Publications by authors named "David Bardell"

13 Publications

  • Page 1 of 1

miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging.

Aging Cell 2021 Oct 24;20(10):e13475. Epub 2021 Sep 24.

Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Satellite cell-dependent skeletal muscle regeneration declines during aging. Disruptions within the satellite cells and their niche, together with alterations in the myofibrillar environment, contribute to age-related dysfunction and defective muscle regeneration. In this study, we demonstrated an age-related decline in satellite cell viability and myogenic potential and an increase in ROS and cellular senescence. We detected a transient upregulation of miR-24 in regenerating muscle from adult mice and downregulation of miR-24 during muscle regeneration in old mice. FACS-sorted satellite cells were characterized by decreased levels of miR-24 and a concomitant increase in expression of its target: Prdx6. Using GFP reporter constructs, we demonstrated that miR-24 directly binds to its predicted site within Prdx6 mRNA. Subtle changes in Prdx6 levels following changes in miR-24 expression indicate miR-24 plays a role in fine-tuning Prdx6 expression. Changes in miR-24 and Prdx6 levels were associated with altered mitochondrial ROS generation, increase in the DNA damage marker: phosphorylated-H2Ax and changes in viability, senescence, and myogenic potential of myogenic progenitors from mice and humans. The effects of miR-24 were more pronounced in myogenic progenitors from old mice, suggesting a context-dependent role of miR-24 in these cells, with miR-24 downregulation likely a part of a compensatory response to declining satellite cell function during aging. We propose that downregulation of miR-24 and subsequent upregulation of Prdx6 in muscle of old mice following injury are an adaptive response to aging, to maintain satellite cell viability and myogenic potential through regulation of mitochondrial ROS and DNA damage pathways.
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October 2021

Epidural administration of opioid analgesics improves quality of recovery in horses anaesthetised for treatment of hindlimb synovial sepsis.

Equine Vet J 2021 Jul 23;53(4):682-689. Epub 2020 Sep 23.

Institute of Veterinary Science, University of Liverpool, Neston, UK.

Background: Opioid epidural analgesia has been shown to provide effective analgesia in horses. There is a lack of evidence regarding the effect of opioid epidural analgesia on quality of recovery in horses.

Objectives: Identify whether opioid epidural analgesia influences quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis.

Study Design: Single-centre retrospective cross-sectional study.

Methods: Data were obtained from the clinical records of horses which had undergone arthroscopic or tenoscopic surgery for management of hindlimb synovial sepsis over a 9-year period in a referral hospital population. Multivariable logistic regression analysis was used to identify the perioperative factors that impact on quality of recovery.

Results: Records from 149 horses, undergoing 170 general anaesthetics were included. Multivariable logistic regression analysis showed that opioid epidural analgesia (OR 3.0, 95% CI 1.2 to 7.2, P = .02) was associated with good quality of recovery, whereas Cob breeds (OR 0.16, 95% CI 0.06 to 0.46, P = .001), age (in years) (OR 0.90, 95% CI 0.83 to 0.97, P = .004) increasing intraoperative dosages (in mg/kg) of thiopental (OR 0.64, 95% CI 0.46 to 0.90, P = .01) or ketamine (OR 0.42, 95% CI 0.18 to 0.98, P = .04) were associated with poor quality of recovery.

Main Limitations: Certain variables that may influence quality of recovery, such as patient temperament and hindlimb orthopaedic co-morbidities were not recorded. The clinical prediction model obtained is only applicable to the specific facilities, population and perianaesthetic management practiced at our institution.

Conclusions: Opioid epidural analgesia is significantly associated with good quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis. Other risk factors, such as increasing age, cob breed, use of higher intraoperative dosages (in mg/kg) of ketamine and/or thiopental, were associated with poor quality of recovery.
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July 2021

Epigenetic mechanisms in Tendon Ageing.

Br Med Bull 2020 10;135(1):90-107

Department of Musculoskeletal Biology, Institute of Life Course and Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, UK.

Introduction: Tendon is a composite material with a well-ordered hierarchical structure exhibiting viscoelastic properties designed to transfer force. It is recognized that the incidence of tendon injury increases with age, suggesting a deterioration in homeostatic mechanisms or reparative processes. This review summarizes epigenetic mechanisms identified in ageing healthy tendon.

Sources Of Data: We searched multiple databases to produce a systematic review on the role of epigenetic mechanisms in tendon ageing.

Areas Of Agreement: Epigenetic mechanisms are important in predisposing ageing tendon to injury.

