Respiratory Responses to Single Oral Administration of Taurine in Sprague-Dawley Rats.

Taurine is a nonessential amino acid that has been increasingly consumed due to its various beneficial biological effects. Excessive taurine intake has been linked to the positive regulation of inflammatory responses and endoplasmic reticulum stress through the modulation of intracellular calcium levels. However, research on the potential adverse effects of taurine consumption on the respiratory system is limited. To address this, we investigated the respiratory responses of 6-week-old male Sprague-Dawley rats to taurine administered orally at 0, 100, 200, and 400 mg/kg. Respiratory rate, tidal volume, and minute volume were monitored in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. We found that taurine administration did not significantly alter respiratory rate or tidal volume; however, a significant increase in minute volume was observed 6 h after administration of 200 mg/kg taurine.

Assessing breathing effort by barometric whole-body plethysmography and its relationship with prognosis in client-owned cats with respiratory distress.

BACKGROUND: Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. HYPOTHESIS: Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. ANIMALS: Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. METHODS: This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected. RESULTS: Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.

Respiratory Safety Pharmacological Testing with Single Intravenous Administration of Caffeine in Sprague-Dawley Rats.

As caffeine consumption continues to increase, both positive and negative effects are becoming evident. Caffeine directly affects the cardiovascular system, including heart function and rate. Thus, understanding the current respiratory safety pharmacological responses is of utmost importance. To elucidate the respiratory safety pharmacological characteristics of caffeine, male Sprague-Dawley rats, aged 6 weeks, were intravenously administered doses of 0, 2, 6, and 20 mg/kg of caffeine. Respiratory rate, tidal volume, and minute volume were subsequently measured. In this study, we observed a significant increase in respiratory rate and minute volume, but a remarkable reduction in tidal volume following the intravenous administration of caffeine at doses exceeding 6 mg/kg. These changes were evident within the timeframe of 0.25 to 1.5 h. The data we have collected can serve as valuable foundational scientific information for future research on caffeine, encompassing absorption, distribution, metabolism, excretion, and pharmacological core-battery experiments.

Exposición a sílice de mineros en altitud. Dosis inhalada, método de evaluación en condición de hipobariaV / Silica exposure among miners at high altitude. Inhaled dose and evaluation methods in hypobaric environments

Objetivo: Evaluar la exposición a sílice de mineros chilenos en altitud usando diferentes metodologías, con el propósito de determinar el método más seguro para controlar la ex-posición. Métodos: Los 46 mineros que conforman la muestra trabajan a 3000 metros sobre el nivel del mar con sistema de turnos no convencionales, en jornadas de 12 horas diarias por 4 días consecutivos, después de los cuales se descansa por otros 4 días. Se tomaron mues-tras de sílice en cada uno de los puestos de trabajo de estos 46 mineros en altitud. Los re-sultados de las concentraciones se presentan en (mg/m3). La exposición se evaluó usando el Threshold Limit Value y otras dos metodologías que incorporan parámetros respiratorios. Se determinó el grupo de mineros en riesgo con cada uno de estos métodos y se comparó la proporción de mineros expuestos en cada caso.Resultados: evaluando con el Threshold Limit Value (método 1) se obtuvo un 43,48% de mi-neros en riesgo. Con los métodos que incluyen parámetros respiratorios se obtuvo una pro-porción de mineros sobre-expuestos del 82,61% con el método 2, y 73,91% con el método 3.Conclusiones: de los tres métodos analizados, el que considera el parámetro respiratorio volumen minuto, a través de la estimación de la dosis inhalada, es el más seguro para defi-nir el grupo de mineros en riesgo por exposición a sílice a gran altura (AU)

