Animal welfare requirements in publishing guidelines.

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.

Noninvasive Detection of Ischemic Vascular Damage in a Pig Model of Liver Donation After Circulatory Death.

BACKGROUND AND AIMS: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. APPROACH AND RESULTS: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. CONCLUSIONS: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

Feeding management before gastrointestinal studies in pigs.

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.

An Anglocentric History of Anaesthetics and Analgesics in the Refinement of Animal Experiments.

Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK) Parliamentary debates on vivisection in the mid-19th century and viewed as "indisputable refinements in animal experimentation" (Russell and Burch 1959), it seemed that an analysis of their role was overdue. This commentary has, in interweaving the history of animal experimentation in the UK with the evolution of anaesthesia, attempted to: (1) clarify the evidence for Russell and Burch's view; and (2) evaluate anaesthesia's ongoing contribution to experimental refinement. The history that emerges reveals that the withholding or misuse of anaesthetics and, or analgesics from laboratory animals in the UK has had a profound effect on scientists and indirectly on the attitudes of the British public in general, becoming a major driver for the establishment of the anti-vivisection movement and subsequently, the Cruelty to Animals Act (1876)-the world's first legislation for the regulation of animal experimentation. In 1902, the mismanaged anaesthetic of a dog in the Department of Physiology, University College London resulted in numerous events of public disorder initiated by medical students against the police and a political coalition of anti-vivisectionists, trade unionists, socialists, Marxists, liberals and suffragettes. The importance of anaesthesia in animal experiments was sustained over the following 150 years as small mammalian species gradually replaced dogs and cats as the principle subjects for vivisection. In discussing experimental refinement in their 1959 report, "The Principles of Humane Experimental Technique" Russell and Burch described anaesthetics as "… the greatest single advance in humane technique, (which) has at the same time been virtually indispensable for the advance of experimental biology". Since then, the role of anaesthetics and in particular analgesics has become an unavoidable consideration whenever animal experiments are planned and conducted. This has been accompanied by a proliferation of training and educational programmes in laboratory animal anaesthesia.

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning.

Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

Efficacy of an organophosphorus hydrolase enzyme (OpdA) in human serum and minipig models of organophosphorus insecticide poisoning.

Objectives: Current therapeutic options for organophosphorus (OP) insecticide self-poisoning including atropine and oximes are inadequate and case fatality may exceed 20%. An OP hydrolase enzyme, OpdA, has been used for environmental cleansing of OP insecticides and prevented death in rat and non-human primate models of OP insecticide poisoning if given very quickly after exposure. We here tested OpdA's ability to break down OP insecticides in human serum and in clinically relevant minipig models of OP insecticide poisoning.Methods: Human serum was spiked with seven diverse WHO Class II OP insecticides (chlorpyrifos, quinalphos, diazinon, dimethoate, fenthion, phenthoate, and profenofos) and the effect of OpdA on degradation measured. The pharmacodynamic and clinical effects of OpdA treatment were studied in Gottingen minipigs orally poisoned with agricultural formulations of dimethoate EC40 or methyl parathion EC60; pharmacodynamic effects were also assessed in profenofos EC50-poisoned pigs.Results: OpdA effectively hydrolysed OP insecticides in human serum, with rates varying from 856 (SD 44) down to 0.107 (SD 0.01) moles of substrate hydrolysed/mole of enzyme/sec (kcat) for quinalphos and phenthoate, respectively, although at rates 2-3 log orders less than found in vitro in buffered solution. It showed clinical benefit in minipig models, reducing the dose of noradrenaline required to sustain an adequate mean arterial pressure after dimethoate (mean 0.149 [SD 0.10] µg/kg/h vs. 1.07 [SD 0.77] µg/kg/h, p < .0001) and methyl parathion (mean 0.077 [SD 0.08] µg/kg/h vs. 0.707 [SD 0.49] µg/kg/h, p < .0001) poisoning. OpdA reduced blood OP insecticide concentration and acetylcholinesterase inhibition after poisoning by dimethoate, methyl parathion, and profenofos insecticides.Conclusions:In vitro incubation of OpdA in human serum showed hydrolysis of diverse OP insecticides, although at lower rates than found in buffer solutions. This activity results in clinical and pharmacodynamic efficacy in vivo against several OP insecticides. These results support the testing of OpdA in further animal models before considering human trials to determine whether it may become an urgently required novel therapeutic agent for OP insecticide self-poisoning.