Areas Of Controversy: The relative importance of epigenetic mechanisms are unknown in terms of promoting healthy ageing. It is also unknown whether these changes represent protective mechanisms to function or predispose to pathology.

Growing Point: Epigenetic markers in ageing tendon, which are under-researched including genome-wide chromatin accessibility, should be investigated.

Areas Timely For Developing Research: Metanalysis through integration of multiple datasets and platforms will enable a holistic understanding of the epigenome in ageing and its relevance to disease.
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October 2020

Determination of reference intervals for equine arterial blood-gas, acid-base and electrolyte analysis.

Vet Anaesth Analg 2019 Nov 14;46(6):765-771. Epub 2019 Jun 14.

Institute of Veterinary Science, University of Liverpool, Wirral, UK; Institute of Ageing and Chronic Disease, Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK.

Objective: To establish reference intervals for arterial blood-gas (ABG), acid-base and electrolyte values from a healthy equine population.

Study Design: Retrospective clinical study.

Animals: A total of 139 client-owned, systemically healthy horses, 1 year of age and older, presented for elective surgical procedures.

Methods: Blood samples were collected anaerobically from the transverse facial or common carotid artery of horses breathing room air, prior to administration of preanaesthetic medication. Samples were analysed immediately, without correction for body temperature, using an automated bench-top analyser. Variables analysed included pH, arterial partial pressure of carbon dioxide (PaCO) and arterial partial pressure of oxygen (PaO) and plasma concentrations of sodium (Na), potassium (K), calcium (Ca) and chloride (Cl). Actual and standardized plasma bicarbonate concentration [HCO (P) and HCO (P, st)], blood and extracellular fluid base excess [base (B) and base (ECF)] and anion gap (AG) were calculated by the machine from preprogrammed algorithms. Methods used for determination of PaCO, PaO, HCO (P), HCO (P, st), base (B) and base (ECF) met the guidelines of the Clinical and Laboratory Standards Institute. Reference intervals were determined with the nonparametric or the standard parametric method dependent on data distribution.

Results: Reference intervals were determined for pH, 7.37-7.49; PaCO, 4.84-7.20 kPa (36.3-54.0 mmHg); PaO, 11.01-14.97 kPa (82.6-112.3 mmHg); Na, 133-141 mmol L; K, 3.05-4.65 mmol L; Ca, 1.34-1.72 mmol L; Cl, 100-110 mmol L; HCO (P), 23.55-33.90 mmol L; HCO (P, st), 23.87-32.45 mmol L; base (B), 0.51-8.80 mmol L; base (ECF), -0.53 to 9.39 mmol L and AG, 1.5-11.5 mEq L.

Conclusions And Clinical Relevance: These data were derived from the largest group of horses reported in a single study and may aid in interpretation of ABG, acid-base and electrolyte measurements in clinical practice.
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November 2019

Corneal abrasion and microbial contamination in horses following general anaesthesia for non-ocular surgery.

Vet Anaesth Analg 2018 May 9;45(3):278-284. Epub 2018 Jan 9.

Phillip Leverhulme Equine Hospital, Institute of Veterinary Science, University of Liverpool, Liverpool, UK; Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.

Objective: To evaluate the incidence of corneal abrasions/ulceration and microbial contamination in horses undergoing general anaesthesia.

Study Design: Prospective, observational, clinical study.

Animals: A total of 40 client-owned healthy horses scheduled for elective non-ophthalmic procedures.

Methods: Conjunctival sac swabs were taken, fluorescein dye applied and digital images recorded from both eyes of the horses after preanaesthetic medication and 24 hours after recovery from general anaesthesia. A paraffin-based bland ophthalmic ointment was applied on the ocular surface intraoperatively following collection of a sample into a sterile container. All samples underwent aerobic, anaerobic and fungal culture. Subject demographics, chronology of ophthalmic ointment use, anaesthesia duration, recumbency after induction, during surgery and recovery, fluorescein uptake and culture results were recorded. Descriptive statistics were performed.

Results: Complete data were collected from 34 horses; six (17.6%) developed mild unilateral generalized fluorescein uptake consistent with corneal abrasions. Recumbency on the operating table was the only risk factor significantly associated with corneal abrasions. A total of 11 bacterial species were identified; Staphylococcus spp. (15 eyes) and Micrococcus spp. (eight eyes) were the most frequently isolated bacteria. Two fungal species were isolated postoperatively (Aspergillus spp., Saccharomyces spp.) in two eyes. Ointment contamination was recorded in two cases (5%) but cross-contamination was not recognized.