Objective: To evaluate silica exposure among Chilean miners at high altitude, using dif-ferent methodological approaches, for the purpose of determining the safest method to control exposures. Methods: The 46 miners in the sample worked at 3000 meters above sea level in nonstan-dard work shifts, consisting of four consecutive 12-hour days, followed by four consecutive days off. Silica samples were obtained in each of the jobs positions of these 46 high-altitude miners. The results of the concentrations are presented in mg/m3. Exposures were evalu-ated in compatison to the Threshold Limit Value (Method 1) and using two other methodol-ogies that incorporate respiratory parameters (Methods 2 and 3). The proportion of miners at risk was determined with each of these methods and compared.Results: Based on the Threshold Limit Value (Method 1), 43.48% of miners were classified as being at risk. With the other two methods that incorporate respiratory parameters, the proportion of overexposed miners was 82.61% with Method 2, and 73.91% with Method 3.Conclusions: Of the three methods analyzed, the one that considers the respiratory param-eter minute volume, through the estimation of the inhaled dose, is the safest to define the group of miners at risk due to exposure to silica at high altitude (AU)

Theophylline reverses oxycodone's but not fentanyl's respiratory depression in mice while caffeine is ineffective against both opioids.

RATIONALE: The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent years the increasing incidence of opioid-involved overdose deaths has been driven by fentanyl, which is more resistant to adequate reversal by naloxone (NARCAN ®) than semi-synthetic or classical morphinan predecessors like oxycodone and heroin. For this and other reasons (e.g., precipitating withdrawal) non-opioidergic pharmacotherapies to reverse opioid-depressed respiration are needed. Methylxanthines are a class of stimulant drugs including caffeine and theophylline which exert their effects primarily via adenosine receptor antagonism. Evidence suggests methylxanthines can stimulate respiration by enhancing neural activity in respiratory nuclei in the pons and medulla independent of opioid receptors. This study aimed to determine whether caffeine and theophylline can stimulate respiration in mice when depressed by fentanyl and oxycodone. METHODS: Whole-body plethysmography was used to characterize fentanyl and oxycodone's effects on respiration and their reversal by naloxone in male Swiss Webster mice. Next, caffeine and theophylline were tested for their effects on basal respiration. Finally, each methylxanthine was evaluated for its ability to reverse similar levels of respiratory depression induced by fentanyl or oxycodone. RESULTS AND CONCLUSIONS: Oxycodone and fentanyl dose-dependently reduced respiratory minute volume (ml/min; MVb) that was reversible by naloxone. Caffeine and theophylline each significantly increased basal MVb. Theophylline, but not caffeine, completely reversed oxycodone-depressed respiration. In contrast, neither methylxanthine elevated fentanyl-depressed respiration at the doses tested. Despite their limited efficacy for reversing opioid-depressed respiration when administered alone, the methylxanthines safety, duration, and mechanism of action supports further evaluation in combination with naloxone to augment its reversal of opioid-depressed respiration.

Parameters of high-frequency jet ventilation using a mechanical lung model.

High frequency jet ventilationis a mechanical lung ventilation method which uses a relatively high flow usually through an open system. This work examined the effect of high-frequency jet ventilation on respiratory parameters of an intubated patient simulated using a high-frequency jet ventilator attached to a ventilation monitor for measurements of ventilation parameters. The series of experiments altered specific parameters each time (respiratory rate, inspiratory-expiratory (I:E) ratio, and inspiratory pressure), under different lung compliances. A reduction of minute ventilation was observed alongside a rise in respiratory rate, with low airway pressures over the entire range of lung compliances. In addition, an I:E ratio of 2:1 to 1:1; and the tidal and minute volumes were directly related to the inspiratory pressure over all compliance settings. To conclude, the respiratory mechanics in high-frequency jet ventilation are very different from those of conventional rate ventilation in a lung model. Further studies on patients and/or a biological model are needed to investigate pCO2 and end-tidal carbon-dioxide during high-frequency jet ventilation.

The use of hypercapnic conditions to assess opioid-induced respiratory depression in rats.

