Competency frameworks: which format for which target?

In veterinary medical education, it is now necessary to design competency frameworks (CFs) that list expected competencies at graduation. Three different CFs with different formats and contents have been published in Europe, such as the Day One Skills (DOS), the recommendations of the World Organization for Animal Health(OIE), and the Veterinary Professional (VetPro). In the current study, on the basis of a survey among Belgian veterinarians, a fourth document was designed that lists the necessary knowledge, skills, and attitudes grouped into families according to professional situations. The objectives of this study were to assess the perception of CFs by various categories of stakeholders, identify the possible uses of CFs, and determine whether one format should be preferred to another. We used a qualitative approach based on semi-structured face-to-face interviews with different stakeholders after they had reviewed the four different documents (CFs). This study showed that an obligation to design CFs was clearly perceived by academic and professional authorities. Teachers and veterinarians may be either enthusiastic or apprehensive about CFs, while students perceive the usefulness of the documents to plan and assess their learning objectives. Three main roles of CFs were identified: they can be used as communication tools, regulatory tools, or educational tools. However, not one of the documents used in this study was perceived to fulfill all roles. It is therefore likely that no one ideal document yet exists and a combination of formats is necessary.

Understanding veterinary practitioners' decision-making process: implications for veterinary medical education.

Understanding how veterinary practitioners make clinical decisions, and how they use scientific information to inform their decisions, is important to optimize animal care, client satisfaction, and veterinary education. We aimed to develop an understanding of private practitioners' process of decision making. On the basis of a grounded-theory qualitative approach, we conducted a telephone survey and semi-structured face-to-face interviews. We identified a decision-making framework consisting of two possible processes to make decisions, five steps in the management of a clinical case, and three influencing factors. To inform their decision, veterinary surgeons rarely take the evidence-based medicine (EBM) approach. They consult first-opinion colleagues, specialists, laboratories, and the Internet rather than scientific databases and peer-reviewed literature, mainly because of limited time. Most interviewees suggested the development of educational interventions to better develop decision-making skills in veterinary schools. Adequate information and EBM tools are needed to optimize the time spent in query and assessment of scientific information, and practitioners need to be trained in their use.

Acer pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species.

Acer pseudoplatanus is a worldwide-distributed tree which contains toxins, among them hypoglycin A (HGA). This toxin is known to be responsible for poisoning in various species, including humans, equids, Père David's deer and two-humped camels. We hypothesized that any herbivore pasturing with A. pseudoplatanus in their vicinity may be at risk for HGA poisoning. To test this hypothesis, we surveyed the HGA exposure from A. pseudoplatanus in species not yet described as being at risk. Animals in zoological parks were the major focus, as they are at high probability to be exposed to A. pseudoplatanus in enclosures. We also searched for a toxic metabolite of HGA (i.e., methylenecyclopropylacetyl-carnitine; MCPA-carnitine) in blood and an alteration of the acylcarnitines profile in HGA-positive animals to document the potential risk of declaring clinical signs. We describe for the first instance cases of HGA poisoning in Bovidae. Two gnus (Connochaetes taurinus taurinus) exposed to A. pseudoplatanus in their enclosure presented severe clinical signs, serum HGA and MCPA-carnitine and a marked modification of the acylcarnitines profile. In this study, even though all herbivores were exposed to A. pseudoplatanus, proximal fermenters species seemed less susceptible to HGA poisoning. Therefore, a ruminal transformation of HGA is hypothesized. Additionally, we suggest a gradual alteration of the fatty acid metabolism in case of HGA poisoning and thus the existence of subclinical cases.

Grazing Mares on Pasture with Sycamore Maples: A Potential Threat to Suckling Foals and Food Safety through Milk Contamination.

Equine atypical myopathy (AM) is seasonal intoxication resulting from the ingestion of seeds and seedlings of the sycamore maple (Acer pseudoplatanus) that contain toxins, among them, hypoglycin A (HGA). Literature mentions several cases of AM among gravid mares and in unweaned foals. The objective of this study was to determine whether HGA and/or its metabolite are present in milk from grazing mares exposed to sycamore maple trees as confirmed by detection of HGA and its metabolite in their blood. Four mare/foal couples were included in the study. Both HGA and its metabolite were detectable in all but one of the milk samples. To our knowledge, this is the first study describing transfer of HGA to the milk. This unprecedented observation could partially explain cases of unweaned foals suffering from AM. However, a transplacental transfer of the toxin cannot be excluded for newborn foals. Besides being a source of contamination for offspring, milk contamination by toxins from fruits of trees of the Sapindaceae family might constitute a potential risk for food safety regarding other species' raw milk or dairy products.

