Large White Female Pigs Research Articles

Intramyocardial immunomodulation with human CD16+ monocytes to treat myocardial infarction in pig: a blind randomized preclinical trial.

Human CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI). A total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; -55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; -30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-β were observed in the hCD16+ Ms group. The use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-β at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.

Evaluation of lingual oscillometric blood pressure measurement in anaesthetized pigs

ObjectiveTo evaluate the agreement between measurements of invasive blood pressure (IBP) and oscillometric blood pressure from the tongue (OBPton) using a multiparameter monitor. Study designUnblinded, prospective, experimental study. AnimalsA total of 12 female Large White crossbreed pigs. MethodsPigs undergoing experimental procedures that required arterial cannula placement were recruited. A blood pressure cuff with the closest width to 40% of the circumference of the tongue was placed rostral to the lingual frenulum. Systolic, mean and diastolic IBP and OBPton were measured simultaneously at 5 minute intervals. Agreement between paired measurements was examined using Bland–Altman analysis. Mean bias, precision (standard deviation of mean bias), 95% limits of agreement, correlation coefficients and percentage of measurements within 10 and 20 mmHg of IBP were calculated. ResultsThe total numbers of paired measurements recorded were 124, 126 and 124 for systolic, mean and diastolic blood pressures, respectively. The mean bias, precision and 95% limits of agreement for systolic OBPton were 11.5, 11.5 (–11.1 to 34.2), for mean OBPton 5.6, 5.7 (–5.7 to 16.8) and for diastolic OBPton 7.6, 10.1 (–12.1 to 27.4) mmHg. Correlation coefficients were greater than 0.9 for mean OBPton only. More than 50% of measurements were within 10 mmHg of IBP and 80% of measurements were within 20 mmHg of IBP for mean and diastolic OBPton only. Conclusions and clinical relevanceThe tongue as a cuff site for oscillometric blood pressure measurement is a useful site for measuring mean arterial, but not systolic or diastolic blood pressure in anaesthetized Large White crossbreed pigs. This technique fulfils the American College of Veterinary Internal Medicine criteria for measuring mean arterial pressure but not systolic or diastolic arterial pressure.

Pharmacokinetics of chelerythrine and its metabolite after oral and intramuscular administrations in pigs

The objective of this study was to investigate the single- and multiple-dose pharmacokinetics of chelerythrine (CHE) and its metabolite, dihydrochelerythrine (DHCHE), after oral and IM administrations in pigs. Six crossbreed (Landrace × Large White) female pigs (7–8 weeks old; 24.1 ± 2.6 kg bw) administered oral and IM CHE at a dose of 0.1 mg/kg orally and intramuscularly in a cross-over design. Multiple oral administration was performed at 0.1 mg/kg a time, three times a day at 8-h intervals for three consecutive days. Blood samples were collected from the anterior vena cava and placed into heparinized centrifuge tubes before dosing (time 0 h) and at different times after oral and IM administrations. Pre-treatment plasma was analysed by high-performance liquid chromatography-tandem mass spectrometry. After IM administration, CHE and DHCHE rapidly reached peak concentrations (Cmax , 69.79 ± 15.41 and 3.47 ± 1.23 ng/mL) at 0.42 ± 0.13 and 0.33 ± 0.13 h, respectively. After single oral administration, CHE and DHCHE rapidly increased to reach Cmax of 5.04 ± 1.00 and 1.21 ± 0.35 ng/mL at 1.83 ± 0.26 and 1.67 ± 0.26 h, respectively. The half-life (T 1/2) was 2.03 ± 0.26 and 2.56 ± 1.00 h for CHE and DHCHE, respectively. After multiple oral administration, the average steady-state concentrations (Css ) of CHE and DHCHE were 2.51 ± 0.40 and 0.6 ± 0.06 ng/mL, respectively. CHE is metabolized rapidly after a single oral administration, multiple daily doses and long-term use of CHE are recommended.

Abdominal aortic aneurysm model in swine with bovine pericardium patch.