A Novel Translational Ovine Pulmonary Adenocarcinoma Model for Human Lung Cancer.

In vitro cell line and in vivo murine models have historically dominated pre-clinical cancer research. These models can be expensive and time consuming and lead to only a small percentage of anti-cancer drugs gaining a license for human use. Large animal models that reflect human disease have high translational value; these can be used to overcome current pre-clinical research limitations through the integration of drug development techniques with surgical procedures and anesthetic protocols, along with emerging fields such as implantable medical devices. Ovine pulmonary adenocarcinoma (OPA) is a naturally-occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease has similar histological classification and oncogenic pathway activation to that of human lung adenocarcinomas making it a valuable model for studying human lung cancer. Developing OPA models to include techniques used in the treatment of human lung cancer would enhance its translational potential, making it an excellent research tool in assessing cancer therapeutics. In this study we developed a novel OPA model to validate the ability of miniaturized implantable O2 and pH sensors to monitor the tumor microenvironment. Naturally-occurring pre-clinical OPA cases were obtained through an on-farm ultrasound screening programme. Sensors were implanted into OPA tumors of anesthetized sheep using a CT-guided trans-thoracic percutaneous implantation procedure. This study reports the findings from 9 sheep that received sensor implantations. Time taken from initial CT scans to the placement of a single sensor into an OPA tumor was 45 ± 5 min, with all implantations resulting in the successful delivery of sensors into tumors. Immediate post-implantation mild pneumothoraces occurred in 4 sheep, which was successfully managed in all cases. This is, to the best of our knowledge, the first description of the use of naturally-occurring OPA cases as a pre-clinical surgical model. Through the integration of techniques used in the treatment of human lung cancer patients, including ultrasound, general anesthesia, CT and surgery into the OPA model, we have demonstrated its translational potential. Although our research was tailored specifically for the implantation of sensors into lung tumors, we believe the model could also be developed for other pre-clinical applications.

Transcranial bioimpedance measurement in horses: a pilot study.

OBJECTIVE: This pilot study aimed to evaluate the feasibility of transcranial bioimpedance (TCBI) measurement and variability of TCBI values in healthy conscious horses and to study effects of body position and time on TCBI in anaesthetized horses. STUDY DESIGN: Prospective, observational study. ANIMALS: A total of four research horses and 16 client-owned horses presented for surgery. METHODS: After establishing optimal electrode position using computed tomography scans of cadaver heads, TCBI [described using impedance at zero frequency, R0, (Ω)] was measured in four conscious, resting horses to investigate the feasibility and changes in TCBI over time (80 minutes). Data were compared using a paired t test. TCBI was then measured throughout anaesthesia (duration 92 ± 28 minutes) in 16 horses in dorsal and lateral recumbency. Data were analysed using a general linear model; gamma regression was chosen as a model of characteristic impedance [Zc; (Ω)] against time. Data are presented as mean ± standard deviation. RESULTS: No change in R0 was seen in conscious horses (age = 15.3 ± 7.3 years, body mass = 512 ± 38 kg) over 80 minutes. The technique was well tolerated and caused no apparent adverse effects. In 16 horses (age = 7.4 ± 4.7 years; body mass = 479 ± 134 kg) anaesthetized for 92 ± 28 minutes, Zc fell during anaesthesia, decreasing more in horses in lateral recumbency than in horses in dorsal recumbency (p = 0.008). There was no relationship between Zc and body mass or age. CONCLUSIONS AND CLINICAL RELEVANCE: TCBI is readily measured in horses. TCBI did not change with time in conscious horses, but decreased with time in anaesthetized horses; this change was greater in horses in lateral recumbency, indicating that TCBI changes in anaesthetized horses may be related to the effects of recumbency, general anaesthesia, surgery or a combination of these factors.

Comparison of Brody's formula with respiratory gas analysis for estimating oxygen consumption in anaesthetized dogs.