Answers to the Frequently Asked Questions Regarding Horse Feeding and Management Practices to Reduce the Risk of Atypical Myopathy.

In 2014, atypical myopathy (AM) was linked to Acer pseudoplatanus (sycamore maple) in Europe. The emergence of this seasonal intoxication caused by a native tree has raised many questions. This manuscript aims at answering the five most frequently asked questions (FAQs) regarding (1) identification of toxic trees; reduction of risk at the level of (2) pastures and (3) equids; (4) the risk associated with pastures with sycamores that have always been used without horses being poisoned and (5) the length of the risk periods. Answers were found in a literature review and data gathered by AM surveillance networks. A guide is offered to differentiate common maple trees (FAQ1). In order to reduce the risk of AM at pasture level: Avoid humid pastures; permanent pasturing; spreading of manure for pasture with sycamores in the vicinity and avoid sycamore maple trees around pasture (FAQ2). To reduce the risk of AM at horse level: Reduce pasturing time according to weather conditions and to less than six hours a day during risk periods for horses on risk pasture; provide supplementary feeds including toxin-free forage; water from the distribution network; vitamins and a salt block (FAQ3). All pastures with a sycamore tree in the vicinity are at risk (FAQ4). Ninety-four percent of cases occur over two 3-month periods, starting in October and in March, for cases resulting from seeds and seedlings ingestion, respectively (FAQ5).

Postanaesthetic effects of ketamine-midazolam and ketamine-medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane.

BACKGROUND: Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine-midazolam (KMZ) versus ketamine-medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits anaesthetised with isoflurane. METHODS: This was a cross-over, randomised, single-blinded, controlled, experimental trial. Seven healthy adult New Zealand White rabbits were used. Gastrointestinal transit time was assessed by contrast radiography in awake rabbits. Presence of contrast medium in the small intestine (gastric transit time), in the caecum (small intestinal transit time) and in faeces in the colon was assessed. One week later, 55 minutes isoflurane anaesthesia was induced with ketamine (15 mg/kg) and either midazolam (3 mg/kg) or medetomidine (0.25 mg/kg) by intramuscular injection. Thirty minutes after discontinuation of isoflurane, atipamezole (0.5 mg/kg) was administered only to rabbits in KMT-A treatment. Gastrointestinal transit time was then assessed in both treatment groups, beginning 30 minutes after cessation of isoflurane administration. Two weeks later, the treatment groups were interchanged. RESULTS: Gastric and small intestinal transit times were significantly longer with KMT-A (92±109 minutes and 214±119 minutes, respectively) than with KMZ (1±0 minutes and 103±6 minutes, respectively) and in the awake state (7±7 minutes and 94±32 minutes, respectively). CONCLUSION: Clinicians should therefore be aware of the potential gastrointestinal side effects of KMT-A, particularly in rabbits at risk for gastrointestinal stasis.

A pilot study comparing the antispasmodic effects of inhaled salmeterol, salbutamol and ipratropium bromide using different aerosol devices on muscarinic bronchoconstriction in healthy cats.