INTRODUCTION: Whole-body plethysmography (WBP) in unrestrained, non-anesthetized rodents is a preclinical method to assess the respiratory depressant effects of opioids, the leading cause of opioid overdose death in humans. However, low baseline respiration rates under normocapnic conditions (i.e., "floor" effect) can render the measurement of respiratory decreases challenging. We assessed hypercapnia-induced increases in respiration as a strategy to assess opioid-induced decreases in respiration in rats. METHODS: WBP was used to assess respiration frequency, tidal volume and minute volume in the presence of normocapnic and hypercapnic (8% CO2) conditions in rats during the rat diurnal period of the light cycle. The mu-opioid receptor agonist fentanyl was administered intravenously, and the hot plate test was used to assess acute antinociception. RESULTS AND DISCUSSION: Hypercapnia-induced increases in respiratory parameters (frequency, minute volume, and tidal volume) were decreased by fentanyl at doses that did not decrease the same parameters under the normocapnic conditions. These findings show that hypercapnia increases sensitivity to respiratory depressant effects of fentanyl, as compared with assessments during the rat diurnal period when activity and breathing rate are generally low, i.e., there is a floor effect. The current approach is highly sensitive to opioid-induced respiratory depression, and therefore provides a useful method for assessment in a pre-clinical setting.

Patterns of adaptive servo-ventilation settings in a real-life multicenter study: pay attention to volume! : Adaptive servo-ventilation settings in real-life conditions.

BACKGROUNDS: To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). METHODS: The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer's software for 6 months. RESULTS: One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25-75) initial Apnea-Hypopnea-Index of 50 (38-62)/h, an ASV-treatment duration of 2.88 (1.76-4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p < 0.001). MV differences between ASV-F (p = 0.002) and ASV-V (p < 0.001) were not homogenously distributed across clusters, suggesting specific cluster and ASV-algorithm interactions. Individual ASV-data suggest that the hyperventilation risk is not related to the cluster nor the ASV-monitoring type. CONCLUSIONS: Real-life ASV settings are associated with combinations of baseline and follow-up variables wherein cardiological variables remain clinically meaningful. At the patient level, a hyperventilation risk exists regardless of cluster or ASV-monitoring type, spotlighting a future role of MV-telemonitoring in the interest of patient-safety. TRIAL REGISTRATION: The OTRLASV study was registered on ClinicalTrials.gov (Identifier: NCT02429986 ). 1 April 2015.

A pilot study of minimum operational flow for loose-fitting powered air-purifying respirators used in healthcare cleaning services.

The objective of this pilot study was to determine the minimum operational flow for loose-fitting powered air-purifying respirators (PAPR) used in healthcare cleaning services. An innovative respiratory flow recording device was worn by nine healthcare workers to obtain the minute volume (MV, L/min), mean inhalation flow (MIF, L/min), and peak inhalation flow (PIF, L/min) while performing "isolation unit work" (cleaning and disinfecting) of a patient room within 30 min. The MV and PIF were compared with the theoretical values obtained from an empirical formula. The correlations of MV, MIF, and PIF with subjects' age, weight, height, body surface area (ADu), and body mass index (BMI) were analyzed. The average MV, MIF, and PIF were 33, 74, and 107 L/min, with maximal airflow rates of 41, 97, and 145 L/min, respectively, which are all below the current 170 L/min minimum operational flow for NIOSH certified loose-fitting PAPRs.

Mid-cervical spinal cord contusion causes robust deficits in respiratory parameters and pattern variability.

Mid-cervical spinal cord contusion disrupts both the pathways and motoneurons vital to the activity of inspiratory muscles. The present study was designed to determine if a rat contusion model could result in a measurable deficit to both ventilatory and respiratory motor function under "normal" breathing conditions at acute to chronic stages post trauma. Through whole body plethysmography and electromyography we assessed respiratory output from three days to twelve weeks after a cervical level 3 (C3) contusion. Contused animals showed significant deficits in both tidal and minute volumes which were sustained from acute to chronic time points. We also examined the degree to which the contusion injury impacted ventilatory pattern variability through assessment of Mutual Information and Sample Entropy. Mid-cervical contusion significantly and robustly decreased the variability of ventilatory patterns. The enduring deficit to the respiratory motor system caused by contusion was further confirmed through electromyography recordings in multiple respiratory muscles. When isolated via a lesion, these contused pathways were insufficient to maintain respiratory activity at all time points post injury. Collectively these data illustrate that, counter to the prevailing literature, a profound and lasting ventilatory and respiratory motor deficit may be modelled and measured through multiple physiological assessments at all time points after cervical contusion injury.