BackgroundAneurysm repair using endovascular techniques has grown in importance as materials have improved. Studies of endovascular prostheses require experimental models that reproduce anatomic and pathophysiological characteristics of human aneurysms.ObjectivesTo describe a porcine model of abdominal aortic aneurysm.MethodsThis prospective cohort study used eleven Large White female pigs with a mean age of 12 weeks in two study phases. In phase I, the aneurysm was produced with a bovine pericardium patch by retroperitoneal surgery conducted under general anesthesia. In phase II, 15 days later, the animals underwent arteriography and were then euthanized before specimens were removed for histological analysis.ResultsFormation of parietal thrombus was observed in all animals. Microscopic analysis showed calcifications around thrombus in 82% of the animals. There was lymphoplasmacytic infiltration in the graft and adjacent area, with fibrosis in nine animals. Three pigs had substantial myointimal thickening, and eight had microcalcifications. Mortality was zero, and there were no ruptures, ischemia, or surgery site infections.ConclusionsThis is a unique model, using inexpensive, biocompatible material. Bovine pericardium is easy for the surgeon to handle and has very similar characteristics to autologous tissue in terms of integration with the cell wall.

Drone brood fed supplement impacts on the folliculogenesis in growing gilts

The biological properties of bee drone brood make it an ideal additive for growth promotion in animal husbandry instead of banned hormonal anabolics and antibiotics. However, the drone brood action on mammalian ovaries has not been well studied. The present study analyzes the impact of drone brood homogenate (DBH) in the diet of growing gilts on folliculogenesis. Large White female pigs at the age of 35 days were randomly divided into two groups of 10 animals each, and fed with the same basal diets. The experimental group was supplemented with 25 mg/kg forage of DBH for 180 days, after which the animals were slaughtered and morphometric, histological and immunohistochemical evaluation of their ovaries was performed. In addition, the expression of ovarian growth factors BMP15 and GDF9 in oocytes and cumulus cells was analyzed by RT-PCR. A significant increase in body weight and average daily gain at day 145 in the DBH-supplemented group was established. The length of the ovaries in the treated animals also was enhanced. More pools of primordial follicles, involved in intensive growth, as well as a larger diameter of primary and tertiary follicles were found in the ovaries of DBH-supplemented animals. These findings corresponded with an increase in the expression of GDF9 mRNA in the oocytes and cumulus cells. At the same time, signs of atresia in the Graafian follicles of treated animals were observed. The supplementation with DBH stimulates the early stages of folliculogenesis in gilts, but provokes atresia in the last stage of follicular development.

Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194). A dose range of 5-25mg would be tested, starting with 10mg in cohort 1. No significant difference between Mirococept at 10mg and control was detected; hence the study was stopped to enable a further dose saturation study in a porcine kidney model. The optimal dose of Mirococept in pig kidney was 80mg. This dose did not induce any additional histological damage compared to controls or after a subsequent 3hours of normothermic machine perfusion. The amount of unbound Mirococept postperfusion was found to be within the systemic dose range considered safe in the Phase I trial. The ex vivo administration of Mirococept is a safe and feasible approach to treat DGF in deceased donor kidney transplantation. The porcine kidney study identified an optimal dose of 80mg (equivalent to 120mg in human kidney) that provides a basis for further clinical development.

P565First characterization of high-power short-duration radiofrequency ablation with remote magnetic navigation assistance

