Validation of three-dimensional thoracic electrical impedance tomography of horses during normal and increased tidal volumes.

Objective. Data from two-plane electrical impedance tomography (EIT) can be reconstructed into various slices of functional lung images, allowing for more complete visualisation and assessment of lung physiology in health and disease. The aim of this study was to confirm the ability of 3D EIT to visualise normal lung anatomy and physiology at rest and during increased ventilation (represented by rebreathing).Approach. Two-plane EIT data, using two electrode planes 20 cm apart, were collected in 20 standing sedate horses at baseline (resting) conditions, and during rebreathing. EIT data were reconstructed into 3D EIT whereby tidal impedance variation (TIV), ventilated area, and right-left and ventral-dorsal centres of ventilation (CoVRLand CoVVD, respectively) were calculated in cranial, middle and caudal slices of lung, from data collected using the two planes of electrodes.Main results. There was a significant interaction of time and slice for TIV (p< 0.0001) with TIV increasing during rebreathing in both caudal and middle slices. The ratio of right to left ventilated area was higher in the cranial slice, in comparison to the caudal slice (p= 0.0002). There were significant effects of time and slice on CoVVDwhereby the cranial slice was more ventrally distributed than the caudal slice (p< 0.0009 for the interaction).Significance. The distribution of ventilation in the three slices corresponds with topographical anatomy of the equine lung. This study confirms that 3D EIT can accurately represent lung anatomy and changes in ventilation distribution during rebreathing in standing sedate horses.

Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled before hemorrhage and then 2, 4, and 6 h later. Following hemorrhage and RBC transfusion, free iron increased in all dogs over time (both p < 0.001). Inflammation biomarkers interleukin-6 (IL6), CXC motif chemokine-8 (CXCL8), interleukin-10 (IL10), and keratinocyte-derived chemokine (KC) increased in all dogs over time (all p < 0.001). Logarithmic growth of E. coli clones within blood collected 6 h post-transfusion was not different between groups. Only total iron-binding capacity was different between groups over time, being significantly increased in the deferoxamine group at 2 and 4 h post-transfusion (both p < 0.001). In summary, while free iron and inflammation biomarkers increased post-RBC transfusion, deferoxamine administration did not impact circulating free iron, inflammation biomarkers, or in vitro growth of E. coli when compared with placebo.

Thoracic electrical impedance tomography identifies heterogeneity in lungs associated with respiratory disease in cattle. A pilot study.

Respiratory disease in cattle is a significant global concern, yet current diagnostic methods are limited, and there is a lack of crush-side tests for detecting active disease. To address this gap, we propose utilizing electrical impedance tomography (EIT), a non-invasive imaging technique that provides real-time visualization of lung ventilation dynamics. The study included adult cattle from farms in Western Australia. The cattle were restrained in a crush. A standardized respiratory scoring system, which combined visual, auscultation, and clinical scores, was conducted by two non-conferring clinicians for each animal. The scores were blinded and averaged. During assessment, an EIT electrode belt was placed around the thorax. EIT recordings of ten suitable breaths were taken for analysis before the cattle were released back to the herd. Based on the combined examination scoring, the cattle were categorized as having healthy or diseased lungs. To allow visual interpretation of each breath and enable the creation of the quartile ventilation ratio (VQR), Flow/Tidal Impedance Variation curves (F/TIV) were generated for each breath. The analysis focused on two EIT variables: The novel VQR over time during inhalation and exhalation and global expiratory impedance (TIVEXP) adjusted by breath length. A mixed effects model was used to compare these variables between healthy and diseased cattle. Ten adult cattle of mixed ages were used in the current analysis. Five cattle were scored as healthy and five as diseased. There was a significant difference in the examination scores between the healthy and diseased group (P = 0.03). A significant difference in VQR during inhalation (P = 0.03) was observed between the healthy and diseased groups. No difference was seen in VQR over time during exhalation (P = 0.3). The TIVEXP was not different between groups (P = 0.36). In this study, EIT was able to detect differences in inhalation mechanics when comparing healthy and diseased cattle as defined via clinical examination, highlighting the clinical utility of EIT.