Conclusionsand Clinical Relevance: Incidence of corneal abrasion/ulceration in horses undergoing general anaesthesia and contamination rate of ophthalmic solutions are similar to those previously reported in dogs.
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May 2018

Regional ventilation distribution and dead space in anaesthetized horses treated with and without continuous positive airway pressure: novel insights by electrical impedance tomography and volumetric capnography.

Vet Anaesth Analg 2018 Jan 3;45(1):31-40. Epub 2017 Jul 3.

Swisstom AG, Landquart, Switzerland.

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) on regional distribution of ventilation and dead space in anaesthetized horses.

Study Design: Randomized, experimental, crossover study.

Animals: A total of eight healthy adult horses.

Methods: Horses were anaesthetized twice with isoflurane in 50% oxygen and medetomidine as continuous infusion in dorsal recumbency, and administered in random order either CPAP (8 cmHO) or NO CPAP for 3 hours. Electrical impedance tomography (and volumetric capnography (VCap) measurements were performed every 30 minutes. Lung regions with little ventilation [dependent silent spaces (DSSs) and nondependent silent spaces (NSSs)], centre of ventilation (CoV) and dead space variables, as well as venous admixture were calculated. Statistical analysis was performed using multivariate analysis of variance and Pearson correlation.

Results: Data from six horses were statistically analysed. In CPAP, the CoV shifted to dependent parts of the lungs (p < 0.001) and DSSs were significantly smaller (p < 0.001), while no difference was seen in NSSs. Venous admixture was significantly correlated with DSS with the treatment time taken as covariate (p < 0.0001; r = 0.65). No differences were found for any VCap parameters.

Conclusions And Clinical Relevance: In dorsally recumbent anaesthetized horses, CPAP of 8 cmHO results in redistribution of ventilation towards the dependent lung regions, thereby improving ventilation-perfusion matching. This improvement was not associated with an increase in dead space indicative for a lack in distension of the airways or impairment of alveolar perfusion.
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January 2018

Evaluation of a new handheld point-of-care blood gas analyser using 100 equine blood samples.

Vet Anaesth Analg 2017 01 22;44(1):77-85. Epub 2017 Feb 22.

School of Veterinary Science, Leahurst Campus, University of Liverpool, Neston, UK.

Objectives: To determine whether the Enterprise point-of-care blood analysis system (EPOC) produces results in agreement with two other blood gas analysers in regular clinical use (i-STAT and Radiometer ABL77) and to investigate the precision of the new machine when used with equine whole blood.

Study Design: Prospective, randomized, non-blinded, comparative laboratory analyser study.

Animals: Horses admitted to a university teaching hospital requiring arterial or venous blood gas analysis as part of their routine clinical management.

Methods: One hundred equine blood samples were run immediately, consecutively and in randomized order on three blood gas analysers. Results of variables common to all three analysers were tested for agreement and compared with guidelines used in human medicine. These require 80% of results from the test analyser to fall within a defined range or percentage of results from the comparator devices to achieve acceptability. Additionally, 21 samples were run twice in quick succession on the EPOC analyser to investigate precision.

Results: Agreement targets were not met for haematocrit, haemoglobin and base excess for either i-STAT or ABL77 analysers. EPOC precision targets were not met for partial pressure of carbon dioxide, ionized calcium, haematocrit and haemoglobin. Overall comparative performance of the EPOC was good to excellent for pH, oxygen tension, potassium, bicarbonate and oxygen saturation of haemoglobin, but marginal to poor for other parameters.

Conclusions And Clinical Relevance: The EPOC may be useful in performing analysis of equine whole blood, but trend analysis of carbon dioxide tension, ionized calcium, haematocrit and haemoglobin should be interpreted with caution. The EPOC should not be used interchangeably with other blood gas analysers.
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January 2017

Regional distribution of ventilation in horses in dorsal recumbency during spontaneous and mechanical ventilation assessed by electrical impedance tomography: a case series.

Vet Anaesth Analg 2017 Jan 23;44(1):127-132. Epub 2017 Feb 23.

Swisstom AG, Landquart, Switzerland.

Objective: To evaluate the regional distribution of ventilation in horses during spontaneous breathing and controlled mechanical ventilation (CMV) using electrical impedance tomography (EIT).

Study Design: Prospective, experimental case series.

Animals: Four anaesthetized experimental horses.