Assessment of Two Personal Breathing Recording Devices in a Simulated Healthcare Environment.

BACKGROUND: In the field of respiratory protection for healthcare workers (HCWs), few data are available on respiratory airflow rate when HCWs are performing their work activities. The objective of this study was to assess the performance of two wearable breathing recording devices in a simulated healthcare environment. METHODS: Breathing recording devices from two different manufactures "A" and "B" were assessed using 15 subjects while performing a series of simulated healthcare work activities (patient assessment; vitals; IV treatment; changing linen; carrying weight while walking; normal breathing while standing). The minute volume (MV, L/min), mean inhalation flow (MIF, L/min), peak inhalation flow (PIF, L/min), breathing frequency (f, breaths/min), and tidal volume (TV, L/min) measured by each device were analyzed. Bland-Altman method was applied to explore the variability of devices A and B. Duncan's multiple range test was used to investigate the differences among activity-specific inspiratory flow rates. RESULTS: The average MV, MIF and PIF reported by device A were 23, 54, and 82 L/min with 95% upper confidence intervals (CIs) of 25, 60 and 92 L/min; the mean differences of MV, MIF and PIF presented by the two units of device A were 0.9, 1.3, and 2.8 L/min, respectively. The average values and mean differences of MV, MIF and PIF found with device B were significantly higher than device A (P<0.05), showing a high variability. During non-speech activities, the PIF/MV and MIF/MV ratios were >3.14 and >2, while with speech, the ratios increased to >6 and >3. The f during speech (15 breaths/min) was significantly lower than non-speech activities (20-25 breaths/min). Among different simulated work activities, the PIF of "patient assessment" was the highest. CONCLUSIONS: This study demonstrated a novel approach to characterize respiratory flow for healthcare workers using an innovative wearable flow recording device. Data from this investigation could be useful in the development of future respirator test standards.

Correlation between transition percentage of minute volume (TMV%) and outcome of patients with acute respiratory failure.

PURPOSE: We have previously shown in patients receiving adaptive support ventilation (ASV) that there existed a Transition %MinVol (TMV%) where the patient's work of breathing began to reduce. In this study, we tested the hypothesis that higher TMV% would be associated with poorer outcome in patients with acute respiratory failure. MATERIALS AND METHODS: In this prospective observational study, we recruited patients with acute respiratory failure on ASV between December 2012 and September 2013 in a mixed ICU. The TMV% was determined by adjusting % MinVol until mandatory respiratory frequency was between 0 and 1breath/min. TMV% was measured on the first two days of mechanical ventilation. RESULTS: A total of 337 patients (age: 70±16years) were recruited. In patients whose TMV% increased between Day 1 and Day 2, aOR for mortality was 7.0 (95%CI=2.7-18.3, p<0.001) compared to patients whose TMV% decreased. In patients whose TMV% was unchanged between Day 1 and Day2, aOR for mortality was 3.91 (95%CI=1.80-8.22, p<0.01). CONCLUSIONS: An increase, or lack of decrease, of TMV% from Day 1 to Day 2 was associated with higher risk of in-hospital death.

Excretion characteristics of tetrabromobisphenol-A in Wistar rats following mouth and nose inhalation exposure.

