased dramatically with both modes, but were higher in the bipolar FRM treated side. The automatic impedance feedback system could effectively adjust the output energy. We found that bipolar FRM produced greater thermal effects, more collagen coagulation, and more pronounced molecular changes compared with monopolar mode in a porcine animal model.

Histological examination of skin tissue in the porcine animal model after application of a new monopolar radiofrequency.

This study aims to evaluate the safety of the radiofrequency device and its efficacy in various treatment and refrigeration modes. Four4-weekBama miniature pigs were used in this study, and four repeated treatment sites were selected on the pig's abdomen, each site consisting of 6 different treatment and cooling modes, with radiofrequency device (YouMagic; WE Medical Technology Co., Ltd.) administered every 3-5 s for a total of five treatments. The handheld infrared thermometer (HIKMICRO; Hangzhou Hikmicro Sensing Technology Co., Ltd.) was used to monitor the surface temperature of skin. Twenty minutes after the completion of treatment, a biopsy of the treatment and control area was performed on the pigs using a 4-mm biopsy punch. One-month after the treatment, samples were obtained using surgical scalpels. After that we used proper staining to estimate the therapeutic efficacy. At last, SPSS and Image J were used to proceed to the next step of analysis. During the therapy, no side effects were observed apart from mild transient erythema caused by the heating of skin temperature, staining of biopsy samples taken 20 min after treatment showed no serious damage of dermis. After 1 month of treatment, it can increase collagen I and elastin production. In addition, increases in energy setting at a standard pass number also increased the expression of collagen I. Meanwhile, we also found an increase in the thickness of the dermal layer among all treatment groups. The new monopolar radiofrequency instrument possesses excellent therapeutic safety. After 1 month of treatment, it can increase collagen I and elastin production in 2-month-old Bama miniature pigs.

First Evidence of Cutaneous Remodelling Induced by Synchronized Radiofrequency Aided by High-Intensity Facial Muscle Stimulation: Porcine Animal Model.

The quality of one's facial appearance diminishes with aging as skin and underlying soft tissues deteriorate. Connective tissue and musculofascial degeneration leads to skin laxity and wrinkles developing. To evaluate the effects of synchronized radiofrequency with high intensity facial stimulation technology on dermal collagen and elastin fibers in a porcine model. Eight sows were divided into Active (N = 6) and Control (N = 2) groups. Synchronized radiofrequency and high intensity facial stimulation were delivered to the ventrolateral abdomen. The Active group received four 20-minute treatments, once a week. Control group was untreated. Skin biopsy sample were histologically analyzed for connective tissue changes pre- and post-treatment. Data were analyzed statistically (α = 0.05). In the Active group: the collagen-occupied area at baseline was 1.12 ± 0.09 × 106 μm 2 and increased by +19.6% ( p < .001) at 1-month and by +26.3% ( p < .001) 2 months post-treatment; elastin-occupied area at baseline was 0.11 ± 0.03 × 106 μm 2 and increased by +75.9% ( p < .001) at 1-month and +110.8% ( p < .001) at 2-months follow-up. No significant changes ( p > .05) found in the Control samples. Collagen and elastin fiber content increased significantly after treatments. Connective tissue in the treatment area was denser up to 2-months post-treatment.

Comparison of two viscoelastic testing devices in a porcine model of surgery, hemorrhage and resuscitation.

Viscoelastic hemostatic assays (VHA) are integral in contemporary hemostatic resuscitation, offering insights into clot formation, firmness, and lysis for rapid diagnosis and targeted therapy. Large animal models, particularly swine, provide anatomical and physiological analogies for coagulation research. Despite the growing use of VHAs, the ClotPro® device's applicability in porcine models remains unexplored. This study investigates ClotPro® in a porcine model of abdominal surgery, severe hemorrhage, and resuscitation, comparing it with the established ROTEM® delta system. Twenty-seven healthy pigs underwent abdominal surgery, hemorrhage and resuscitation. ClotPro® and ROTEM® were used to assess viscoelastic hemostatic properties at baseline, after surgery, 60min after shock induction, 60 and 120min after resuscitation. Clotting times in extrinsically and intrinsically stimulated assays exhibited fair to moderate correlation. Clot firmness in extrinsically stimulated tests could be used interchangeably while fibrin polymerization assays revealed significant differences between the devices. Fibrin polymerization assays in ClotPro® consistently yielded higher values than ROTEM®. Furthermore, the study evaluated the ClotPro® TPA-test's applicability in porcine blood, revealing failure of lysis induction in porcine blood samples. This research contributes valuable insights into the use of ClotPro® in porcine models of hemorrhage and coagulopathy, highlighting both its applicability and limitations in comparison to ROTEM® delta. The observed differences, especially in fibrin polymerization assays, emphasize the importance of understanding device-specific characteristics when interpreting results. Due to its inapplicability, TPA-test should not be used in porcine blood to evaluate fibrinolytic potential. The study provides a foundation for future investigations into the use of different viscoelastic hemostatic assays in porcine animal models.

Characterization of the Age-Related Differences in Porcine Acetabulum and Femoral Head Articular Cartilage.