OBJECTIVE: To determine agreement in oxygen consumption (V˙O2) values calculated using Sykes' formula V˙O2 = (FiO2 - Fe'O2) * V˙E (where Fi and Fe are the inspired and end-tidal fractional concentrations of O2, respectively, and V˙E is minute volume) with values derived using Brody's formula (V˙O2 = 10 kg3/4). It was hypothesized that the two methods would not yield statistically significant differences in calculated values. STUDY DESIGN: Prospective, clinical, pilot study. ANIMALS: A total of 22 client-owned dogs. METHODS: Dogs undergoing surgery were anaesthetized with either isoflurane or sevoflurane. The V˙E, FiO2 and Fe'O2 were measured during mechanical ventilation of the lungs (tidal volume 10 mL kg-1; respiratory rate: 8-12 breaths minute-1). Oesophageal temperature was maintained between 37.0 °C and 38.5 °C. Values for V˙O2 derived by Sykes' and Brody's methods were compared and agreement was determined using Bland-Altman analysis. RESULTS: Mean V˙O2 values were 4.67 ± 0.51 mL kg-1 minute-1 and 5.32 ± 1.69 mL kg-1 minute-1 calculated using Brody's formula and Sykes' equation, respectively. There was greater variability in the values obtained from Sykes' equation. The Bland-Altman plot revealed a proportional error with correlation but poor agreement between values. CONCLUSIONS AND CLINICAL RELEVANCE: Both methods yielded V˙O2 values of approximately 5 mL kg-1minute-1 with no statistically significant differences between the two methods.

Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine model: a pharmacokinetic and clinical study.

BACKGROUND: Colchicine poisoning is commonly lethal. Colchicine-specific Fab fragments increase rat urinary colchicine clearance and have been associated with a good outcome in one patient. We aimed to develop a porcine model of colchicine toxicity to study the pharmacokinetics and efficacy of ovine Fab. METHODS: A Göttingen minipig critical care model was established and serial blood samples taken for colchicine and Fab pharmacokinetics, clinical chemistry, and haematology. Animals were euthanised when the mean arterial pressure fell below 45 mmHg without response to vasopressor, or at study completion. RESULTS: Initial studies indicated that oral dosing produced variable pharmacokinetics and time-to-euthanasia. By contrast, intravenous infusion of 0.25 mg/kg colchicine over 1 h produced reproducible pharmacokinetics (AUC0-20 343 [SD = 21] µg/L/h), acute multi-organ injury, and cardiotoxicity requiring euthanasia a mean of 22.5 (SD = 3.2) h after dosing. A full-neutralising equimolar Fab dose given 6 h after the infusion (50% first hour, 50% next 6 h [to reduce renal-loss of unbound Fab]) produced a 7.35-fold increase in plasma colchicine (AUC0-20 2,522 [SD = 14] µg/L/h), and removed all free plasma colchicine, but did not prevent toxicity (euthanasia at 29.1 [SD = 3.4] h). Earlier administration over 1 h of the full-neutralising dose, 1 or 3 h after the colchicine, produced a 12.9-fold (AUC0-20 4,433 [SD = 607] µg/L/h) and 6.0-fold (AUC0-20 2,047 [SD = 51] µg/L/h) increase in plasma colchicine, respectively, absence of free plasma colchicine until 20 h, and survival to study end without marked cardiotoxicity. CONCLUSIONS: Colchicine-specific Fab given early, in equimolar dose, bound colchicine, eliciting its movement into the blood, and preventing severe toxicity. Clinical studies are now needed to determine how soon this antidote must be given to work in human poisoning.

PREPARE: guidelines for planning animal research and testing.

There is widespread concern about the quality, reproducibility and translatability of studies involving research animals. Although there are a number of reporting guidelines available, there is very little overarching guidance on how to plan animal experiments, despite the fact that this is the logical place to start ensuring quality. In this paper we present the PREPARE guidelines: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: formulation, dialogue between scientists and the animal facility, and quality control of the various components in the study. Some topics overlap and the PREPARE checklist should be adapted to suit specific needs, for example in field research. Advice on use of the checklist is available on the Norecopa website, with links to guidelines for animal research and testing, at https://norecopa.no/PREPARE .

LC-MS/MS quantification of free and Fab-bound colchicine in plasma, urine and organs following colchicine administration and colchicine-specific Fab fragments treatment in Göttingen minipigs.