Methods: Horses were anaesthetized with isoflurane in an oxygen-air mixture and medetomidine continuous rate infusion, placed in dorsal recumbency with an EIT belt around the thorax, and allowed to breathe spontaneously until PaCO reached 13.3 kPa (100 mmHg), when volume CMV was started. For each horse, the EIT signal was recorded for at least 2 minutes immediately before (T1), and at 30 (n = 3) or 60 (n = 1) minutes after the start of CMV (T2). The centre of ventilation (CoV), dependent silent spaces (DSS) (likely to represent atelectatic lung areas), non-dependent silent spaces (NSS) (likely to represent lung areas with low ventilation) and total ventilated area (TVA) were evaluated. Cardiac output (CO) was measured and venous admixture and oxygen delivery (DO) were calculated at T1 and T2. Data are presented as median and range.

Results: After the initiation of CMV, the CoV moved ventrally towards the non-dependent lung by 10% [from 57.4% (49.6-60.2%) to 48.3% (41.9-54.4%)]. DSS increased [from 4.1% (0.2-13.9%) to 18.7% (7.5-27.5%)], while NSS [21.7% (9.4-29.2%) to 9.9% (1.0-20.7%)] and TVA [920 (699-1051) to 837 (662-961) pixels] decreased. CO, venous admixture and DO also decreased.

Conclusions And Clinical Relevance: In spontaneously breathing anaesthetized horses in dorsal recumbency, ventilation was essentially centred within the dependent dorsal lung regions and moved towards non-dependent ventral regions as soon as CMV was started. This shows a major lack of ventilation in the dependent lung, which may be indicative of atelectasis.
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January 2017

Horses Auto-Recruit Their Lungs by Inspiratory Breath Holding Following Recovery from General Anaesthesia.

PLoS One 2016 22;11(6):e0158080. Epub 2016 Jun 22.

School of Veterinary Science, University of Liverpool, Liverpool, United Kingdom.

This study evaluated the breathing pattern and distribution of ventilation in horses prior to and following recovery from general anaesthesia using electrical impedance tomography (EIT). Six horses were anaesthetised for 6 hours in dorsal recumbency. Arterial blood gas and EIT measurements were performed 24 hours before (baseline) and 1, 2, 3, 4, 5 and 6 hours after horses stood following anaesthesia. At each time point 4 representative spontaneous breaths were analysed. The percentage of the total breath length during which impedance remained greater than 50% of the maximum inspiratory impedance change (breath holding), the fraction of total tidal ventilation within each of four stacked regions of interest (ROI) (distribution of ventilation) and the filling time and inflation period of seven ROI evenly distributed over the dorso-ventral height of the lungs were calculated. Mixed effects multi-linear regression and linear regression were used and significance was set at p<0.05. All horses demonstrated inspiratory breath holding until 5 hours after standing. No change from baseline was seen for the distribution of ventilation during inspiration. Filling time and inflation period were more rapid and shorter in ventral and slower and longer in most dorsal ROI compared to baseline, respectively. In a mixed effects multi-linear regression, breath holding was significantly correlated with PaCO2 in both the univariate and multivariate regression. Following recovery from anaesthesia, horses showed inspiratory breath holding during which gas redistributed from ventral into dorsal regions of the lungs. This suggests auto-recruitment of lung tissue which would have been dependent and likely atelectic during anaesthesia.
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July 2017

Lack of association between arterial oxygen tensions in horses during exploratory coeliotomy and post-operative incisional complications: A retrospective study.

Vet J 2016 Apr 10;210:24-9. Epub 2015 Nov 10.

School of Veterinary Science, University of Liverpool, Leahurst Campus, Chester High Road, Neston, CH64 7TE, UK.

The aim of this retrospective study was to determine if there was an association between the lowest arterial blood oxygen tensions (PaO2) measured during anaesthesia and post-operative incisional complications in horses. Clinical records of 278 horses undergoing ventral midline coeliotomy from 1 January 2010 to 31 December 2013 were examined. The frequency of incisional complications was 32.0% (n = 89). In a multivariable model, intra-operative arterial blood oxygen tensions (PaO2) were not significantly associated with development of an incisional complication (P = 0.351). Using hypertonic (7.2%) saline (P = 0.028, OR 3.167, 95% CI 1.132-8.861), increasing total plasma protein concentration (TP) (P = 0.002, OR 1.061 per g/L, 95% CI 1.021-1.102), an intestinal resection (P <0.001, OR 4.056, 95% CI 2.231-9.323), increasing body mass (P = 0.004, OR 1.004 per kg, 95% CI 1.001-1.006) and the use of penicillin alone compared with penicillin and gentamicin pre-operatively (P = 0.009, OR 4.145, 95% CI 1.568-10.958) increased the risk of incisional complications. The study was unable to demonstrate a link between low intra-operative PaO2 and increased risk of post-operative incisional complications.
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April 2016

Continuous positive airway pressure (CPAP) decreases pulmonary shunt in anaesthetized horses.