Abstract Funding Acknowledgements MEYS- CR (ref#LQ1605 and LM2015062) Background/Introduction High-power short-duration (HPSD) radiofrequency (RF) ablation relies on the application of intense thermal fields for a carefully restricted time, in order to quickly obtain deep but precise lesions that spare the structures surrounding the heart. The approach is still under evaluation across different therapies and catheter technologies. To the present day there is no available characterization of HPSD ablation supported by remote magnetic navigation (RMN). Purpose To describe the safety issues regarding HPSD ablation in atria and ventricles with RMN systems, while characterizing the thermal lesion size and continuity in an acute closed-chest swine model. Methods The animal trial was divided in two arms (left ventricular and atrial). 10 female large white pigs (6-month-old weight 55-65 kg) were employed in each arm. Endocardial electroanatomical mapping and ablation were performed with RMN assistance to provide stable contact and flexible maneuvering. The ventricular cohort was divided in 5 power settings (30-40-50-60-70W). Multiple RF applications (10 ca./animal) were delivered until a pop occurred or up to 60s. In the atrial cohort the animals were divided by a combination of power/application time (50W/20s – 70W/10s – 90W/4s). Intracaval right atrial ablation lines and postero-lateral left atrial lines were performed in a point-by-point fashion (ca. 4mm distance). Irrigation rate was 30ml/min. The ventricular lesions were measured via software after 9.4T MRI of fixed hearts. The atrial lesions were measures during pathological examination after explanation. Results In the ventricular arm, we obtained a safety calibration curve linking the imposed power setting to the maximal time of application. The time before a pop decreased non-linearly from 60s down to 17.69 ± 8.21 s at 70W. No statistically significant differences were observed when comparing lesions depth, width and volume among the selected power settings. In the atrial arm we observed on the post-ablation maps a significant decrease of intracaval lesions (i.e. area with bipolar voltage <1.5mV) width (17.57 ± 1.89 mm for 50W/4s down to 10.16 ± 1.56 mm for 90W/4s). Pericardial, pleural and aortic damages were visible across all the employed settings, with less pronounced alterations for 90W/4s. Transmural lesions were visible both on the right and left atrium, with evident gaps for 50W/20s. Conclusion The presented work assesses for the first time the safety limits of HPSD ablation on healthy ventricular myocardium. We provide a calibration curve for faster RF ablation with comparable lesion features. Furthermore, we expanded the previously reported application in the atrium adding the benefits of stable controlled contact provided by RMN systems. We highlighted the benefits (e.g. faster, continuous and localized lesion formation) and risks for peripheral structures using HPSD ablation for supraventricular tachycardia interventions. Abstract Figure.

Bipolar ablation with contact force‐sensing of swine ventricles shows improved acute lesion features compared to sequential unipolar ablation

Despite technical progress, ventricular tachycardia (VT) recurrence after unipolar ablation remains relatively high (12%-47%). Bipolar ablation has been proposed as an appealing solution that may overcome limitations associated with unipolar ablation settings. We designed an animal study to compare bipolar (BPA) vs sequential unipolar ablation (UPA) using contact force-sensing technology on both ablation catheters. Twenty large white female pigs (6-months-old, 50-60 kg) underwent multiple RF ablations (30 W, 60 seconds, 30 mL/min irrigation) on the ventricular myocardium from the epicardial and endocardial sides. The hearts were fixed and scanned with high-resolution cardiac magnetic resonance imaging. Thermal lesions were located and characterized in volume, depth, width, and transmurality. Lesion volume was calculated as the sum of epicardial or endocardial conjoined/isolated lesions at one location. Linear dimensions (width and depth) were measured twice for each location, on the endocardial and epicardial side. We evaluated 35 lesions across the intraventricular septum (UPA, N = 17 vs BPA, N = 18). No difference in volume, linear dimensions or impedance drop was observed in this area between UPA and BPA. However, BPA required half RF time and showed an increased transmurality trend. We then analyzed 73 lesions from the endocardial side (UPA, N = 35 vs BPA, N = 38) and 50 from the epicardial side (UPA, N = 11 vs BPA N = 39) of the ventricular free walls. Lesion transmurality was markedly improved by BPA (P = .030, odds ratio, 23.73 [4.71,31.96]). Ventricular BPA lesions were significantly deeper on the epicardial side (P < .0001) and endocardial side (P = .015). Bipolar ablation is more likely to create transmural and epicardial lesions in the ventricle wall. Half the time is needed for the creation of comparably deep and large lesions.

P5700Comparison of efficacy and safety of ventricular lesions formation by unipolar and bipolar radiofrequency ablation on an animal model

Abstract Aims Despite all this technical progress, VT recurrence after unipolar ablation remains relatively high (12–47%). Bipolar ablation has been proposed as an appealing solution, which may overcome boundaries associated with unipolar ablation settings. Therefore, we have proposed an animal study to compare bipolar (BPA) vs sequential unipolar ablation (UPA) using a contact-force sensing technology on both catheters. Methods 20 large white female pigs (6 months-old, 60–70kg) underwent multiple RF ablations (30W, 60s, 30ml/min irrigation) on ventricular myocardium, from epicardial and endocardial sides. After the procedure, the animal underwent euthanasia, cardioplegia and organ excision. The hearts were fixed and underwent high-resolution cardiac MRI. Each lesion was characterized primarily in terms of volume, depth, width and transmurality. Results We evaluated 35 lesions across the intraventricular septum. No difference in volume, linear dimensions and impedance drop was observed in this area, between the two ablation settings. However, for the generation of unipolar lesions, twice the ablation time was needed. Transmurality of the lesions shows a trend in favor of BPA. We then analyzed 73 lesions from the endocardial side and 34 from the epicardial one of the ventricular free walls. Lesion transmurality was found remarkably improved in BPA (p=0.030, OR 23.73 [4.71,11.96]). Ventricular BPA lesions were significantly deeper on the epicardial side (p&lt;0.0001) Conclusion BPA is more likely to create transmural lesions in the ventricle, when compared to UPA. Half the time is needed for the creation of comparably deep and large lesions. BPA is specifically more effective in creating epicardial lesions.

