Eradication of Staphylococcus aureus in Implant-Associated Osteomyelitis by an Injectable in situ-Forming Depot Antibiotics Delivery System.

BACKGROUND: Bone infections from Staphylococcus aureus are notoriously difficult to treat and have high recurrence rates. Local antibiotic delivery systems hold the potential to achieve high in situ antibiotic concentrations, which are otherwise challenging to achieve via systemic administration. Existing solutions have been shown to confer suboptimal drug release and distribution. Here we present and evaluate an injectable in situ-forming depot system termed CarboCell. The CarboCell technology provides sustained and tuneable release of local high-dose antibiotics. METHODS: CarboCell formulations of levofloxacin or clindamycin with or without antimicrobial adjuvants cis-2-decenoic acid or cis-11-methyl-2-dodecenoic acid were tested in experimental rodent and porcine implant-associated osteomyelitis models. In the porcine models, debridement and treatment with CarboCell-formulated antibiotics was carried out without systemic antibiotic administration. The bacterial burden was determined by quantitative bacteriology. RESULTS: CarboCell formulations eliminated S. aureus in infected implant rat models. In the translational implant-associated pig model, surgical debridement, and injection of clindamycin-releasing CarboCell formulations resulted in pathogen-free bone tissues and implants in 9/12, and full eradication in 5/12 pigs. CONCLUSIONS: Sustained release of antimicrobial agents mediated by the CarboCell technology demonstrated promising therapeutic efficacy in challenging translational models and may be beneficial in combination with the current standard of care.

Real time organ hypoperfusion detection using Indocyanine Green in a piglet model.

BACKGROUND: Preserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons' decision-making. METHODS: In this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions. RESULTS: After manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3). CONCLUSION: Continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

Continuous organ perfusion monitoring using indocyanine green in a piglet model.

BACKGROUND: Unrecognized organ hypoperfusion may cause major postoperative complications with detrimental effects for the patient. The use of Indocyanine Green (ICG) to detect organ hypoperfusion is emerging but the optimal methodology is still uncertain. The purpose of this study was to determine the feasibility of real-time continuous quantitative perfusion assessment with Indocyanine Green (ICG) to monitor organ perfusion during minimally invasive surgery using a novel ICG dosing regimen and quantification software. METHOD: In this experimental porcine study, twelve subjects were administered a priming dose of ICG, followed by a regimen of high-frequency (1 dose per minute), low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG allowing for continuous perfusion monitoring. In each pig, one randomly assigned organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3) and spleen (n = 3)] was investigated with varying camera conditions. Video recording was performed with the 1588 AIM Stryker camera platform and subsequent quantitative analysis of the ICG signal were performed using a research version of a commercially available surgical real-time analysis software. RESULTS: Using a high-frequency, low-dose bolus ICG regimen, fluorescence visualization and quantification in abdominal organs were successful in the stomach (3/3), ascending colon (1/3), rectum (2/3), and the spleen (3/3). ICG accumulation in the tissue over time did not affect the quantification process. Considerable variation in fluorescence signal was observed between organs and between the same organ in different subjects. Of the different camera conditions investigated, the highest signal was achieved when the camera was placed 7.5 cm from the target organ. CONCLUSION: This proof-of-concept study finds that real-time continuous perfusion monitoring in different abdominal organs using ICG is feasible. However, the study also finds a large variation in fluorescence intensity between organs and between the same organ in different subjects while using a fixed weight-adjusted dosing regimen using the same camera setting and placement.

The SimSpay-Student Perceptions of a Low-Cost Build-It-Yourself Model for Novice Training of Surgical Skills in Canine Ovariohysterectomy.

Practical and ethical considerations have led to an increased use of artificial substitutes for live animals in veterinary surgical skills training. However, commercially produced models are expensive and homemade models often require full-time staff to produce enough models for training large groups of students. In the Department of Veterinary Clinical and Animal Sciences of the University of Copenhagen, a low-cost build-it-yourself model, the SimSpay, was developed for novice training of surgical skills in canine ovariohysterectomy. The model did not require the use of trained technical staff or costly, hard-to-source supplies. The SimSpay was developed and implemented in the clinical veterinary curriculum in 2013. In 2014, 54 students participated in a questionnaire study to investigate their perception of the usefulness of the SimSpay as a learning tool. On a five-point Likert-type scale, students were asked to rate their perceived levels of competence, confidence, and anatomic knowledge before and after SimSpay training. Results demonstrate a strongly significant (p<.0001) increase in all three areas after training on the SimSpay. By increasing students' perceived levels of competence, confidence, and anatomic knowledge, the low-fidelity SimSpay is a useful, low-cost learning tool for teaching ovariohysterectomy.

Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome.

Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model. Two-day-old pigs were subjected to resection of 50% of the small intestine (distal part), and the remnant intestine was exteriorized on the abdominal wall as a jejunostomy. All pigs were given total parenteral nutrition for 7 days and a single daily injection of the following doses of teduglutide: 0.01 (n = 6), 0.02 (n = 6), 0.1 (n = 5), or 0.2 mg · kg · day (n = 6), and compared with placebo (n = 9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (P < 0.05). There was a dose-dependent increase in weight per length of the remnant intestine (P < 0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (P < 0.001); however, functional and structural endpoints including activity of digestive enzymes, absorption of enteral nutrients, and immunohistochemistry (Ki67, villin, FABP2, ChgA, and GLP-2R) were not affected by the treatment. Teduglutide induces trophicity on the remnant intestine but has limited acute effects on functional endpoints. Significant effects of teduglutide on gut function may require a longer adaptation period and/or a more frequent administration of the peptide. In perspective, GLP-2 or its analogues may be relevant to improve intestinal adaptation in pediatric patients with short bowel syndrome.

Conditioned Canine Cadavers for Near-Natural Interprofessional Veterinary and Human Surgery Training.

Both medical and veterinary students find that the use of cadavers is critical to learning anatomical structures and surgical techniques. The use of human cadavers and the resulting user emotions are driven by serious ethical issues that are currently much less pronounced in veterinary education. Ethically sourced canine cadavers, thus, are more readily available. Aesthetics such as odor and visual appearance, though, influence both learner and educator motivation. We have investigated a way of delaying cadaver decomposition by post-mortem in situ, chemical-free, gastrointestinal lavage. We are convinced that canine cadavers, conditioned as described here, will improve the outcome of cadaver-based surgical skills training by facilitating preparation, reducing the number of required cadavers, postponing decomposition, improving the surgeon's haptic-tactile response to organ and tissue handling and suturing, and, possibly most importantly, increasing learners' and educators' focus due to the significantly improved aesthetics. We hypothesize that skill transfer for medical students and doctors, because of the similar abdominal anatomy, may be easier when training with conditioned canine cadavers as compared to artificial simulators or pigs in vivo.

Intratesticular and subcutaneous lidocaine alters the intraoperative haemodynamic responses and heart rate variability in male cats undergoing castration.

OBJECTIVE: To evaluate the usefulness of intratesticular and subcutaneous lidocaine in alleviating the intraoperative nociceptive response to castration, measured by pulse rate (PR) and mean arterial pressure (MAP), and to test the applicability of heart rate variability (HRV) analysis in assessing this response. STUDY DESIGN: Randomized, controlled, observer-blinded experimental trial. ANIMALS: Thirty-nine healthy male cats admitted for castration. METHODS: One group received general anaesthesia and served as control group (GA), while the treatment group (LA) additionally received local anaesthesia (lidocaine 2 mg kg(-1)) intratesticularly and subcutaneously. PR and MAP were recorded at anaesthesia baseline (T0), treatment (T1), incision left testicle (T2), traction on spermatic cord (T3), tightening of the autoligature and resection of the cord (T4), incision on the right side (T5), traction on spermatic cord (T6), and tightening of the autoligature and resection of cord (T7). HRV analysis was divided into three 5-minute intervals: baseline (H0), treatment (H1), and surgery (H2). RESULTS: There were significant increases in PR and MAP for both groups during surgery from T3 onwards; however, the increase in the treatment group (LA) was significantly lower than for the control group (GA). For HRV analysis, significant differences were found between groups in the following parameters during surgery: TP (total power), VLF (very low frequency), SDNN (standard deviation of NN intervals [= the interval between two consecutive R-waves in the ECG]), and TI (triangular index), which were lower in the LA group. Mean NN was significantly lower in the GA group, whereas LF (low frequency) and LFn (low frequency, normalized value) were lower in the LA group. HF (high frequency) and HFn (high frequency, normalized value) decreased significantly from H1 to H2 in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: The study showed that the nociceptive response to surgery was alleviated by the use of intratesticular and subcutaneous lidocaine and that HRV analysis is a promising research tool to estimate intraoperative nociception in cats during general anaesthesia.

Data-driven nonstationary signal decomposition approaches: a comparative analysis.