The use of porcine animal models for cartilage injury has increased recently due to their similarity with humans with regard to cartilage thickness, limited intrinsic healing of chondral defects, and joint loading biomechanics. However, variations in the mechanical and biochemical properties of porcine hip articular cartilage among various tissue ages and weightbearing (WB) regions are still unknown. This study's aim was to characterize the mechanical and biochemical properties of porcine hip articular cartilage across various ages and WB regions. Articular cartilage explants were harvested from WB and non-weightbearing (NWB) surfaces of the femoral head and acetabulum of domesticated pigs (Sus scrofa domesticus) at fetal (gestational age: 80 days), juvenile (6 months), and adult (2 years) ages. Explants underwent compressive stress-relaxation mechanical testing, biochemical analysis for total collagen and glycosaminoglycan (GAG) content, and histological staining. Juvenile animals consistently had the highest mechanical properties, with 2.2- to 7.6-time increases in relaxation modulus, 1.3- to 2.3-time increases in instantaneous modulus, and 4.1- to 14.2-time increases in viscosity compared with fetal cartilage. Mechanical properties did not significantly differ between the WB and NWB regions. Collagen content was highest in the NWB regions of the juvenile acetabulum (65.3%/dry weight [DW]) and femoral head (75.4%/DW) cartilages. GAG content was highest in the WB region of the juvenile acetabulum (23.7%/DW) and the WB region of the fetal femoral head (27.5%/DW) cartilages. Histological staining for GAG and total collagen content followed the trends from the quantitative biochemical assays. This study provides a benchmark for the development and validation of preclinical porcine models for hip cartilage pathologies.

Novel treatment system using endoscopic ultrasound-guided high-intensity focused ultrasound: A proof-of-concept study

AimHigh-intensity focused ultrasound (HIFU) is a novel minimally invasive local treatment of solid tumors. Endoscopic ultrasound-guided HIFU (EUS-HIFU) using mechanical effects would have potential benefits, including precise detection of target lesions and enhance drug delivery. The aim of this study is to develop EUS-HIFU device and to prove our concept in porcine model using a locally injected phase change nano droplet (PCND) as the sensitizer. MethodA phospholipid PCND contained volatile perfluoro-carbon liquids. The prototype HIFU apparatus comprised a small (20 × 20 mm) transducer with center frequency of 2.1 MHz, attachable to a linear EUS transducer. Under general anesthetic, a single porcine received EUS-guided injection of PCND. The HIFU transducer was placed laparotomically in the stomach, and the liver was ablated through the gastric wall. ResultsPCND was injected successfully and a distinct lesion was generated at the HIFU transducer focus only in injected areas that received HIFU exposure at 4.7 kW/cm2 at a duty cycle of 5 % (mean temporal intensity, 0.245 kW/cm2) for 30 s. The generated lesions were mechanically fractionated in macroscopic view. ConclusionThe concept of transluminal HIFU ablation using novel EUS-HIFU system was proved in a porcine animal model. This novel treatment system has great potential for future cancer treatment although further investigation in more animals and different organs are warranted.

42915 Topical application of INV-10000001, a first-in-class HSP47 inhibitor, attenuates hypertrophic scar in porcine and rodent animal models

42915 Topical application of INV-10000001, a first-in-class HSP47 inhibitor, attenuates hypertrophic scar in porcine and rodent animal models

Endoscopic mucosal resection and endoscopic submucosal dissection with an external additional working channel (EMR+ and ESD+) are equivalent to using a double-channel endoscope: a systematic evaluation in a porcine ex vivo model.

With an external additional working channel (AWC) endoscopic mucosal resection (EMR) as well as endoscopic submucosal dissection (ESD) can be extended to techniques termed "EMR+" and "ESD+." These novel techniques are systematically compared to EMR and ESD under the use of a double-channel endoscope (DC). Our trial was conducted prospectively in a pre-clinical porcine animal model (EASIE-R simulator) with standardized gastric lesions measuring 3 or 4cm. EMR+ and EMR DC showed both good results for 3cm lesions with no adverse events and an en bloc resection rate of 73.33% (EMR+) and 60.00% (EMR DC, p = 0.70). They came to their limits in 4cm lesions with muscularis damages of 20.00% (EMR+), 13.33% (EMR DC, p ≥ 0.99) and decreasing en bloc resection rates of 60.00% (EMR+) and 46.67% (EMR DC, p = 0.72). ESD+ and ESD DC were both reliable concerning en bloc resection rates (100% in all groups) and adverse events (0.00% in 3cm lesions, 12.50% muscularis damages in both ESD+ and ESD DC in 4cm lesions). Resection time was slightly shorter in all groups with the AWC compared to DC although only reaching significance in 3cm ESD lesions (p < 0.05*). With the AWC, a standard endoscope can easily be transformed to double-channel functionality. We could show that EMR+ and ESD+ are non-inferior to EMR and ESD under the use of a double-channel endoscope. Consequently, the AWC presents an affordable alternative to a double-channel endoscope for both EMR and ESD.