Hermetia illucens larvae as a potential dietary protein source altered the microbiota and modulated mucosal immune status in the colon of finishing pigs

BackgroundInsects, such as Hermetia illucens larvae, are rich in chitin and proteins, and represent a suitable feed ingredient replacement for animals. However, little is known about the effect of administering H. illucens larvae on intestinal microbiota, bacterial metabolite profiles, and mucosal immune status in animals. This study aimed to investigate the effects of administering H. illucens larvae on colonic microbiota and bacterial metabolites production in finishing pigs. Seventy-two crossbred (Duroc × Landrace × Large White) female pigs (initial body weight, 76.0 ± 0.52 kg) were randomly allocated to three different dietary treatments: a control diet (Control group) and two diets corresponding to 4% (H1 group) and 8% (H2 group) H. illucens larvae inclusion levels, respectively. Each treatment consisted of eight pens (replicates), with three pigs per pen. After 46 days of feeding, eight pigs per treatment (n = 8) were slaughtered, and the colonic digesta and mucosa were collected for microbial composition and microbial fermentation products, and genes expression analyses.ResultsThe results showed that the H1 diet significantly increased the abundance of Lactobacillus, Pseudobutyrivibrio, Roseburia, and Faecalibacterium compared with those in the control group (P < 0.05), with a decrease in the abundance of Streptococcus. The numbers of Lactobacillus, Roseburia, and Clostridium cluster XIVa were significantly greater in the H1 group than in the control group (P < 0.05). Meanwhile, H2 diet increased the number of Clostridium cluster XIVa compared with the control group (P < 0.05). For colonic metabolites, total short chain fatty acids, butyrate, and isobutyrate concentrations were significantly higher in the H1 group than those in the control group (P < 0.05); the H1 treatment caused a striking decrease in protein fermentation compared with the control group, as the concentrations of total amines, cadaverine, tryptamine, phenol, p-cresol, and skatole were significantly lower (P < 0.05). Additionally, H2 diet also increased butyrate concentration compared with control group (P < 0.05), while decreased the concentrations of phenol, p-cresol, and skatole (P < 0.05). Pigs in the H1 group down-regulated the expression of TLR-4 and pro-inflammatory cytokines (IFN-γ) compared with pigs in the control group (P < 0.05), and up-regulated anti-inflammatory cytokine (IL-10) and intestinal barrier genes (ZO-1, occludin, and mucin-1). H2 diet up-regulated the expression of ZO-1 compared with control group (P < 0.05). Furthermore, the changes in the colonic mucosal gene expression were associated with changes in the bacterial composition and their metabolites.ConclusionsCollectively, dietary inclusion of Hermetia illucens larvae may enhance mucosal immune homeostasis of pigs via altering bacterial composition and their metabolites. These findings provide a new perspective on insect meal as a sustainable protein source rich in nutrient ingredients for swine.

Validation of new marker of fluid responsiveness based on Doppler assessment of blood flow velocity in superior vena cava in mechanically ventilated pigs

