Recommendations for safe anaesthesia are common in medical practice, have been formulated for traditional laboratory species, i.e. rodents, but do not exist for laboratory pigs, sheep, goats and cattle. The guidelines presented here were commissioned by the Federation of European Laboratory Animal Science Associations (FELASA) and serve to underscore EU Directive 2010/63/EU (Article 14) which require that, 'procedures are carried out with general or local anaesthesia and analgesia or another appropriate method to ensure pain, suffering and distress are kept to a minimum'. The guidelines are based on a review of: (i) medical and veterinary medical guidelines promoting safe anaesthetic practice; (ii) scientific literature pertaining to anaesthesia and analgesia in pigs, sheep, goats and cattle; and (iii) a consideration of the ethical, legal and scientific requirements when anaesthetizing laboratory animals. The guidelines aim to make recommendations for the provision of safe, practical and effective anaesthesia and analgesia to laboratory pigs and ruminants. Recommended standards for sedation and restraint (I), general principles of anaesthesia (II), monitoring anaesthesia (III) and pain assessment (IV) in the same species have been described by this working group (WG) and are set out in four parts in this document.

Farmed animals have been used in anatomical and physiological studies since classical times, presumably for reasons of widespread availability, the benefits of comparative studies and size-relevance. Some forms, e.g. fish and cephalopoda, were probably used for their curiosity value alone. From earliest times, observers have complained that the pain and suffering experienced by animals involved in noxious studies were immorally cruel and undermined the value of scientific observations, although these were not sufficient reasons to stop the practice. That farmed animals were reared primarily for consumption and so were destined to experience profound unpleasantness during the slaughter and butchery process probably assuaged the concerns of those conducting farmed animal vivisection but not the pain nor suffering endured by the animals involved. The introduction of anaesthetics in the mid-nineteenth century went some way to improve matters, although an increased awareness of sentience as a characteristic of an ever-increasing range of non-human animals-farmed or otherwise-and their inclusion into a moral community was probably more influential. The animal rights movement of the late twentieth century focused societal interest into the fate of all animals involved in biomedical research and through numerous strategies prompted the creation of legislation protecting laboratory animals. This chapter encourages the reader to imagine the experiences of farmed animals undergoing biomedical research throughout history while identifying the major developments that have arisen to minimize their pain and suffering.

Magnesium regulates myocardial depolarisation, vascular tone, neuromuscular function and provides analgesia. This study examined its analgesic and haemodynamic effects, comparing the effects of intravenous saline 0.9% (NaCl; control n = 8) and magnesium (n = 7) infusions in minipigs undergoing thoracotomy. Preoperative single-housed activity was recorded for 1 h. Intraoperatively, arterial blood pressure (BP) and heart rate (HR) were recorded once telemetry was established; data from the final 60 min of anaesthesia were compared between groups. Postoperative activity, HR and BP were recorded continuously using in-pen CCTV and telemetry, respectively. Indicators of pain, including HR and BP were sampled after tracheal extubation (TTE) at +0.5, +2.5, +4.5, +6, +8.5, +15.5, +17.5, +19.5, +20, +23, +25.5, +26 and +29 h. Changes in HR and BP before and after analgesia at TTE +6, +17.5, +23 and +29 h, and pre- and post-pain assessments at TTE +2.5, +6, +17.5, +20, +23, +26 and +29 h were compared using a paired t-test. During anaesthesia, no electrocardiography derangements were noted. There was no difference between groups in the area under the curve for any cardiovascular variable. Magnesium-treated animals had an increased incidence of hypotension during anaesthesia. Postoperatively, activity decreased significantly for both groups for duration (all time points) and frequency (TTE +0.5, +4.5, +8.5, +15.5 h), but no treatment effect was observed. Pain scores were comparable between groups. Following pain assessment and analgesia administration at TTE +17.5, Group NaCl had significant increases in HR and mean arterial pressure The magnesium dose evaluated produced no harm nor obvious benefit.