Biomarkers of Coagulation and Inflammation in Dogs after Randomized Administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann's Solution.

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES.

Performance evaluation of electrode design and material for a large animal electrical impedance tomography belt.

BACKGROUND: Electrical impedance tomography (EIT) produces lung ventilation images via a thoracic electrode belt. Robust electrode design and material, providing low electrode skin contact impedance (SCI), is needed in veterinary medicine. The aim of this study was to compare three EIT electrode designs and materials. METHODS: Simulations of cylindrical, rectangular and spiked electrode designs were used to evaluate electrode SCI as a function of electrode size, where skin contact was uneven. Gold-plated washers (EGW ), zinc-plated rivets (EZR ) and zinc-galvanised spikes (EZS ) were assigned randomly on two interconnected EIT belts. Gel was applied to the cranial or caudal belt and placed on 17 standing cattle. SCI was recorded at baseline and 3, 5, 7, 9 and 11 minutes later. RESULTS: Simulations that involved electrodes with a greater skin contact area had lower and more uniform SCI. In cattle, SCI decreased with all electrodes over time (p < 0.01). Without gel, no difference was found between EGW and EZS , while SCI was higher for EZR (p < 0.03). With gel, SCI was lower in EGW and EZR (p < 0.026), with the SCI in EGW being the lowest (p < 0.01). LIMITATIONS: Low numbers of animals and static electrode position may affect SCI. CONCLUSIONS: Electrode design is important for EIT measurement, with larger electrode designs able to compensate for the use of less conductive materials. Gel is not necessary to achieve acceptable SCI in large animals.

Thoracic Electrical Impedance Tomography-The 2022 Veterinary Consensus Statement.

Electrical impedance tomography (EIT) is a non-invasive real-time non-ionising imaging modality that has many applications. Since the first recorded use in 1978, the technology has become more widely used especially in human adult and neonatal critical care monitoring. Recently, there has been an increase in research on thoracic EIT in veterinary medicine. Real-time imaging of the thorax allows evaluation of ventilation distribution in anesthetised and conscious animals. As the technology becomes recognised in the veterinary community there is a need to standardize approaches to data collection, analysis, interpretation and nomenclature, ensuring comparison and repeatability between researchers and studies. A group of nineteen veterinarians and two biomedical engineers experienced in veterinary EIT were consulted and contributed to the preparation of this statement. The aim of this consensus is to provide an introduction to this imaging modality, to highlight clinical relevance and to include recommendations on how to effectively use thoracic EIT in veterinary species. Based on this, the consensus statement aims to address the need for a streamlined approach to veterinary thoracic EIT and includes: an introduction to the use of EIT in veterinary species, the technical background to creation of the functional images, a consensus from all contributing authors on the practical application and use of the technology, descriptions and interpretation of current available variables including appropriate statistical analysis, nomenclature recommended for consistency and future developments in thoracic EIT. The information provided in this consensus statement may benefit researchers and clinicians working within the field of veterinary thoracic EIT. We endeavor to inform future users of the benefits of this imaging modality and provide opportunities to further explore applications of this technology with regards to perfusion imaging and pathology diagnosis.

Comparison of Effects of an Endotracheal Tube or Facemask on Breathing Pattern and Distribution of Ventilation in Anesthetized Horses.