This study compared the duration and magnitude of the antispasmodic effects of salmeterol (SLM), salbutamol (SAL), ipratropium bromide (IB) and the combination of SAL and IB (SAL/IB) against carbachol-induced bronchoconstriction in healthy cats, and investigated the gain in efficacy using a two or fourfold increase in drug dosages. The drug regimens used were: (1) SLM 25 microg, SAL 100 microg, IB 20 microg and SAL/IB 100 microg/20 microg for bronchodilators delivered by a metered-dose inhaler (MDI); (2) SAL 3.75 mg and IB 62.5 microg for nebulised (NEB) medications. To monitor the bronchodilator effect, airway responsiveness was assessed at different time points using barometric whole-body plethysmography and calculation of the concentration of inhaled carbachol inducing a 300% increase of baseline Penh (enhanced pause), an estimator of airflow limitation. Maximum C-Penh300 was recorded 15 min after NEB SAL, IB MDI, NEB IB and 1h after SAL MDI and 4h after SLM MDI, respectively. C-Penh300 was significantly different from control values (without treatment) up to 24h for SLM MDI, 8h for IB MDI and 4h for other drugs. In terms of efficacy, SAL/IB MDI showed a synergistic antispasmodic effect at 15 min, 4h and 8h after administration. A fourfold increase of the initial dose of IB MDI and NEB IB significantly increased C-Penh300. Despite a fourfold dose increase, SLM displayed the weakest degree of bronchoprotection compared to other bronchodilators. The study provides evidence that inhaled bronchodilators are efficient at preventing muscarinic-induced bronchospasm in healthy cats and that SAL and IB appear to be short-acting bronchodilators in contrast to SLM.

Potential new sources of hypoglycin A poisoning for equids kept at pasture in spring: a field pilot study.

Equine atypical myopathy in Europe results from hypoglycin A (HGA) exposure through the ingestion of samaras or seedlings of the sycamore maple tree. This pilot study aimed at better defining sources of HGA intoxication in spring. Samaras fallen on the ground and then seedlings were collected at two-week intervals from sycamore, Norway, and field maple trees over the spring 2016. In early April, rainwater from wet seedlings collected after a rainy night was harvested to be analysed. Mid-May, samaras of the box elder, common ash, and inflorescences of sycamore maples were collected on the tree. Quantification of HGA in samples was performed using high performance thin layer chromatography. Hypoglycin A was detected in all samples from sycamore including rainwater but tested negative for Norway, field maples. The samaras of the box elder found in the present study area did not contain a seed within their husk and thus tested negative. From the maximum HGA concentrations found, it may be extrapolated that at some periods and locations, about 20 g of samaras, 50 seedlings, 150 g of inforescences or 2 liters of water that has been in contact with seedlings would contain the maximum tolerated dose per day for a horse.

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats.

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70µg/15ml or 350µg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70µg/15ml) or budesonide (250µg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

Non-invasive assessment of airway responsiveness in healthy and allergen-sensitised cats by use of barometric whole body plethysmography.

This study aimed at determining whether airway responsiveness (AR) tests performed by use of barometric whole body plethysmography (BWBP) were repeatable in cats and to what extent AR was affected by the nebulization protocol used, the age of the animals, the inflammatory status of the airways and prior bronchodilator treatment. Repeatability of AR was tested on two occasions in 30 healthy cats. The concentration of carbachol inducing a 300% increase of the enhanced pause (Penh)--an estimator of airflow limitation--was calculated (C-Penh300) and did not differ significantly between the two tests (0.035+/-0.017% compared to 0.034+/-0.016%) and was significantly and positively correlated. The comparison between rapidly and slowly increasing carbachol concentrations was performed in ten healthy cats and showed a significantly lower C-Penh300 (%) when slowly increasing concentrations were used (0.037+/-0.013% compared to 0.039+/-0.015%, P<0.05). A significant age-related increase of C-Penh300 was evidenced by performing AR tests in 15 healthy cats at 12, 18, 24 and 30 months (12 months: 0.026+/-0.008%, 18 months: 0.031+/-0.009%, 24 months: 0.038+/-0.01%, 30 months: 0.043+/-0.014%, P<0.05). C-Penh300 significantly decreased in 12 Ascaris suum-sensitised cats after allergen exposure (0.026+/-0.016% compared to 0.033+/-0.016%, P<0.05) and was negatively correlated with the granulocyte percentage of bronchoalveolar lavage fluid (r=-0.36, P<0.01). Compared with a placebo inhalation, pre-treatment with inhaled salbutamol significantly increased C-Penh300 in four healthy cats (0.093+/-0.021% compared to 0.036+/-0.004%, P<0.05). This study provides evidence that AR determination by use of BWBP is promising as non-invasive indicator of lower airway inflammation or for monitoring response to bronchodilator treatment.

Functional, inflammatory and morphological characterisation of a cat model of allergic airway inflammation.