Cardiovascular disease causes vascular dementia and contributes to most clinical dementia. This is embodied in the concept of vascular contributions to cognitive impairment and dementia (VCID). The potent endogenous peptide endothelin-1 (ET1) causes small artery vasoconstriction and fibrosis. ET1 is implicated in microvascular disease and in VCID. There are few experimental animal models relevant to VCID [Hainsworth et al. 2017]. Pigs are higher mammals with a gyrencephalic brain and extensive subcortical white matter. We engineered domestic pigs carrying additional copies of the ET1-encoding gene EDN1 under a Tet-ON promotor, by lentiviral injection into blastocysts. We induced transgene expression for up to 8 days using oral doxycycline in young adults. We studied ET1-overexpressing (n = 6, 3F/3M, mean±SD age 184±61 days) and control animals (n = 5, 3F/2M, 149±41 days). Following doxycycline treatment we observed a wide range of transgene expression at mRNA level. Antibody labelling indicated a spectrum of ET1 abundance in brain and heart tissue. Heart weight was 460±106 g in ET1-overexpressing pigs and 394±25 g in controls. Brain weight: 104±14.4 g in ET1-overexpressing, 101±9.0 in controls. We will report phenotypes relevant to inflammation and blood vessel fibrosis. Adult-onset EDN1 induction in domestic pigs produces ET1 overexpression that is well-tolerated to 8 days. Reference : Hainsworth AH, et al. (2017) BMC Med . 15 (1):16. Translational models for vascular cognitive impairment: a review including larger species.

Acute compartment syndrome (ACS) is an orthopaedic emergency that occurs after limb trauma, where increased pressure in muscle compartments disrupts blood flow, risking nerve and muscle damage. Timely diagnosis is essential to avoid permanent harm, but current methods are either invasive, expensive, or subjective. The gold standard remains invasive intracompartmental pressure (IComP) measurement, with other approaches lacking enough evidence to replace it. This study proposes two mechanical tools - mechanical indentation and image-based strain mapping - as simplified methods for ACS assessment. Our work started by establishing a porcine model of ACS, involving intracompartmental gelofusine infusion and pressure measurement in selected muscles of the appendicular skeleton. The IComP could then be adjucted as required from 0 - 40 mmHg (which exceeds the diagnostic threshold of 30 mmHg). With a consistent animal model of ACS, we sought to identify if mechanical methods could measure the internal muscle pressure changes from the surface of the skin. Using a custom-made handheld indenter, we examined the skin overlying muscles during IComP manipulations. Whilst we observed some changes in the mechanical moduli extracted from the indentation force-displacement curves, there was no statistical difference in this method changing pressure. We then used a single-camera digital image correlation (DIC), which showed that as internal pressure increased, corresponding surface skin strains increased. At 30 mmHg the skin reached an average strain of approximately 1.5% although local strains were higher due to an uneven distribution of pressure in the muscle (one reason for the indenter results being so variable). This approach therefore provides a non-invasive diagnostic threshold for ACS in our model and has the potential for clinical use in human patients. STATEMENT OF SIGNIFICANCE: In this study, we established a porcine model of acute compartment syndrome (ACS) to evaluate the mechanical response of skin and muscle under increased intracompartmental pressure (IComP). We developed and tested two non-invasive diagnostic approaches-mechanical indentation and single-camera digital image correlation (DIC)-to assess internal pressure changes from the skin surface. While the indentation method exhibited variability due to uneven pressure distribution, the DIC approach demonstrated a clear relationship between increased IComP and surface strain, identifying a diagnostic threshold of approximately 1.5% strain at 30 mmHg. These findings provide a foundation for the development of non-invasive ACS diagnostic tools that use the mechanical properties of the tissue as a health biomarker (e.g., wearable sensors), offering potential for simplified and cost-effective clinical application.

Apart from his major contribution to teaching and clinical service at the Dick Vet's Hospital for Small Animals, he was generous in his support of students, charitable activities and community projects.

Functional gastrointestinal (GI) disease associated with abnormal GI motility has an adverse impact on the quality of life of those affected. High-resolution manometry has improved the diagnosis of these conditions, enabling motility measurement, but these tools are limited in that they cannot access the entire length of the GI tract. Other solutions, such as the SmartPill ingestible motility capsule, only measure the transit times between the regions of the GI tract and provide information on the luminal component of GI pressure. Measuring both luminal and contractile pressure caused by peristalsis would improve the diagnosis of abnormal motility. Here, we report an ingestible capsule encapsulated with a flexible pressure sensor array. The capsule can detect changes in both contractile and luminal GI pressure in an in vitro peristaltic tissue phantom and in porcine animal models. These findings promise high-resolution, sensitive, multisite pressure measurements currently not possible with other ingestible motility capsules.