Vet Anaesth Analg 2016 Nov 24;43(6):611-622. Epub 2016 Feb 24.

Division of Anaesthesiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Objective: To evaluate the effects of continuous positive airway pressure (CPAP) on intrapulmonary shunt, cardiac output and oxygen delivery in horses subjected to a 6 hour period of general anaesthesia.

Study Design: Randomized, experimental, crossover study.

Animals: Ten healthy adult horses.

Methods: Following medetomidine, diazepam and ketamine administration, orotracheal intubation was performed and horses positioned in dorsal recumbency. Anaesthesia was maintained with isoflurane carried in an oxygen and air mix (FiO 0.5) combined with a medetomidine infusion. Horses were anaesthetized twice and either CPAP (8 cmH O) or physiologic airway pressure (NO CPAP) was applied to the lungs for 6 hours; the order of treatments was randomly assigned. Following induction of anaesthesia, cardiovascular and respiratory variables (including arterial blood gas analysis) were recorded every 30 minutes, cardiac output was measured every 60 minutes using the lithium dilution technique and oxygen delivery calculated. If PaCO exceeded 100 mmHg (13.3 kPa), controlled ventilation was initiated and horses excluded from further data collection. Groups were compared using a general linear model.

Results: Data from eight horses were analysed. PaO was 15-56 mmHg (2.00-7.45 kPa) higher (p < 0.001) and shunt fraction 6-14% lower (p < 0.001) in the CPAP group. No differences were seen for cardiac output and oxygen delivery. The lack of difference in oxygen delivery was attributed to lower haemoglobin levels in the CPAP group than in the NO CPAP group.

Conclusions And Clinical Relevance: CPAP of 8 cmH O can be used in dorsally recumbent horses to decrease pulmonary shunt fraction without causing a decrease in cardiac output during longterm anaesthesia.
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November 2016

The effect of two different intra-operative end-tidal carbon dioxide tensions on apnoeic duration in the recovery period in horses.

Vet Anaesth Analg 2016 Mar 29;43(2):163-70. Epub 2015 May 29.

Philip Leverhulme Equine Hospital, University of Liverpool, Neston, UK.

Objective: To compare the effect of two different intraoperative end-tidal carbon dioxide tensions on apnoeic duration in the recovery period in horses.

Study Design: Prospective randomized clinical study.

Animals: Eighteen healthy client-owned adult horses (ASA I-II) admitted for elective surgery. Horses were of a median body mass of 595 (238-706) kg and a mean age of 9 ± 5 years.

Methods: A standardized anaesthetic protocol was used. Horses were positioned in dorsal recumbency and randomly allocated to one of two groups. Controlled mechanical ventilation (CMV) was adjusted to maintain the end-tidal carbon dioxide tension (Pe'CO2 ) at 40 ± 5 mmHg (5.3 ± 0.7 kPa) (group 40) or 60 ± 5 mmHg (8.0 ± 0.7 kPa) (group 60). Arterial blood gas analysis was performed at the start of the anaesthetic period (T0), at one point during the anaesthetic (T1), immediately prior to disconnection from the breathing system (T2) and at the first spontaneous breath in the recovery box (T3). The time from disconnection from the breathing system to return to spontaneous ventilation (RSV) was recorded. Data were analysed using a two sample t-test or the Mann-Whitney U-test and significance assigned when p < 0.05.

Results: Horses in group 60 resumed spontaneous breathing significantly earlier than those in group 40, [52 (14-151) and 210 (103-542) seconds, respectively] (p < 0.001). Arterial oxygen tension (PaO2 ), pH, base excess (BE) and plasma bicarbonate (HCO3-) were not different between the groups at RSV, however, PaO2 was significantly lower in group 60 during (T1) and at the end of anaesthesia (T2).

Conclusions And Clinical Relevance: Aiming to maintain intra-operative Pe'CO2 at 60 ± 5 mmHg (8.0 ± 0.7 kPa) in mechanically ventilated horses resulted in more rapid RSV compared with when Pe'CO2 was maintained at 40 ± 5 mmHg (5.3 ± 0.7 kPa).
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March 2016