Equine respiratory physiology might be influenced by the presence of an endotracheal tube (ETT). This experimental, randomized cross-over study aimed to compare breathing pattern (BrP) and ventilation distribution in anesthetized horses spontaneously breathing room air via ETT or facemask (MASK). Six healthy adult horses were anesthetized with total intravenous anesthesia (TIVA; xylazine, ketamine, guaiphenesin), breathing spontaneously in right lateral recumbency, and randomly assigned to ETT or MASK for 30 min, followed by the other treatment for an additional 30 min. During a second anesthesia 1 month later, the treatment order was inversed. Electrical impedance tomography (EIT) using a thoracic electrode belt, spirometry, volumetric capnography, esophageal pressure difference (ΔPoes), venous admixture, and laryngoscopy data were recorded over 2 min every 15 min. Breaths were classified as normal or alternate (sigh or crown-like) according to the EIT impedance curve. A mixed linear model was used to test the effect of treatment on continuous outcomes. Cochran-Mantel-Haenszel analysis was used to test for associations between global BrP and treatment. Global BrP was associated with treatment (p = 0.012) with more alternate breaths during ETT. The center of ventilation right-to-left (CoVRL) showed more ventilation in the non-dependent lung during ETT (p = 0.025). The I:E ratio (p = 0.017) and ΔPoes (p < 0.001) were smaller, and peak expiratory flow (p = 0.009) and physiologic dead space (p = 0.034) were larger with ETT. The presence of an ETT alters BrP and shifts ventilation toward the non-dependent lung in spontaneously breathing horses anesthetized with TIVA.

Cannula cricothyroidotomy in the impalpable neck: An observational study of simulated 'can't intubate, can't oxygenate' scenarios by teams following a cannula-first algorithm in live anaesthetised pigs.

Live animal models can be used to train anaesthetists to perform emergency front-of-neck-access. Cannula cricothyroidotomy success reported in previous wet lab studies contradicts human clinical data. This prospective, observational study reports success of a cannula-first 'can't intubate, can't oxygenate' algorithm for impalpable anatomy during high fidelity team simulations using live, anaesthetised pigs.Forty-two trained anaesthesia teams were instructed to follow the Royal Perth Hospital can't intubate, can't oxygenate algorithm to re-oxygenate a desaturating pig with impalpable neck anatomy (mean (standard deviation, SD) 16.2 (3.5) kg); mean (SD) tracheal internal diameter 11 (1.4) mm. Teams were informed that failure would prompt veterinary-led euthanasia.All teams performed percutaneous cannula cricothyroidotomy as the initial technique, with a median (interquartile range, IQR (range)) start time of 42 (35-50 (24-93)) s. First-pass percutaneous cannula success was 29% to both insufflate tracheal oxygen and re-oxygenate. Insufflation success improved with repeated percutaneous attempts (up to three), but prolonged hypoxia time increasingly necessitated euthanasia (insufflation 57%; re-oxygenation 48%). First, second and third percutaneous attempts achieved insufflation at median (IQR (range)) 74 (64-91 (46-110)) s, 111 (95-136 (79-150)) s and 141 (127-159 (122-179)) s, respectively. Eighteen teams failed with percutaneous cannulae and performed scalpel techniques, predominantly dissection cannulation (n = 17) which achieved insufflation in all cases (insufflation 100%; re-oxygenation 47%). Scalpel attempts were started at median (IQR (range)) 142 (133-218 (97-293)) s and achieved insufflation at 232 (205-303 (152-344)) s.While percutaneous cannula cricothyroidotomy could rapidly re-oxygenate, the success rate was low and teams repeated attempts beyond the recommended 60 s time frame, delaying transition to the more successful dissection cannula technique. We recommend this 'cannula-first' can't intubate, can't oxygenate algorithm adopts a 'single best effort' strategy for percutaneous cannula, with failure prompting a scalpel technique.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Determination of tidal volume by electrical impedance tomography (EIT) after indirect two-point calibration.

Objective. A linear relationship between impedance change (ΔZ) measured by thoracic electrical impedance tomography (EIT) and tidal volume (VT) has been demonstrated. This study evaluated the agreement between the displayed VT calculated by the EIT software (VTEIT) and spirometry (VTSPIRO) after an indirect two-point calibration.Approach.The EIT software was programmed to execute a bedside two-point calibration from the subject-specific, linear equation defining the relationship between ΔZand VTSPIROand displaying VTEITbreath-by-breath in 20 neutered male, juvenile pigs. After EIT calibration VTs of 8, 12, 16 and 20 ml kg-1were applied to the lungs. VTEITand VTSPIROwere recorded and analysed using Bland-Altman plot for multiple subject measurements. Volumetric capnography (VCap) and spirometry data were explored as components of variance using multiple regression.Main results.A mean relative difference (bias) of 0.7% with 95% confidence interval (CI) of -10.4% to 10.7% were found between VTEITand VTSPIROfor the analysed data set. The variance in VTEITcould not be explained by any of the measured VCap or spirometry variables.Significance.The narrow CI estimated in this study allows the conclusion that EIT and its software can be used to measure and accurately convert ΔZinto mililitre VT at the bedside after applying an indirect two-point calibration.