Ovine pulmonary adenocarcinoma (OPA) is an infectious, neoplastic lung disease of sheep that causes significant animal welfare and economic issues throughout the world. Understanding OPA pathogenesis is key to developing tools to control its impact. Central to this need is the availability of model systems that can monitor and track events after Jaagsiekte sheep retrovirus (JSRV) infection. Here, we report the development of an experimentally induced OPA model intended for this purpose. Using three different viral dose groups (low, intermediate and high), localised OPA tumour development was induced by bronchoscopic JSRV instillation into the segmental bronchus of the right cardiac lung lobe. Pre-clinical OPA diagnosis and tumour progression were monitored by monthly computed tomography (CT) imaging and trans-thoracic ultrasound scanning. Post mortem examination and immunohistochemistry confirmed OPA development in 89% of the JSRV-instilled animals. All three viral doses produced a range of OPA lesion types, including microscopic disease and gross tumours; however, larger lesions were more frequently identified in the low and intermediate viral groups. Overall, 31% of JSRV-infected sheep developed localised advanced lesions. Of the sheep that developed localised advanced lesions, tumour volume doubling times (calculated using thoracic CT 3D reconstructions) were 14.8 ± 2.1 days. The ability of ultrasound to track tumour development was compared against CT; the results indicated a strong significant association between paired CT and ultrasound measurements at each time point (R2 = 0.799, p < 0.0001). We believe that the range of OPA lesion types induced by this model replicates aspects of naturally occurring disease and will improve OPA research by providing novel insights into JSRV infectivity and OPA disease progression.

Veterinary RecordVolume 192, Issue 4 p. 174-175 Veterinary Ethics Promoting good ethical practice David Morton, Corresponding Author David Morton group chair [email protected] Search for more papers by this authorKate Allen, Kate Allen group secretary [email protected] Search for more papers by this authorBeth Jinks, Beth Jinks RCVS representativesSearch for more papers by this authorMike Herrtage, Mike Herrtage RCVS representativesSearch for more papers by this authorMichael Clark, Michael Clark University of Nottingham representativesSearch for more papers by this authorRichard Lea, Richard Lea University of Nottingham representativesSearch for more papers by this authorEddie Clutton, Eddie Clutton University of Edinburgh representativesSearch for more papers by this authorKiterie Faller, Kiterie Faller University of Edinburgh representativesSearch for more papers by this authorStephen Greenhalgh, Stephen Greenhalgh University of Edinburgh representativesSearch for more papers by this authorPeter Fordyce, Peter Fordyce University of Cambridge representativeSearch for more papers by this authorSarah Wolfensohn, Sarah Wolfensohn University of Surrey representativesSearch for more papers by this authorChris Stevens, Chris Stevens University of Surrey representativesSearch for more papers by this authorPamela Gillick, Pamela Gillick University College Dublin representativeSearch for more papers by this authorNicola Menzies-Gow, Nicola Menzies-Gow Royal Veterinary College representativeSearch for more papers by this authorDavid Killick, David Killick University of Liverpool representativeSearch for more papers by this authorJoanna Morris, Joanna Morris University of Glasgow representativeSearch for more papers by this authorDavid Martin, David Martin IVC Evidensia representativeSearch for more papers by this authorLuisa De Risio, Luisa De Risio Linnaeus representativeSearch for more papers by this authorJo Murrell, Jo Murrell CVS Group representativeSearch for more papers by this author David Morton, Corresponding Author David Morton group chair [email protected] Search for more papers by this authorKate Allen, Kate Allen group secretary [email protected] Search for more papers by this authorBeth Jinks, Beth Jinks RCVS representativesSearch for more papers by this authorMike Herrtage, Mike Herrtage RCVS representativesSearch for more papers by this authorMichael Clark, Michael Clark University of Nottingham representativesSearch for more papers by this authorRichard Lea, Richard Lea University of Nottingham representativesSearch for more papers by this authorEddie Clutton, Eddie Clutton University of Edinburgh representativesSearch for more papers by this authorKiterie Faller, Kiterie Faller University of Edinburgh representativesSearch for more papers by this authorStephen Greenhalgh, Stephen Greenhalgh University of Edinburgh representativesSearch for more papers by this authorPeter Fordyce, Peter Fordyce University of Cambridge representativeSearch for more papers by this authorSarah Wolfensohn, Sarah Wolfensohn University of Surrey representativesSearch for more papers by this authorChris Stevens, Chris Stevens University of Surrey representativesSearch for more papers by this authorPamela Gillick, Pamela Gillick University College Dublin representativeSearch for more papers by this authorNicola Menzies-Gow, Nicola Menzies-Gow Royal Veterinary College representativeSearch for more papers by this authorDavid Killick, David Killick University of Liverpool representativeSearch for more papers by this authorJoanna Morris, Joanna Morris University of Glasgow representativeSearch for more papers by this authorDavid Martin, David Martin IVC Evidensia representativeSearch for more papers by this authorLuisa De Risio, Luisa De Risio Linnaeus representativeSearch for more papers by this authorJo Murrell, Jo Murrell CVS Group representativeSearch for more papers by this author First published: 17 February 2023 https://doi.org/10.1002/vetr.2761Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume192, Issue418/25 February 2023Pages 174-175 RelatedInformation