Clinical evaluation of a colchicine specific antigen-binding fragment (Fab) in order to treat colchicine poisoning required the development of an accurate method allowing quantification of free and Fab-bound colchicine in plasma and urine, and free colchicine in tissues, to measure colchicine redistribution after Fab administration. Three methods have been developed for this purpose, and validated in plasma, urine and liver: total colchicine was determined after denaturation of Fab by dilution in water and heating; free colchicine was separated from Fab-bound colchicine by filtration with 30KDa micro-filters; tissues were homogenized in a tissue mixer. Deuterated colchicine was used as internal standard. Samples were extracted by liquid-liquid extraction and analyzed with a LC-MS/MS. LOQ were 0.5ng/mL in plasma and urine for free and total colchicine and 5pg/mg in tissues. The methods were linear in the 0.5-100ng/mL range in plasma and urine, and 5-300pg/mg in tissues with determination coefficients>0.99. Precision and accuracy of QC samples presented a CV<9.4%. The methods require only 200µL of sample and allow a high throughput due to short analytical run (2min). These methods were successfully applied to a pig intoxicated with colchicine and treated with colchicine specific Fab fragments.

A Review of Pain Assessment in Pigs.

There is a moral obligation to minimize pain in pigs used for human benefit. In livestock production, pigs experience pain caused by management procedures, e.g., castration and tail docking, injuries from fighting or poor housing conditions, "management diseases" like mastitis or streptococcal meningitis, and at parturition. Pigs used in biomedical research undergo procedures that are regarded as painful in humans, but do not receive similar levels of analgesia, and pet pigs also experience potentially painful conditions. In all contexts, accurate pain assessment is a prerequisite in (a) the estimation of the welfare consequences of noxious interventions and (b) the development of more effective pain mitigation strategies. This narrative review identifies the sources of pain in pigs, discusses the various assessment measures currently available, and proposes directions for future investigation.

Review of Practices Reported for Preoperative Food and Water Restriction of Laboratory Pigs (Sus scrofa).

The traditionally cited recommendations for the preoperative restriction of food (including bedding) and water in pigs do not appear to be evidence-based. As a preliminary step in elucidating a rationale for and standardizing preoperative food and water restriction (PFWR), this structured review recorded recent reported practices in PFWR in laboratory pigs and its consequences. Medline, Google Scholar and Web of Science databases were searched for recently published (2012 - 2014) recovery surgery procedures in pigs. Information pertaining to PFWR practices, as delineated in the ARRIVE guidelines, was extracted from the 233 articles retrieved. Food withdrawal was described in 73 of the 233 (31%) papers evaluated, bedding withdrawal in 5 articles (2%), and water withholding in 13 publications (6%) papers. Food, bedding, and water withdrawal regimens had a median (range) duration of 12 (4 to 48), 48 (48 to 72), and 12 (2 to 12) h, respectively. Compared with other types of procedures, articles describing gastrointestinal or abdominal surgery were more likely to report fasting regimes. Liquid diets were described in 11 of the 233 (5%) publications evaluated. Adverse effects of PFWR effects were not reported. These data reveal considerable variation in PFWR practices. The stress of fasting coupled with the absence of evidence for current recommendations makes the rationale and standards for PFWR in pigs worthy of further study.

Modulation of spinal shape with growth following implantation of a novel surgical implant.

PURPOSE: First, to determine whether scoliosis development could be limited or reversed by growth when a novel modular hinged implant was fixed to the convexity of a scoliosis created by contralateral rib and laminar tethering and unilateral rib resection in a sheep model. Second, to assess the effect and performance of the implant in normal non-tethered sheep. METHODS: At 5 weeks, 20 Scottish Blackface lambs underwent surgery to create a right sided scoliosis by (i) tethering the left lamina of T5-L1 and the left lower six ribs and (ii) resecting a segment of their right lower six ribs [1, 2]. Twelve weeks later, through an antero-lateral thoracotomy, a mobile bi-planar hinged implant was inserted onto the right side of the spine of eight animals (group 1). For comparison, 12 sheep were tethered only but had no implant insertion (group 2). In addition, seven had no tethering but were implanted (group 3) and normal growth patterns were observed in five that had no surgery (group 4). Curve progression was assessed by plain radiography and CT over a 1-year period. RESULTS: Before implant insertion the trial animals had a scoliosis of 35º ± 16º and a lordosis of 44º ± 20º (n = 8, mean ± SD). Surgery immediately reduced these values to 25º ± 14º, p < 0.01 and 35º ± 18º, p < 0.001, with scoliosis continuing to decrease during the next three months. Spinal flexibility was retained. In the un-tethered sheep, a scoliosis of 10º ± 6º was created on the opposite side to the implant (p < 0.05) with no significant change in alignment in the sagittal plane (1º ± 6º). The implant did not cause any adverse effect on growth or affect neurological function. CONCLUSIONS: In the un-tethered animals the effect of the implant was to create a scoliotic deformity and in the tethered to improve deformity while maintaining spinal motion. We believe that the results are promising and that devices of similar construct may be of use in children with scoliosis, potentially changing current methods of clinical care.