Electrical impedance tomography to measure lung ventilation distribution in healthy horses and horses with left-sided cardiac volume overload.

BACKGROUND: Left-sided cardiac volume overload (LCVO) can cause fluid accumulation in lung tissue changing the distribution of ventilation, which can be evaluated by electrical impedance tomography (EIT). OBJECTIVES: To describe and compare EIT variables in horses with naturally occurring compensated and decompensated LCVO and compare them to a healthy cohort. ANIMALS: Fourteen adult horses, including university teaching horses and clinical cases (healthy: 8; LCVO: 4 compensated, 2 decompensated). METHODS: In this prospective cohort study, EIT was used in standing, unsedated horses and analyzed for conventional variables, ventilated right (VAR) and left (VAL) lung area, linear-plane distribution variables (avg-max VΔZLine , VΔZLine ), global peak flows, inhomogeneity factor, and estimated tidal volume. Horses with decompensated LCVO were assessed before and after administration of furosemide. Variables for healthy and LCVO-affected horses were compared using a Mann-Whitney test or unpaired t-test and observations from compensated and decompensated horses are reported. RESULTS: Compared to the healthy horses, the LCVO cohort had significantly less VAL (mean difference 3.02; 95% confidence interval .77-5.2; P = .02), more VAR (-1.13; -2.18 to -.08; P = .04), smaller avg-max VΔZLLine (2.54; 1.07-4.00; P = .003) and VΔZLLine (median difference 5.40; 1.71-9.09; P = .01). Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide. CONCLUSIONS AND CLINICAL IMPORTANCE: EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses.

Improved Cardiovascular Tolerance to Hemorrhage after Oral Resveratrol Pretreatment in Dogs.

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs' blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.

Analytical validation and reference intervals for a commercial multiplex assay to measure five novel biomarkers for acute kidney injury in canine urine.

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration. The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/- 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20-22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).

Use of Electrical Impedance Tomography (EIT) to Estimate Tidal Volume in Anaesthetized Horses Undergoing Elective Surgery.

This study explores the application of electric impedance tomography (EIT) to estimate tidal volume (VT) by measuring impedance change per breath (∆Zbreath). Seventeen healthy horses were anaesthetised and mechanically ventilated for elective procedures requiring dorsal recumbency. Spirometric VT (VTSPIRO) and ∆Zbreath were recorded periodically; up to six times throughout anaesthesia. Part 1 assessed these variables at incremental delivered VT of 10, 12 and 15 mL/kg. Part 2 estimated VT (VTEIT) in litres from ∆Zbreath at three additional measurement points using a line of best fit obtained from Part 1. During part 2, VT was adjusted to maintain end-tidal carbon dioxide between 45-55 mmHg. Linear regression determined the correlation between VTSPIRO and ∆Zbreath (part 1). Estimated VTEIT was assessed for agreement with measured VTSPIRO using Bland Altman analysis (part 2). Marked variability in slope and intercepts was observed across horses. Strong positive correlation between ∆Zbreath and VTSPIRO was found in each horse (R2 0.9-0.99). The agreement between VTEIT and VTSPIRO was good with bias (LOA) of 0.26 (-0.36-0.88) L. These results suggest that, in anaesthetised horses, EIT can be used to monitor and estimate VT after establishing the individual relationship between these variables.

Can bronchoconstriction and bronchodilatation in horses be detected using electrical impedance tomography?