Signal decomposition (SD) approaches aim to decompose non-stationary signals into their constituent amplitude- and frequency-modulated components. This represents an important preprocessing step in many practical signal processing pipelines, providing useful knowledge and insight into the data and relevant underlying system(s) while also facilitating tasks such as noise or artefact removal and feature extraction. The popular SD methods are mostly data-driven, striving to obtain inherent well-behaved signal components without making many prior assumptions on input data. Among those methods include empirical mode decomposition and variants, variational mode decomposition and variants, synchrosqueezed transform and variants and sliding singular spectrum analysis. With the increasing popularity and utility of these methods in wide-ranging applications, it is imperative to gain a better understanding and insight into the operation of these algorithms, evaluate their accuracy with and without noise in input data and gauge their sensitivity against algorithmic parameter changes. In this work, we achieve those tasks through extensive experiments involving carefully designed synthetic and real-life signals. Based on our experimental observations, we comment on the pros and cons of the considered SD algorithms as well as highlighting the best practices, in terms of parameter selection, for the their successful operation. The SD algorithms for both single- and multi-channel (multivariate) data fall within the scope of our work. For multivariate signals, we evaluate the performance of the popular algorithms in terms of fulfilling the mode-alignment property, especially in the presence of noise.

Imaging of atherosclerosis with [64Cu]Cu-DOTA-TATE in a translational head-to-head comparison study with [18F]FDG, and Na[18F]F in rabbits.

Atherosclerosis is a chronic inflammatory disease of the larger arteries that may lead to cardiovascular events. Identification of patients at highest risk of cardiovascular events is challenging, but molecular imaging using positron emission tomography (PET) may prove useful. The aim of this study was to evaluate and compare head-to-head three different PET tracers. Furthermore, tracer uptake is compared to gene expression alterations of the arterial vessel wall. Male New Zealand White rabbits (control group; n = 10, atherosclerotic group; n = 11) were used for the study. Vessel wall uptake was assessed with the three different PET tracers: [18F]FDG (inflammation), Na[18F]F (microcalcification), and [64Cu]Cu-DOTA-TATE (macrophages), using PET/computed tomography (CT). Tracer uptake was measured as standardized uptake value (SUV), and arteries from both groups were analyzed ex vivo by autoradiography, qPCR, histology, and immunohistochemistry. In rabbits, the atherosclerotic group showed significantly higher uptake of all three tracers compared to the control group [18F]FDG: SUVmean 1.50 ± 0.11 versus 1.23 ± 0.09, p = 0.025; Na[18F]F: SUVmean 1.54 ± 0.06 versus 1.18 ± 0.10, p = 0.006; and [64Cu]Cu-DOTA-TATE: SUVmean 2.30 ± 0.27 versus 1.65 ± 0.16; p = 0.047. Of the 102 genes analyzed, 52 were differentially expressed in the atherosclerotic group compared to the control group and several genes correlated with tracer uptake. In conclusion, we demonstrated the diagnostic value of [64Cu]Cu-DOTA-TATE and Na[18F]F for identifying atherosclerosis in rabbits. The two PET tracers provided information distinct from that obtained with [18F]FDG. None of the three tracers correlated significantly to each other, but [64Cu]Cu-DOTA-TATE and Na[18F]F uptake both correlated with markers of inflammation. [64Cu]Cu-DOTA-TATE was higher in atherosclerotic rabbits compared to [18F]FDG and Na[18F]F.

Towards a model of biliary atresia - Pilot feasibility study in newborn piglets.

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA. Six piglets were subjected to abdominal surgery on day 4 after birth. The bile ducts were ligated, and the piglet were followed for up to 12 days. On day 12 the piglets were subjected to a hepatobiliary scintigraphy using the tracer radiolabeled Technetium(99m-tc)-mebrofenin, and blood samples were collected for biochemical profiling. Of the six piglets, hepatobiliary scintigraphy verified that two piglets (BDL) had no excretion of bile into the duodenum, i.e. full cholestasis with a hepatic extraction fraction of 84-87% and clearance time of 230-318 min. One piglet (SHAM) had bile excretion to the duodenum. In accordance with this, the BDL piglets had steatorrhea, and increased levels of bilirubin and gammaglutamyl transferase (GGT). The last three piglets were euthanized due to bile leakage or poor growth. Surgically induced cholestasis in young piglets, may offer an animal model that displays clinical characteristics of biliary atresia, including malabsorption, hyperbilirubinaemia, increased GGT and reduced hepatic excretory function. Following refinement, this animal model may be used to optimize feeding strategies to secure optimal nutrition and neurodevelopment for neonatal cholestasis/BA patients.