Creation of an ovine model of progressive structural lordo-scoliosis using a unilateral laminar tether.

PURPOSE: To characterise changes in vertebral dimension in an ovine model of scoliosis and determine whether a reproducible curvature could be created that would be suitable for future testing of curve modifying surgical implants. METHODS: At a mean age of 5 weeks, 28 Scottish blackface sheep were anaesthetised. A 4 mm braided synthetic tape was laid under the left lamina of T5 and L1 and tightened to 'hand' tension. A scoliosis was then created by binding the six lowest ribs on the same side just distal to their rib angles and resecting a segment from each of the opposite ribs. Radiographs were taken at 4 weekly intervals, and CT images at 2, 5 and 7 months post tethering, to determine multi-planar curve progression. 20 animals were assessed at age 3 months, 12 at 41 weeks and 10 at 1 year with comparisons to five control animals. RESULTS: A significant bi-planar deformity was produced in all animals (scoliosis 32 ± 13º and lordosis 53 ± 21º 2 months post tethering; mean ± SD, n = 22). During the next 5 months the scoliosis decreased slightly (p = 0.08) but the sagittal deformity remained static: 21 ± 18° and 53 ± 19°, respectively (n = 12). The values at 7 months were associated with a mean 6 ± 4º rotational deformity. There was approximately twice as much growth in the right anterior aspects of the apical vertebrae as in the left posterior. CONCLUSIONS: With appropriate care it was possible to obtain a reproducible curvature in immature sheep. The methods described are suitable for use in studies of growth modulation and other spinal devices.

Electrocardiographic indicators of excitability in horses for predicting recovery quality after general anaesthesia.

OBJECTIVE: To determine whether preoperative electrocardiographic measurements linked to sympathetic nervous activity could be used to predict recovery quality after general anaesthesia in horses. STUDY DESIGN: Prospective, clinical study. ANIMALS: Eighteen adult client-owned horses. METHODS: The electrocardiogram (ECG) was recorded presurgery in horses under three standard conditions: stabled unattended; with a groom whilst being led along a standard course; alone in the induction box. After surgery, each animal's recovery quality was scored by eight experienced anaesthetists or technicians using Donaldson's scoring system (2000). The digitized ECG recordings were analyzed for T-wave morphology, mean heart rate (HR), HR variability (HRV) and HRV derivatives including mean R-R interval, standard deviation of normal intervals (SDNN) and the root mean square of successive intervals (RMSSD), low (LF) and high frequency (HF) activity and the LF/HF ratio in both fast Fourier transformed and autoregressive spectra. Correlations between ECG variables and recovery score were examined using Spearman's rank correlation. RESULTS: There was no significant correlation between preanaesthetic ECG measurements and recovery quality. CONCLUSIONS: Predictions of recovery quality after general anaesthesia in horses cannot be based on preanaesthetic ECG variables. CLINICAL RELEVANCE: Measures other than those based on the ECG should be investigated as predictors of recovery quality.

The perioperative care of lambs and ewes when the former undergo major experimental (scoliotic) surgery.

The purpose of the study was to optimize postoperative comfort in lambs anaesthetized for the surgical creation of scoliosis while maintaining the ewe-lamb relationship to miminize rejection rates. The first management plan produced six scoliotic lambs but intraoperative hypoventilation and hypovolaemia followed by postoperative dyspnoea, pain, monitoring and nursing difficulties, hypothermia, hypoglycaemia and tympany were encountered. Three of eight lambs (38%) were rejected by their ewes. Perioperative management was amended which, combined with improved surgical technique, produced 16 scoliotic lambs. The lambs recovered more rapidly (mean time to standing after discontinuation of anaesthesia was reduced from 12 h to 70 min) and appeared to be more comfortable. No rejections occurred after the refinements were implemented.