BackgroundWe studied a novel approach for the evaluation and management of volemia: minimally invasive monitoring of respiratory blood flow variations in the superior vena cava (SVC). We performed an experiment with 10 crossbred (Landrace × large white) female pigs (Sus scrofa domestica).MethodsHypovolemia was induced by bleeding from a femoral artery, in six stages. This was followed by blood return and then an infusion of 1000 ml saline, resulting in hypervolemia. Flow in the SVC was measured by Flowire (Volcano corp., USA), located in a distal channel of a triple-lumen central venous catheter. The key parameters measured were venous return variation index (VRV)—a new index for fluid responsiveness, calculated from the maximal and minimal velocity time intervals during controlled ventilation—and systolic peak velocity (defined as peak velocity of a systolic wave using the final end-expiratory beat). A Swan–Ganz catheter (Edwards Lifesciences, USA) was introduced into the pulmonary artery to measure pulmonary arterial pressure, pulmonary capillary wedge pressure, and continuous cardiac output measurements, using the Vigilance monitor (Edwards Lifesciences, USA).ResultsWe analyzed 44 VRV index measurements during defined hemodynamic status events. The curves of VRV indexes for volume responders and volume non-responders intersected at a VRV value of 27, with 10% false negativity and 2% false positivity. We compared the accuracy of VRV and pulse pressure variations (PPV) for separation of fluid responders and fluid non-responders using receiver operating characteristic (ROC) curves. VRV was better (AUCROC 0.96) than PPV (AUCROC 0.85) for identification of fluid responders. The VRV index exhibited the highest relative change during both hypovolemia and hypervolemia, compared to standard hemodynamic measurement.ConclusionsThe VRV index provides a real-time method for continuous assessment of fluid responsiveness. It combines the advantages of echocardiography-based methods with a direct and continuous assessment of right ventricular filling during mechanical ventilation.

OneShot-M: A New Device for Close Laparoscopy Pneumoperitoneum.

The induction of pneumoperitoneum is the first and most critical phase of laparoscopy, due to the significant risk of serious vascular and visceral complications. The closed technique for the creation of pneumoperitoneum could lead to several surgical complications. The present study aimed to overcome the complications associated with the insertion of Veress needle, improving its use, and facilitating the rapid creation of pneumoperitoneum. Thirty large white female pigs were enrolled in our study. A common plunger was modified in order to allow the passage of a 15-cm long Veress needle. This method was applied to 26 laparoscopic procedures (26 pigs) of several specialist branches. OneShot-M close laparoscopy pneumoperitoneum creation device allowed us to obtain pneumoperitoneum quickly in all attempts, without any intraoperative and postoperative complications related to the use of the Veress needle. The use of the proposed device showed an induction time as quick as the standard laparoscopic closed abdominal entry. The patented device is cheap and allows a safe abdominal entry. In addition, abdominal entry is much faster than the classic open technique.

Outcomes of Kidney Transplantation by Laparoscopic Surgery versus Open Surgery

Introduction Laparoscopic surgery for live donor nephrectomy has become the standard of care due to multiple benefits. This has also facilitated an increase in the live donor pool. Over last few years, laparoscopic surgery for kidney transplantation has been explored with promising results. However, concerns have been raised as to whether there is any additional predisposition to damage to the kidney graft due to prolonged time for vessel anastomosis during learning period. Therefore, the aims of this study are to investigate the outcomes of kidney transplantation by laparoscopic surgery in comparison with open surgery in a large animal model. Materials and Methods The study was approved by the Animal Ethics Committee of the institute. Eleven large white female pigs, weighing about 40 kg were selected for this study. The model of orthotopic auto transplantation was employed in this study with transplantation performed by laparoscopic surgery in six pigs (LG), and open surgery in five pigs (OG). The technique of laparoscopic kidney transplantation has been described previously with 5 ports and a small ventral midline incision (6-8 cm). The open surgery was performed by a large flank incision about 18 cm in length. The pigs recovered from surgery and were monitored for 4 weeks. Body temperature was monitoredKidney graft temperature was monitored during vessel anastomosis. A kidney biopsy was taken prior to kidney procurement and kidney implantation, immediately post implantation and at the end of study. The time for vessel anastomoses was recordedBlood tests of haemoglobin (Hb) and creatinine (Cr) were done for assessment of the kidney function. Outcomes All surgeries were performed successfully. The recovery in 7 pigs was uneventful, while 2 pigs in each group required early euthanasia during the recovery period. The venous anastomotic time was similar in both groups, although the renal artery anastomosis was longer in LG (P<0.05). Body temperature was stable during the surgery.Kidney temperature rapidly increased to ~20°C and then slowly increased until completion of vessel anastomosis.The Hb level was stable pre and post surgery in both groups. The peak Cr level was on day 1 and returned to pre-operative levels by day 7. The Cr level was significantly higher in OG on day 1 and day 3 post-transplant, then returned close to normal level from day 7 and remained stable until the end of study. Histopathology of the biopsy was similar in both groups with very mild change. The incision was significantly smaller in LG than OG Conclusion The recovery of kidney graft function after transplantation was comparable between the two groups.The Kidney graft temperature increased rapidly, then remained steady.There is no specific damage seen on histopathology in the kidney graft that was transplanted by laparoscopic surgery. The major advantage of laparoscopic surgery over open surgery is a minimally invasive with a smaller incision.