The quadriceps angle: reliability and accuracy in a fox (Vulpes vulpes) pelvic limb model.

OBJECTIVES: To evaluate the effect of measurement technique and limb positioning on quadriceps (Q) angle measurement, intra- and interobserver reliability, potential sources of error, and the effect of Q angle variation. STUDY DESIGN: Cadaveric radiographic study and computer modeling. ANIMALS: Pelvic limbs from red foxes (Vulpes vulpes). METHODS: Q angles were measured on hip dysplasia (HD) and whole limb (WL) view radiographs of each limb between the acetabular rim, mid-point (Q1: patellar center, Q2: femoral trochlea), and tibial tuberosity. Errors of 0.5-2.0 mm at measurement landmarks alone and in combination were modeled to identify the effect on Q angle. The effect of measured Q angles on the medial force exerted on the patella (F(MEDIAL)) was calculated. RESULTS: The HD position yielded significantly (P < .001) more medial Q angles than the WL position. No significant difference was observed between Q1 and Q2, but Bland-Altman plots indicated they were not equivalent. Intra- and interobserver agreement was substantial. Q2 errors were inherently greater than Q1: the mid-point and tibial tuberosity are the most important sources of Q angle variability. Increasing Q angles significantly increased the exerted F(MEDIAL) (P < .0001, gradient 1.7%). CONCLUSIONS: Measurements are reliable, but Q2 is more prone to error than Q1, and the 2 measurement techniques are not interchangeable. Positional errors must be kept below 1.3 mm (Q1) or 0.8 mm (Q2).

Pandemic precarity.

This editorial highlights how the Covid-19 pandemic has magnified precarity as a global life condition. At the same time, it has also emphasized inequality and exposed how some lives are more precarious than others. Those working in the so-called informal economy have been proportionally harder hit. In sub-Saharan Africa, where most of the economy is informal, many rely on improvisation tactics for everyday survival and well-being. Yet, in order to grasp these everyday tactics, the authors suggest that we move beyond two stereotypical ideas about Africa: the suffering and the resilient precariat. The discourse on precarity is often misleading and patronizing, pointing to the ways humans either suffer or transcend victimhood. In everyday lives, humans devise tactics - within larger structures and strategies beyond our control, such as the global pandemic - for making a living and creating lives worth living.

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.

Standing Still at Full Speed: Sports in an Overheated World.

In evolutionary biology, the "Red Queen Effect" refers to a form of inter- or intra-species competition where continuous improvement is necessary in order to survive and thrive, since the other species/individuals evolve. In sport, the same mechanism can be easily observed, and this article explores its implications. It discusses improved training regimes, scientific diets, innovative techniques enhancing performance, and technological improvements such as fibreglass skis. It argues that the upward spiral of improved achievement can be seen as an effect of the global market, or of the modern values of development and growth which are celebrated in modern sports. The world of competitive sports is not just an integral part of global capitalism, but it also mirrors and mimes its internal logic. The kinship between sport and war is obvious, and many sports grew out of military training. But since much of the world has been spared the horrors of war for generations, in the very same period that capitalism has become ever more hegemonic and globalised, sports in the 21st century have come to resemble market competition more than bloody events on the battlefield. Not least for this reason, the treadmill paradox, or Red Queen effect, easily discernable in market economies as a driver for change, whether progressive or destructive or both, can fruitfully be applied as an analytical lens through which to view sport. The question nevertheless remains to be answered as to whether the improved achievements of athletes lead to an improved spectator experience or the opposite. In this question lies an inherent paradox of contemporary world civilisation, with a literal as well as a metaphorical bearing on the critique of the unsustainable growth economy.

Multimodal soft tissue markers for bridging high-resolution diagnostic imaging with therapeutic intervention.

Diagnostic imaging often outperforms the surgeon's ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.

Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model.

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.

The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets.

BACKGROUND: Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol-remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia. Sixteen healthy female piglets (25-34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol-remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation). RESULTS: During propofol-remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0.02). In contrast, cerebral oxygen saturation (NIRS) fell significantly in NBP following phenylephrine (P = 0.003), and following both norepinephrine (P = 0.02) and phenylephrine (P = 0.002) in LBP. Blood pressure increase by both norepinephrine and phenylephrine during propofol-remifentanil-dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group. CONCLUSIONS: Cerebral partial pressure of oxygen measured by Licox increased significantly in concert with the vasopressor induced increases in blood pressure in healthy piglets with both normal and low blood pressure. Cerebral oxygenation assessed by intracerebral Licox and transcranial NIRS showed opposing results to vasopressor infusions.