Tetrabromobisphenol-A (TBBPA), a brominated flame retardant with the largest production volume worldwide, is employed as a reactive and additive flame retardant, and also as an intermediate in the production of other retardants. The constant release of TBBPA into the environment has attracted increasing attention to its potent health effects. To date, the vast majority of health-related research on TBBPA has focused on oral exposure. This study aims to explore the excretion characteristics of TBBPA in living organisms following inhalation exposure. An inhalation exposure system was established in which the experimental animal model was exposed to inhalable particles (diameter < 10 µm) of TBBPA. The TBBPA aerosol doses used were 12.9, 54.6, 121.6, and 455.0 mg/m3 according to tuning system parameters. Following 14 d (2 h/d) of repeated inhalational exposure, the primary route of elimination was in feces for all exposed groups, and the values showed a significant positive linear relationship with exposure dose. In contrast, the elimination amount in urine was less than 0.4% of the inhaled dose. Trace levels of TBBPA (less than 0.1% of the inhaled dose) were also detected in serum, with amounts varying from 0 to 844 ng (per rat) among all groups.

A linear model for event-related respiration responses.

BACKGROUND: Cognitive processes influence respiratory physiology. This may allow inferring cognitive states from measured respiration. Here, we take a first step towards this goal and investigate whether event-related respiratory responses can be identified, and whether they are accessible to a model-based approach. NEW METHOD: We regard respiratory responses as the output of a linear time invariant system that receives brief inputs after psychological events. We derive average responses to visual targets, aversive stimulation, and viewing of arousing pictures, in interpolated respiration period (RP), respiration amplitude (RA), and respiratory flow rate (RFR). We then base a Psychophysiological Model (PsPM) on these averaged event-related responses. The PsPM is inverted to yield estimates of cognitive input into the respiratory system. This method is validated in an independent data set. RESULTS: All three measures show event-related responses, which are captured as non-zero response amplitudes in the PsPM. Amplitude estimates for RA and RFR distinguish between picture viewing and the other tasks. This pattern is replicated in the validation experiment. COMPARISON WITH EXISTING METHODS: Existing respiratory measures are based on relatively short time-intervals after an event while the new method is based on the entire duration of respiratory responses. CONCLUSION: Our findings suggest that interpolated respiratory measures show replicable event-related response patterns. PsPM inversion is a suitable approach to analysing these patterns, with a potential to infer cognitive processes from respiration.

Antenatal substance misuse and smoking and newborn hypoxic challenge response.

OBJECTIVES: Infants of smoking (S) and substance misusing (SM) mothers have an increased risk of sudden infant death syndrome. The aim of this study was to test the hypothesis that infants of SM or S mothers compared with infants of non-SM, non-smoking mothers (controls) would have a poorer ventilatory response to hypoxia, which was particularly marked in the SM infants. DESIGN: Physiological study. SETTING: Tertiary perinatal centre. PATIENTS: 21 SM; 21 S and 19 control infants. Infants were assessed before maternity/neonatal unit discharge. INTERVENTIONS: Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine and benzodiazepines. MAIN OUTCOME MEASURES: During quiet sleep, the infants were switched from breathing room air to 15% oxygen and changes in minute volume were assessed. RESULTS: The SM infants had a greater mean increase (p=0.028, p=0.034, respectively) and a greater magnitude of decline (p<0.001, p=0.018, respectively) in minute volume than the S infants and the controls. The rate of decline in minute volume was greater in the SM infants (p=0.008) and the S infants (p=0.011) compared with the controls. CONCLUSIONS: Antenatal substance misuse and smoking affect the infant's ventilatory response to a hypoxic challenge.

The Utility of the Swine Model to Assess Biological Rhythms and Their Characteristics during Different Stages of Residence in a Simulated Intensive Care Unit: A Pilot Study.

The purpose of this pilot study was to explore the utility of the mammalian swine model under simulated intensive care unit (sICU) conditions and mechanical ventilation (MV) for assessment of the trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and gas exchange (GE). Data were collected prospectively with an observational time-series design to describe and compare circadian rhythms of selected study variables in four swine mechanically ventilated for up to seven consecutive days. We derived the circadian (total variance explained by rhythms of τ between 20 and 28 h)/ultradian (total variance explained by rhythms of τ between 1 and <20 h) bandpower ratio to assess the robustness of circadian rhythms, and compare findings between the early (first 3 days) and late (subsequent days) sICU stay. All pigs exhibited statistically significant circadian rhythms (τ between 20 and 28 h) in CBT, respiratory rate and peripheral oxygen saturation, but circadian rhythms were detected less frequently for sedation requirement, spontaneous minute volume, arterial oxygen tension, arterial carbon dioxide tension and arterial pH. Sedation did not appear to mask the circadian rhythms of CBT, PM and GE. Individual subject observations were more informative than group data, and provided preliminary evidence that (a) circadian rhythms of multiple variables are lost or desynchronized in mechanically ventilated subjects, (b) robustness of circadian rhythm varies with subject morbidity and (c) healthier pigs develop more robust circadian rhythm profiles over time in the sICU. Comparison of biological rhythm profiles among sICU subjects with similar severity of illness is needed to determine if the results of this pilot study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from MV.