BACKGROUND: Electrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in horses. OBJECTIVES: To confirm that EIT can detect histamine-provoked changes in airflow and subsequent drug-induced bronchodilatation. Novel EIT flow variables were developed and examined for changes in airflow. METHODS: Bronchoconstriction was induced using stepwise histamine bronchoprovocation in 17 healthy sedated horses. The EIT variables were recorded at baseline, after saline nebulization (control), at the histamine concentration causing bronchoconstriction (Cmax ) and 2 and 10 minutes after albuterol (salbutamol) administration. Peak global inspiratory (PIFEIT ) and peak expiratory EIT (PEFEIT ) flow, slope of the global expiratory flow-volume curve (FVslope ), steepest FVslope over all pixels in the lung field, total impedance change (surrogate for tidal volume; VTEIT ) and intercept on the expiratory FV curve normalized to VTEIT (FVintercept /VTEIT ) were indexed to baseline and analyzed for a difference from the control, at Cmax , 2 and 10 minutes after albuterol. Multiple linear regression explored the explanation of the variance of Δflow, a validated variable to evaluate bronchoconstriction using all EIT variables. RESULTS: At Cmax , PIFEIT , PEFEIT , and FVslope significantly increased whereas FVintercept /VT decreased. All variables returned to baseline 10 minutes after albuterol. The VTEIT did not change. Multivariable investigation suggested 51% of Δflow variance was explained by a combination of PIFEIT and PEFEIT . CONCLUSIONS AND CLINICAL IMPORTANCE: Changes in airflow during histamine challenge and subsequent albuterol administration could be detected by various EIT flow volume variables.

Comparison of pulmonary function in isoflurane anaesthetized ventilated sheep (Ovis aries) following administration of intravenous xylazine versus medetomidine.

Alpha2 receptor agonists (alpha2-agonists) are useful sedative and analgesic agents in sheep, but have adverse pulmonary effects, which are reportedly similar between different alpha2-agonists. This randomized crossover study compared pulmonary function after intravenous administration of an alpha2-agonist, either xylazine or an equipotent dose of medetomidine in 34 female sheep anaesthetized twice. Pulmonary function was assessed using spirometry, volumetric capnography, arterial blood gas analysis 1 min prior to, and 5 and 10 min after administration of the allocated alpha 2 agonist drug. Pulmonary structural changes were subsequently assessed using computed tomography (CT). Tachypnoea or hypoxaemia prompted reversal with atipamezole and exclusion of data. Data were analysed for a fixed effect of drug using a mixed effect linear model with significance set at p < 0.05. Ten sheep administered xylazine required atipamezole while none of sheep receiving medetomidine did. Xylazine produced significantly higher respiratory frequency, airway pressures, airway resistance and arterial carbon dioxide (CO2), and lower dynamic compliance, tidal volume, CO2 elimination and end tidal CO2 tension and arterial oxygen tension than medetomidine. This was associated with a significantly lower % of aerated tissue and higher % poorly and non-aerated tissue in CT images of sheep receiving xylazine versus medetomidine. In conclusion, xylazine administration produced marked decreases in pulmonary function, in ventilated isoflurane anaesthetized sheep, when compared to an equipotent dose of medetomidine when administered as an intravenous bolus supporting the use of medetomidine when alpha2-agonists are required.

Prospective randomized controlled blinded clinical trial evaluating biomarkers of acute kidney injury following 6% hydroxyethyl starch 130/0.4 or Hartmann's solution in dogs.

OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 130/0.4, compared with a Hartmann's solution control (CRYST), on urine biomarkers of acute kidney injury (AKI) in dogs prescribed a fluid bolus. DESIGN: Randomized, controlled, blinded clinical trial January 2018 to February 2019. SETTING: University teaching hospital. ANIMALS: Forty client-owned dogs. INTERVENTIONS: Dogs prescribed a fluid bolus were randomized to receive at least 10 mL/kg of HES or CRYST with clinicians and investigators blinded to fluid type. Study fluid was used for further boluses as required in the following 24 hours, to a limit of 40 mL/kg total, after which fluid administration was open-label. MEASUREMENTS AND MAIN RESULTS: Urine was collected prior to and 6, 12, and 24 hours after the first study fluid bolus. Urine concentrations of AKI biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM), clusterin, and osteopontin were measured using a magnetic bead multiplexed assay. Osmolality-indexed biomarker concentrations were compared between groups over time with linear mixed-effects models, with P < 0.05 considered significant. The mean volume of study fluid administered was not significantly different between groups (HES: 23.1 mL/kg, CRYST: 25.9 mL/kg; P = 0.47, t-test). There were no significant differences between groups in change over time of osmolality-indexed urine concentrations of NGAL (P = 0.91), cystatin C (P = 0.95), KIM (P = 0.77), clusterin (P = 0.63), or osteopontin (P = 0.91). The maximum Veterinary Acute Kidney Injury (VAKI) score up to 7 days during hospitalization (P = 1.0) and in-hospital mortality (P = 0.49) were not significantly different between groups, as compared by Fisher's exact test. CONCLUSIONS: There were no differences in change over time of urine AKI biomarkers in dogs treated with 10 - 40 mL/kg HES or CRYST over 24 hours. Larger clinical trials with patient-centered outcomes are required to investigate the safety of HES in dogs.

Ability of different assay platforms to measure renal biomarker concentrations during ischaemia-reperfusion acute kidney injury in dogs.

Several protein biomarkers have been shown to be useful for the early diagnosis of acute kidney injury (AKI) in animals and people. Multiplex assays for measurement of a panel of renal biomarkers in canine samples have recently become available. This study compared the use of two such assays, versus previously validated ELISAs, to measure five biomarkers in canine samples during ischaemia-reperfusion (IR) AKI. Blood and urine was collected from six male anaesthetised greyhounds that underwent 1-h of renal ischaemia (severe hypotension induced by acute haemorrhage) and 2-h of reperfusion (intravenous fluid resuscitation). Histology confirmed presence of acute tubular injury at 2 h of reperfusion. Concentrations of clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin (NGAL) at baseline and following IR, measured by two different multiplex assays and previously-validated single analyte immunoassays, were compared. Only NGAL was significantly elevated following IR with all assays investigated. Whether concentrations of the other four biomarkers were significantly increased following IR depended on the assay used. Concentrations of cystatin C and KIM-1 measured with the multiplex assays were of a vast magnitude lower than those measured with the corresponding single analyte ELISAs. We conclude that further validation is required before these assays can reliably be used to measure AKI biomarkers in canine samples.

Corrigendum: Hypocoagulability and Platelet Dysfunction Are Exacerbated by Synthetic Colloids in a Canine Hemorrhagic Shock Model.

[This corrects the article DOI: 10.3389/fvets.2018.00279.].

Validation of a commercial magnetic bead-based multiplex assay for 5 novel biomarkers of acute kidney injury in canine serum.

Interest is growing in measurement of novel biomarkers for the diagnosis of acute kidney injury. Multiplex assays may provide a rapid and cost-effective way of measurement; however, sparse information is published regarding their use in dogs. We aimed to validate a commercial magnetic bead-based assay for 5 biomarkers: clusterin (Clus), cystatin C (CysC), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Intra- and inter-assay imprecision, linearity under dilution (LUD), spike recovery (S-R), and hemoglobin interference were evaluated using serum from healthy and diseased dogs. Additionally, the effect of sample type (serum vs. plasma) was investigated. All values for Clus and MCP-1 were outside the assay's measurable range. Intra- and inter-assay precision were acceptable for NGAL (CVs 8.8% and 13.2%, respectively). Regression analysis of LUD and S-R indicated good linearity for CysC and NGAL. Hemolysis did not affect measurement of any biomarker. Measured concentrations of CysC (p = 0.018) and NGAL (p = 0.015) were significantly lower in sodium citrate plasma compared to serum. We conclude that this magnetic bead-based assay is precise and accurate for NGAL measurement in canine serum. Inappropriate standards for MCP-1 and Clus, and poor accuracy for KIM-1 measurement, suggest that this assay cannot reliably quantify those biomarkers in canine blood. Measurements of CysC in canine blood using this assay must be interpreted with caution given inter-assay imprecision.