Advanced Electrocardiogram Analysis in the Amitriptyline-poisoned Pig Treated with Activated Charcoal Haemoperfusion.

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.

Minimal Enteral Nutrition to Improve Adaptation After Intestinal Resection in Piglets and Infants.

BACKGROUND: Minimal enteral nutrition (MEN) may induce a diet-dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated in patients with short bowel syndrome. METHODS: In experiment 1, 3-day-old piglets with 50% distal small intestinal resection were fed parenteral nutrition (PN, n = 10) or PN plus MEN given as either colostrum (PN-COL, n = 5) or formula (PN-FORM, n = 9) for 7 days. Intestinal nutrient absorption and histomorphometry were performed. In experiment 2, tolerance and feasibility of colostrum supplementation were tested in a pilot study on 5 infants who had undergone intestinal resection, and they were compared with 5 resected infants who served as controls. RESULTS: In experiment 1, relative wet-weight absorption and intestinal villus height were higher in PN-COL vs PN (53% vs 23% and 362 ± 13 vs 329 ± 7 µm, P < .05). Crypt depth and tissue protein synthesis were higher in PN-COL (233 ± 7 µm, 22%/d) and PN-FORM (262 ± 13 µm, 22%/d) vs PN (190 ± 4 µm, 9%/d, both P < .05). In experiment 2, enteral colostrum supplementation was well tolerated, and no infants developed clinical signs of cow's milk allergy. CONCLUSION: Minimal enteral nutrition feeding with bovine colostrum and formula induced similar intestinal adaptation after resection in piglets. Colostrum was well tolerated by newly resected infants, but the clinical indication for colostrum supplementation to infants subjected to intestinal resection remains to be determined.

The effect of dexmedetomidine on cerebral perfusion and oxygenation in healthy piglets with normal and lowered blood pressure anaesthetized with propofol-remifentanil total intravenous anaesthesia.

BACKGROUND: During anaesthesia and surgery, in particular neurosurgery, preservation of cerebral perfusion and oxygenation (CPO) is essential for normal postoperative brain function. The isolated effects on CPO of either individual anaesthetic drugs or entire anaesthetic protocols are of importance in both clinical and research settings. Total intravenous anaesthesia (TIVA) with propofol and remifentanil is widely used in human neuroanaesthesia. In addition, dexmedetomidine is receiving increasing attention as an anaesthetic adjuvant in neurosurgical, intensive care, and paediatric patients. Despite the extensive use of pigs as animal models in neuroscience and the increasing use of both propofol-remifentanil and dexmedetomidine, very little is known about their combined effect on CPO in pigs with uninjured brains. This study investigates the effect of dexmedetomidine on CPO in piglets with normal and lowered blood pressure during background anaesthesia with propofol-remifentanil TIVA. Sixteen healthy female Danish pigs (crossbreeds of Danish Landrace, Yorkshire and Duroc, 25-34 kg) were used. Three animals were subsequently excluded. The animals were randomly allocated into one of two groups with either normal blood pressure (NBP, n = 6) or with induced low blood pressure (LBP, n = 7). Both groups were subjected to the same experimental protocol. Intravenous propofol induction was performed without premedication. Anaesthesia was maintained with propofol-remifentanil TIVA, and later supplemented with continuous infusion of dexmedetomidine. Assessments of cerebral perfusion obtained by laser speckle contrast imaging (LSCI) were related to cerebral oxygenation measures (PbrO2) obtained by an intracerebral Clark-type Licox probe. RESULTS: Addition of dexmedetomidine resulted in a 32% reduction in median PbrO2 values for the LBP group (P = 0.03), but no significant changes in PbrO2 were observed for the NBP group. No significant changes in LSCI readings were observed in either group between any time points, despite a 28% decrease in the LBP group following dexmedetomidine administration. Caval block resulted in a significant (P = 0.02) reduction in median MAP from 68 mmHg (range 63-85) at PCB to 58 mmHg (range 53-63) in the LBP group, but no significant differences in either PbrO2 or LSCI were observed due to this intervention (P = 0.6 and P = 0.3 respectively). CONCLUSIONS: Addition of dexmedetomidine to propofol-remifentanil TIVA resulted in a significant decrease in cerebral oxygenation (PbrO2) measurements in piglets with lowered blood pressure. Cerebral perfusion (LSCI) did not decrease significantly in this group. In piglets with normal blood pressure, no significant changes in cerebral perfusion or oxygenation were seen in response to addition of dexmedetomidine to the background anaesthesia.