The aims of this study were to characterise a model of feline allergic airway inflammation and to test through a longitudinal investigation whether five repeated allergen exposures would lead to signs of airway remodelling that would be detectable in vivo. Eight healthy control cats and eight cats sensitised with Ascaris suum allergens were investigated. Barometric whole body plethysmography (BWBP) was used for the assessment of respiratory variables and airway responsiveness (AR). Bronchoalveolar lavage fluid (BALF) was sampled for cytology and determination of F(2)-isoprostane concentration and matrix metalloproteinase type 9 (MMP-9) activity. Thoracic radiography and bronchoscopy scores were also established. Cats were investigated prior to sensitisation and after inhalation of placebo or allergen challenge 1. BWBP measurements revealed a significant increase of enhanced pause (Penh), an index of bronchoconstriction, and AR in sensitised cats in response to allergen challenge 1. A significant increase in BALF neutrophil and eosinophil %, F(2)-isoprostane concentration and MMP-9 activity, and increased radiography and bronchoscopy scores were recorded. After a recovery period of 6 weeks, all variables except BALF MMP-9 returned to baseline values. Four further allergen challenges induced similar changes to those seen in challenge 1 and no signs of persistent changes suggestive of bronchial remodelling were detectable. The model provides an in vivo approach to functional, inflammatory and morphological changes occurring in response to single and repeated allergen exposure.

Effects of age and allergen-induced airway inflammation in cats: radiographic and cytologic correlation.

Thoracic radiography is an important diagnostic tool for feline respiratory medicine. The aim of this study was (1) to assess age-related changes of thoracic radiographic views in healthy young cats and (2) to test if experimentally-induced bronchial inflammation by inhaling Ascaris suum (AS) allergens leads to radiographic changes after single or repeated exposures. Healthy cats (n=15-30) aged between 6 and 30 months were evaluated. Eight healthy cats and eight AS-sensitised cats, respectively, inhaled sterile saline or allergen. Radiographs were taken 24h before, and 6, 24 and 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed after the last radiographic examination. AS-sensitised cats underwent three further allergen challenges at 3-month intervals. The radiographic evaluation was based on a scoring system considering bronchial, interstitial and alveolar patterns. A significant age-related increase in interstitial and total radiographic score was detected in healthy cats older than 18 months and in healthy cats older than 24 months. Whilst saline inhalation did not affect radiographic scores, a single AS challenge induced significant changes of all scores within 6-24h. A significant positive correlation between radiographic scores and BAL neutrophils and eosinophils was found. Repeated AS challenges did not induce irreversible changes in radiographic scores.

Airway inflammation in cadmium-exposed rats is associated with pulmonary oxidative stress and emphysema.

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Evaluation of respiratory function by barometric whole-body plethysmography in healthy dogs.

The objective of the present study was to assess the validity of barometric whole-body plethysmography (BWBP), to establish reference values, and to standardise a bronchoprovocative test to investigate airway responsiveness using BWBP in healthy dogs. BWBP measurements were obtained from six healthy beagle dogs using different protocols: (1) during three consecutive periods (3.5min each) in two morning and two evening sessions; (2) before and after administration of two protocols of sedation; (3) before and after nebulisation of saline and increasing concentrations of carbachol and histamine both in conscious dogs and in dogs under both protocols of sedation. Enhanced pause (PENH) was used as index of bronchoconstriction. Basal BWBP measurements were also obtained in 22 healthy dogs of different breeds, age and weight. No significant influence of either time spent in the chamber or daytime was found for most respiratory variables but a significant dog effect was detected for most variables. A significant body weight effect was found on tidal volume and peak flow values (P<0.05). Response to carbachol was not reproducible and always associated with side effects. Nebulisation of histamine induced a significant increase in respiratory rate, peak expiratory flow, peak expiratory flow/peak inspiratory flow ratio and PENH (P<0.05). The response was reproduced in each dog at different concentrations of histamine. Sedation with acepromazine+buprenorphine had little influence on basal measurements and did not change the results of histamine challenge. It was concluded that BWBP is a safe, non invasive and reliable technique of investigation of lung function in dogs which provides new opportunities to characterise respiratory status, to evaluate airway hyperresponsiveness and to assess therapeutic interventions.