Proposal of a New Electrode and Modality of Electrical Stimulation for Diaphragmatic Pacemakers

This report describes the implantation of a new design of intramuscular electrode to the diaphragm and introduces a new modality of electroventilation for diaphragmatic pacemaker. We used 22 Large White female pigs to test 68 electrodes that were implanted in the abdominal portion of the diaphragm by videolaparoscopy. Animals were submitted to a new protocol of electroventilation with an unpolarized current and a single-channel mode with 1 electrode for each hemidiaphragm during 3 hours. The electrodes were easily fixed to the diaphragm with the help of a deployment device designed for this purpose. There was no evidence of clinical complications such as pneumothorax or bleeding. No significant differences were observed in arterial blood gas analysis and serum lactate levels. The designed electrodes provided an excellent performance in connection between the electrical stimulator and the muscle tissue. The proposal for using an unpolarized current proved to be effective in stimulating both hemidiaphragms simultaneously with only a single channel of the electrical stimulator.

An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver Transplantation.

Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted. All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.

The increased expression of follicle-stimulating hormone leads to a decrease of fecundity in transgenic Large White female pigs.

Follicle-stimulating hormone (FSH) is a pituitary gonadotropin regulating reproduction in mammals. Overexpression of the exogenous FSHα/β genes from Chinese Erhualian pigs improved female fecundity of transgenic (TG) mice and male spermatogenesis ability of Large White TG boars. Here, we investigated the impact of the exogenous FSHα/β genes on female reproductive performance of Large White TG pigs. First, we identified the integration site of the exogenous FSHα/β genes at 140,646,456bp on chromosome 9 in these TG pigs using whole-genome sequencing. Then, we showed that TG gilts had higher levels of serum FSH and FSHβ protein in pituitary while had a potentially lower number of born piglets than their wild-type half sibs. TG gilts grew healthily and normally without significant difference in growth and health parameters as compared to WT gilts. The expression levels of FSHR, LHR, ESR1 and ESR2 were significantly lower in TG gilts than in WT gilts at the age of 300days. Taken together, we proposed that the overexpressed FSHα/β transgenes could cause deteriorate fecundity via disturbing the normal expression of the endogenous reproduction-related genes in female pigs. Our findings provide insight into the effect of overexpression of FSHα/β on female reproduction performance in pigs.

Feasibility of profound hypothermia as part of extracorporeal life support in a pig model

ObjectiveTo investigate the feasibility of a refined aortic flush catheter and pump system to induce emergency preservation and resuscitation before extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest swine model simulating near real size/weight conditions of adults. MethodsIn this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4°C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a new hardware ensued by resuscitation with extracorporeal cardiopulmonary resuscitation. ResultsBrain temperature was lowered from 39.9°C (interquartile range [IQR] 39.6-40.3) to 24.0°C (IQR 20.8-28.9) in 12 minutes (IQR 11-16) with a median cooling rate of 1.3°C (IQR 0.7-1.6) per minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure of 1487 mm Hg (IQR 1324-1545) were pumped to the brain. ConclusionsWith the new hardware, we were able to cool the brain within a few minutes in a large pig cardiac arrest model. The exact position; the design, diameter, and length of the flush catheter; and the brain perfusion pressure seem to be critical to effectively reduce brain temperature. Redistribution of peripheral blood could lead to sterile inflammation again and might be avoided.

Comparing Non-Linear Models to Describe the Growth Performance in Large White Yorkshire Pigs

An attempt was made to apply different nonlinear growth models to predict the best growth model for Large White Yorkshire pigs and to examine the difference in the growth pattern of male and female piglets.The data pertaining to achieve the objectives were collected between 2011 to 2016 at PGRIAS,Kattupakkam,on bodyweights at different ages of pigs with the sample size of 1226 Male and 1120 Female Large White Yorkshire pigs were included in the study. The data on body weights were plotted against the age for both males and females separately,and the shape of the curve was examined. Based on the shape of the curves,the following models were fitted to the data,viz.,Brody model, Logistic model, Gompertz model,Von Bertalanffy model,and Richard model. For non linear models,the hightest R square value,Root Mean Square Error(RMSE), Mean Absolute Error (MAE), and Mean Absolute Predicted Error (MAPE) criteria were used to determine the best fitted model. The analysis of data revealed that in male pigs the value of highest R2 (0.999)and least MAE (0.597), RMSE(1.755), MAPE(29.85) were observed in Gompertz model followed by Logistic model, Incase of female pigs the highest R2 (0.998) and least MAE (0.654), RMSE(1.130), MAPE(29.03) were seen for Gompertz model.Thus,it could be concluded that as the best fit for assessing growth of male and female Large White Yorkshire pigs.