Evaluation of N95 filtering facepiece respirator efficiency with cyclic and constant flows.

An increasing demand for protecting workers against harmful inhalable ultrafine particles (UFPs), by means of filtering facepiece respirators (FFRs), necessitates assessing the efficiency of FFRs. This article evaluates the penetration of particles, mostly in the ultrafine range, through one model of N95 FFRs exposed to cyclic and constant flows, simulating breathing for moderate to heavy work loads. The generated particles were poly-dispersed NaCl, within the range of 10-205.4 nm. The tests were performed for several cyclic flows, with mean inhalation flows (MIFs) ranging from 42 to 360 L/min, and constant flows with the same range. The measurements were based on filter penetration and did not consider particle leakage. With the penetrations recorded for the selected constant and cyclic flows, the worst-case scenario penetrations at the most penetrating particle size (MPPS) were obtained. The MPPS penetrations measured with the cyclic and constant flows equivalent to minute volume, MIF and peak inhalation flow (PIF) of the cyclic flows were then compared. It was indicated that the constant flows equivalent to the minute volume or PIF of the cyclic flow could not accurately represent the penetration of the corresponding cyclic flow: the constant flow equal to the minute volume of the cyclic flow significantly underestimated the MPPS penetration of the corresponding cyclic flow, while the constant flow equal to the PIF of the cyclic flow overestimated it. On the other hand, for the constant flow equal to the MIF of the cyclic flow, the MPPS penetrations were almost equal for both the constant and cyclic flows, for the lower flow rates (42 to 170 L/min). For higher flow rates (230 to 360 L/min), however, the MPPS penetration was exceeded under the constant flows, compared with the corresponding cyclic flows. It was therefore concluded that the constant flow equal to the MIF of the cyclic flow could better predict the results of corresponding cyclic flow, since it could provide the MPPS penetrations (worst-case scenario) equal to or greater than the MPPS penetrations of the cyclic flow.

Delivery of sevoflurane to dogs using a Stephens anaesthetic machine.

OBJECTIVE: To investigate the sevoflurane concentrations produced within the Stephens anaesthetic machine circuit (vaporizer in-circle system) at different fresh gas flow rates (FGFRs), temperatures, vaporizer settings and vaporizer sleeve positions when used to anaesthetize dogs of different body sizes. STUDY DESIGN: Experimental non-blinded studies. ANIMALS: Eighteen mixed breed dogs, weights 4-39 kg. METHODS: Anaesthetic induction with propofol was followed by maintenance with sevoflurane in oxygen via the Stephens anaesthetic machine. In study 1, the vaporizer setting, temperature and circuit FGFRs were altered with the vaporizer sleeve down (n = 3), or in separate experiments, up (n = 3). Delivered (Fi'SEVO) and expired sevoflurane concentrations were recorded. Study 2 determined the vaporizer settings (sleeve up) required to achieve predetermined multiples of minimal alveolar concentration (MAC) of Fi'SEVO when sevoflurane was delivered to dogs (n = 12) of different bodyweights and at different FGFRs. RESULTS: Delivered concentrations of sevoflurane were sufficient to maintain anaesthesia in all dogs, regardless of bodyweight, FGFR, vaporizer temperature and sleeve position. Fi'SEVO increased with increasing temperature, when the vaporizer sleeve was down, when vaporizer setting was increased and when FGFR was decreased. As the FGFR increased or the dog's bodyweight decreased, higher vaporizer settings were required to produce the same Fi'SEVO. The median Stephens vaporizer settings to achieve an Fi'SEVO of 1.3 MAC ranged from 4.3 to 5.0 for a small dog (1-10 kg), 2.5 to 5.6 for a medium dog (15-25 kg) and 2.5 to 3.5 for a large dog (30-40 kg), depending on the FGFR. CONCLUSION AND CLINICAL RELEVANCE: The Stephens anaesthetic machine can deliver to dogs, weighing 4 kg and above, concentrations of sevoflurane sufficient or in excess of that required to maintain anaesthesia, at temperatures from 10 to 35 °C, FGFRs of 1 to 5 times the patient's estimated metabolic oxygen requirement and at any vaporizer sleeve position.