Non-invasive assessment of growth, gender and time of day related changes of respiratory pattern in healthy cats by use of barometric whole body plethysmography.

The objective of this study was to establish a reference base for respiratory variables (respiratory rate [R(R)], inspiratory and expiratory time [T(i) and T(e)], peak inspiratory and expiratory pseudoflow [PIF and PEF], tidal volume [V(T)], minute ventilation [V(E)] and enhanced pause [Penh]) of healthy cats by use of barometric whole body plethysmography (BWBP). Eighteen healthy European cats (10 male, 8 female) were studied from the age of 3 to 13 months in order to assess growth- and gender-related changes of BWBP variables. Chest radiographs and bronchoalveolar lavage cytology were performed to confirm pulmonary health status. Diurnal changes were investigated every 2 h over a period of 24 h when the cats were adult. V(T), V(E), PIF and PEF significantly increased during somatic growth and were higher in males than in females, whereas R(R), T(i), T(e), T(e)/T(i) ratio, PEF/PIF ratio and Penh remained unchanged and were not affected by gender. When measured over 24 h, Penh, T(e) and T(i) were significantly increased in the early morning hours (04:00 h), whereas R(R), PIF and PEF were decreased at that time. This study provides reference values of BWBP variables for healthy male and female cats and indicates when circadian changes might be observed.

Inhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis.

This study investigated the effect of inhaled fluticasone on lower airway inflammation and bronchial responsiveness (BR) to inhaled carbachol in cats with very mild, chronic bronchitis (n = 5) that were compared with healthy cats serving as controls (n = 6). Chest radiographs, BR tests performed non-invasively by barometric whole body plethysmography (BWBP) and bronchoalveolar lavage (BAL) were performed before and after treatment. BR was quantified by calculating the concentration of carbachol inducing bronchoconstriction (C-Penh300%), defined as a 300% increase of baseline Penh, an index of bronchoconstriction obtained by BWBP. BAL fluid was analyzed cytologically and the oxidant marker 8-iso-PGF2alpha was determined. At test 1, healthy cats and cats with bronchitis were untreated, whereas for test 2 inhalant fluticasone (250 microg once daily) was administrated for 2 consecutive weeks to cats with bronchitis. Control cats remained untreated. Inhaled fluticasone induced a significant increase in C-Penh300% and a significant decrease of BAL fluid total cells, macrophages, neutrophils and 8-iso-PGF2alpha in cats with bronchitis, whilst untreated control cats did not show significant changes over time. This study shows that a 2-week fluticasone treatment significantly reduced lower airway inflammation in very mild bronchitis. BR could be successfully monitored in cats using BWPB and decreased significantly in response to inhaled fluticasone. 8-Iso-PGF2alpha in BAL fluid was responsive to treatment and appeared as a sensitive biomarker of lower airway inflammation in cats.

Assessment of a computed tomography guided injection technique of the lumbo-sacral disc in sheep.

OBJECTIVES: Recent data indicate that degeneration of intervertebral discs occurs naturally in sheep, with a higher prevalence at the level of the lumbo-sacral disc. The objective of this ex vivo study was to evaluate a computed tomography (CT) guided method of injection into the ovine lumbo-sacral disc. METHODS: Six euthanatized sheep were used for identification of the approach plane, the optimal direction of the needle and the mean distance from skin to disc. Dissection after injection of coloured ink was used to determine the anatomical structures that were penetrated. In seven other animals, all spines were assessed beforehand by CT and magnetic resonance imaging to determine whether disc pathology was present. The final position of the needle was assessed by CT to determine the accuracy of the technique. Contrast agent was injected to identify any problems associated with administration of liquid into the disc. RESULTS: The CT guided injection technique was easy to perform and enabled adequate positioning of the needle into all (n = 7) lumbo-sacral discs. Distance between the skin and the disc ranged between 12 and 17 cm. No organ, vascular or nervous structure was penetrated and the needle path remained intramuscular without penetration of the peritoneal cavity. Contrast medium leaked out through three degenerate discs. CLINICAL SIGNIFICANCE: The current study described a consistently safe and accurate CT guided injection technique to the lumbo-sacral disc for future in vivo experimental studies that will use sheep as animal model for human intervertebral disc disease disease.