More tail lesions among undocked than tail docked pigs in a conventional herd

The vast majority of piglets reared in the European Union (EU) and worldwide is tail docked to reduce the risk of being tail bitten, even though EU animal welfare legislation bans routine tail docking. Many conventional herds experience low levels of tail biting among tail docked pigs, however it is not known, what the prevalence would have been had the pigs not been tail docked. The aim of this study was to compare the prevalence of tail lesions between docked and undocked pigs in a conventional piggery in Denmark with very low prevalence of tail biting among tail docked pigs. The study included 1922 DanAvl Duroc×(Landrace×Large White) female and castrated male pigs (962 docked and 960 undocked). Docked and undocked pigs were housed under the same conditions in the same room but in separate pens with 20 (±0.03) pigs/pen. Pigs had ad libitum access to commercial diets in a feed dispenser. Manipulable material in the form of chopped straw was provided daily on the floor (~10 g/pig per day), and each pen had two vertically placed soft wood boards. From weaning to slaughter, tail wounds (injury severity and freshness) were scored every 2nd week. No clinical signs of injured tails were observed within the tail docked group, whereas 23.0% of the undocked pigs got a tail lesion. On average, 4.0% of the pigs with undocked tails had a tail lesion on tail inspection days. More pens with tail lesions were observed among pigs weighing 30 to 60 kg (34.3%; P<0.05) than in pens with pigs weighing 7 to 30 kg (13.0%) and 60 to 90 kg (12.8%). Removal of pigs to a hospital pen was more likely in undocked pens (P<0.05, 47.7% undocked pens and 22.9% docked pens). Finally, abattoir meat inspection data revealed more tail biting remarks in undocked pigs (P<0.001). In conclusion, this study suggests that housing pigs with intact tails in conventional herds with very low prevalence of tail biting among tail docked pigs, will increase the prevalence of pigs with tail lesions considerably, and pig producers will need more hospital pens. Abattoir data indicate that tail biting remarks from meat inspection data severely underestimate on-farm prevalence of tail lesions.

Usefulness of thermographic analysis to control temperature homogeneity in the development and implementation of a closed recirculating CO2 chemohyperthermia model

Purpose: To determine the effectiveness of thermography to control the distribution of abdominal temperature in the development of a closed chemohyperthermia model.Materials and methods: For thermographic analysis, we divided the abdominopelvic cavity into nine regions according to a modification of carcinomatosis peritoneal index. A difference of 2.5 °C between and within the quadrants, and thermographic colours, were used as asymmetric criteria. Preclinical study:· Rats Model: Six athymic nude rats, male, rnu/rnu. They were treated with closed technique and open technique. Porcine Model: 12 female large white pigs. Four were treated with open technique and eight with closed recirculation CO2 technique. Clinical Pilot Study, EUDRACT 2011-006319-69: 18 patients with ovarian cancer were treated with cytoreductive surgery and hyperthermia intraperitoneal chemotherapy, HIPEC, with a closed recirculating CO2 system. Thermographic control and intra-abdominal temperature assessment was performed at the baseline, when outflow temperature reached 41 °C, and at 30´.Results: The thermographic images showed a higher homogeneity of the intra-abdominal temperature in the closed model respect to the open technique. The thermogram showed a temperature distribution homogeneity when starting the circulation of chemotherapy. There was correlation between the temperature thermographic map in the closed porcine model and pilot study, and reached inflow and outflow temperatures, at half time of HIPEC, of 42/41.4 °C and 42 ± 0.2/41 ± 0.8 °C, respectively. There was no significant impact to the core temperature of patients after reaching the homogeneous temperature distribution.Conclusions: To control homogeneity of temperature distribution is feasible using infra-red digital images in a closed HIPEC with CO2 recirculation.