Inhalation toxicity of soman vapor in non-anesthetized rats: a preliminary assessment of inhaled bronchodilator or steroid therapy.

Respiratory toxicity, injury and treatment following vapor inhalational exposure to the chemical warfare nerve agent (CWNA) soman (GD) were examined in non-anesthetized rats. This study exposed male Sprague-Dawley rats (250-300g) to 520, 560, 600, 825 or 1410mg×min/m(3) of soman in a customized head-out inhalation system. Signs of CWNA-induced cholinergic crises were observed in all soman-exposed animals. The LCt50 of vaporized soman as determined by probit analysis was 593.1mg×min/m(3). All animals exposed to 825 and 1410mg×min/m(3) developed severe convulsions and died within 4-8min post-exposure. Edema measured by wet/dry weight ratio of the left lung lobe increased in a dose-dependent manner in all soman-exposed animals. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase (AChE) activities were inhibited dose-dependently in soman-exposed groups at 24h. A significant increase in total BAL protein was observed in soman-exposed animals at all doses. AChE activity was inhibited in lung and whole brain tissues in all soman-exposed animals. Histopathological analysis of the lungs of animals exposed to 600mg×min/m(3) of soman revealed prominent morphological changes including alveolar histiocytosis, hemorrhage and inflammation consisting of neutrophilic exudate. Exposure of animals to 600mg×min/m(3) of soman followed by treatment with two actuations for 10s of Combivent (21µg of ipratropium bromide and 120µg of albuterol sulfate) and Symbicort (80µg budesonide and 4.5µg formoterol) by inhalation into a modified metered dose inhaler (MDI) 10min post-exposure resulted in increased minute volume, but did not decrease mortality. These results indicate that inhalation exposure to soman vapor causes acute respiratory toxicity and injury in untreated, un-anesthetized rats and that inhalation treatment with Combivent or Symbicort did improve the respiratory outcomes, but did not influence lethality.

Assessment of the respiratory sensitization potential of proteins using an enhanced mouse intranasal test (MINT).

There remains a need for a simple and predictive animal model to identify potential respiratory sensitizers. The mouse intranasal test (MINT) was developed to assess the relative allergic potential of detergent enzymes, however, the experimental endpoints were limited to evaluation of antibody levels. The present study was designed to evaluate additional endpoints (serum and allergic antibody levels, pulmonary inflammation and airway hyperresponsiveness (AHR)) to determine their value in improving the predictive accuracy of the MINT. BDF1 mice were intranasally instilled on days 1, 3, 10, 17 and 24 with subtilisin, ovalbumin, betalactoglobulin, mouse serum albumin or keyhole limpet hemocyanin; challenged with aerosolized methacholine or the sensitizing protein on day 29 to assess AHR, and sacrificed on day 29 or 30. Under the conditions of this study, evaluation of AHR did not improve the predictive power of this experimental model. Allergic antibody responses and IgG isotype characterization proved to be the most sensitive and reliable indicators of the protein allergenic potential with BAL responses providing additional insight. These data highlight that the evaluation of the respiratory sensitization potential of proteins can be best informed when multiple parameters are evaluated and that further improvements and refinements of the assay are necessary.