Residues in Beeswax: A Health Risk for the Consumer of Honey and Beeswax?

A scenario analysis in regard to the risk of chronic exposure of consumers to residues through the consumption of contaminated honey and beeswax was conducted. Twenty-two plant protection products and veterinary substances of which residues have already been detected in beeswax in Europe were selected. The potential chronic exposure was assessed by applying a worst-case scenario based on the addition of a "maximum" daily intake through the consumption of honey and beeswax to the theoretical maximum daily intake through other foodstuffs. For each residue, the total exposure was finally compared to the acceptable daily intake. It is concluded that the food consumption of honey and beeswax contaminated with these residues considered separately does not compromise the consumer's health, provided proposed action limits are met. In regard to residues of flumethrin in honey and in beeswax, "zero tolerance" should be applied.

Comparison between pulmonary resistance and Penh in anaesthetised rats with tracheal diameter reduction and after carbachol inhalation.

INTRODUCTION: Single-chambered barometric whole-body plethysmography is frequently used as a noninvasive lung function test. However, the validity of the enhanced Pause (Penh), an index of airflow limitation, remains controversial. We compared Penh with pulmonary resistance (R(L)) to test whether Penh detects tracheal subobstruction and carbachol-induced airflow limitation in spontaneously breathing, anaesthetised rats. METHODS: Fourteen male Sprague-Dawley rats underwent tracheal catheterisation, followed by measurements of R(L) and Penh. Six rats underwent tracheal subobstruction by the consecutive insertion into the lumen of the tracheal tube of two catheters of decreasing diameter. Eight rats received an inhaled saline challenge, followed by two noncumulative nebulizations of carbachol (1.25 mg/mL, 1 min). RESULTS: In rats with tracheal calibre reductions, R(L) significantly increased at each reduction (0.218+/-0.052 vs. 0.417+/-0.058 vs. 0.820+/-0.258 cm H(2)O/mL s, p<0.05), whereas Penh only increased after the last reduction (1.88+/-0.25 vs. 2.47+/-0.26, p<0.05). Increases (Delta) of R(L) and Penh were not correlated. In comparison to postsaline values, carbachol induced a significant increase of Penh (1.93+/-0.44 vs. 4.05+/-1.45, p<0.005) and R(L) (0.137+/-0.04 vs. 0.284+/-0.084 cm H(2)O/mL.s, p<0.005). DeltaPenh and DeltaR(L) were significantly correlated (r=0.80, p<0.05). DISCUSSION: This study showed, by comparing Penh with R(L), that single-chambered plethysmography measuring Penh allows to detect carbachol-induced airflow limitation in spontaneously breathing, anaesthetised Sprague-Dawley rats, but poorly detects an increase in R(L) due to tracheal calibre reductions. These findings suggest that Penh might be only be used as an index of airflow limitation under well-defined experimental conditions.

Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model.

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. It has been suggested that ultrafine particles are able to translocate from the airways into the bloodstream in vivo. We have investigated this in an isolated perfused and ventilated rabbit lung preparation lacking pulmonary lymphatic flow. Fluorescent polystyrene particles of different diameters (24, 110 or 190 nm) and surface chemistry (carboxylate or amine modified) were injected either intratracheally (i.t.) or intravascularly (i.v.) and, after a period of 2 h, their presence in the perfusion liquid or in the bronchoalveolar lavage (BAL) fluid, was assessed by spectrofluorimetry. Vascular pressures and lung weights were monitored. Following the i.t. administration, no particle translocation was observed from the alveoli into the vascular compartment. Similarly, no particle translocation was found after i.v. administration of particles. However, when microvascular permeability was pharmacologically increased by administering histamine (10(-4) M) in the vascular compartment, inducing a positive driving force provided by fluid filtration, a fluorescent signal in BAL was recorded (2.5 +/- 1% of the dose of particles administered), suggesting a translocation of particles through the alveolo-capillary barrier. We conclude that ultrafine polystyrene particles cannot significantly diffuse from lung into the vascular compartment in our model, but they are able to translocate in the opposite direction when the microvascular permeability is increased by histamine. The relevance of these ex vivo findings for the in vivo translocation of inhaled ultrafine particles remains to be established.