Pigs are extensively used in biomedical research and frequently undergo procedures requiring general anaesthesia and analgesia. For species-related and technical reasons, this can often be challenging and requires both knowledge of and expertise in applied behavior and animal welfare science, as well as anesthesia and analgesia. An understanding of basic physiology, pharmacology and the relevant regulatory limitations are further prerequisites to ensuring animal welfare requirements while achieving scientific objectives. This chapter aims to provide a comprehensive overview of approaches, techniques, training and protocols to assist research groups in achieving better anesthetic and analgesic care for their laboratory pigs; and thereby produce higher quality data in more reproducible studies, primarily through promoting experimental refinement.

This article examines the ethical principles underlying the Declaration of Helsinki as an internationally agreed justificatory framework for human medical research.The aim of the analysis is to consider the potential usefulness of these principles for defining an internationally agreed ethical 'best practice' in clinical veterinary research (CVR).It is suggested that the specific ethical responsibilities of the clinician to protect the interests of their patient when conducting medical research may be translated into the veterinary setting.Through exploring risk and harm, unproven interventions, vulnerability and informed consent, the article identifies the ethical risks of CVR.It is shown that veterinary regulators in the UK and the European Union have addressed these concerns to varying degrees; however, disagreements over the appropriateness of specific CVR practices are identified.A commitment to collaborative exploration of the benefits and challenges of implementing a Declaration of Helsinki for Animals is proposed.

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1–/–) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1–/– mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.

Descriptions of measures taken to optimize animal welfare are often absent from scientific reports of animal experiments. One reason may be that journal guidelines inadequately compel authors to provide such information. In this study, online English language versions of the 'Guidelines to authors' (GTAs) from 54 national biomedical journals were examined for neutral (unrelated to welfare) and non-neutral keywords referring to: animal welfare; the '3Rs'; the ARRIVE (2010) guidelines, and regulations pertaining to animal experimentation. Journals were selected from nine countries (UK, US, China, Canada, India, Brazil, Germany, Japan and Australia) and seven biomedical specialties (oncology, rheumatology, surgery, pharmacology, medicine, anaesthesia and veterinary medicine). Total GTA word counts varied from 1137 to 31,609. The keyword count identified per category were expressed per myriad (10,000) of total word count. One-way analyses of variance followed by post hoc Tukey pairwise comparisons revealed greater non-neutral per myriad word counts for (a) veterinary GTAs compared with medicine, oncology, rheumatology or surgery; (b) British, compared with Australian, Canadian, German and Japanese GTAs; and (c) no differences between non-neutral categories. The English language versions of GTAs of British and veterinary medical journals contain more words associated with animal welfare, the 3Rs and the ARRIVE guidelines than those from eight other countries and six other medical specialities. The exclusion of 'national' language versions from analysis precludes attempts to identify national differences in attitudes to laboratory animal welfare.

Pigs are used to model humans in gastrointestinal (GI) studies because of their comparable size, physiology and behaviour: both are monogastric omnivores. A porcine surgical model for testing novel, tethered ultrasound capsule endoscopes (USCE) requires a clean, motile small intestine. Recommendations for human GI tract preparation before the mechanically similar process of video capsule endoscopy describe using oral purgatives, while high-carbohydrate drinks are recommended before colorectal surgery. Reports of the GI preparation of pigs exist but lack technical details, that is, administration, efficacy and side effects. This report details feeding a high-energy liquid diet to 11 female pigs undergoing surgery and USCE which was readily accepted and easily administered, and which produced a clean, motile small intestine and caused no detectable physiological/behavioural abnormalities.