Computational Analysis of Polymeric Biodegradable and Customizable Airway Stent Designs.

The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient's lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.

Computational fluid dynamics comparison of the upper airway velocity, pressure, and resistance in cats using an endotracheal tube or a supraglottic airway device.

Intoduction: In veterinary medicine, airway management of cats under general anesthesia is performed with an endotracheal tube (ETT) or supraglottic airway device (SGAD). This study aims to describe the use of computational fluid dynamics (CFD) to assess the velocities, pressures, and resistances of cats with ETT or SGAD. Methods: A geometrical reconstruction model of the device, trachea, and lobar bronchi was carried out from computed tomography (CT) scans that include the head, neck, and thorax. Twenty CT scans of cats under general anesthesia using ETT (n = 10) and SGAD (n = 10) were modeled and analyzed. An inspiratory flow of 2.4 L/min was imposed in each model and velocity (m/s), general and regional pressures (cmH2O) were computed. General resistance (cmH2O/L/min) was calculated using differential pressure differences between the device inlet and lobar bronchi. Additionally, regional resistances were calculated at the device's connection with the breathing circuit (region A), at the glottis area for the SGAD, and the area of the ETT exit (bevel) (region B) and the device itself (region C). Results: Recirculatory flow and high velocities were found at the ETT's bevel and at the glottis level in the SGAD group. The pressure gradient (Δp) was more enhanced in the ETT cases compared with the SGAD cases, where the pressure change was drastic. In region A, the Δp was higher in the ETT group, while in regions B and C, it was higher in the SGAD group. The general resistance was not statistically significant between groups (p = 0.48). Higher resistances were found at the region A (p = <0.001) in the ETT group. In contrast, the resistance was higher in the SGAD cases at the region B (p = 0.001). Discussion: Overall, the provided CT-based CFD analysis demonstrated regional changes in airway pressure and resistance between ETT and SGAD during anesthetic flow conditions. Correct selection of the airway device size is recommended to avoid upper airway obstruction or changes in flow parameters.

Salbutamol transport and deposition in healthy cat airways under different breathing conditions and particle sizes.

Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the non-cooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 µm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%-2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.

Management of Osteoarthritis and Joint Support Using Feed Supplements: A Scoping Review of Undenatured Type II Collagen and Boswellia serrata.

In the multimodal management of osteoarthritis (OA) in recent decades, the use of feed supplements to maintain joint cartilage has been advocated. The aim of this scoping review is to present the results found in the veterinary literature on the use of undenatured type II collagen and Boswellia serrata in dogs, specifically its use in dogs with clinical signs of OA, healthy dogs after intense exercise or dogs with diseases that predispose the individual to OA. For this purpose, a literature review was carried out using the electronic databases PubMed, Web of Science and Google Scholar, from which a total of 26 records were included in this review: fourteen evaluating undenatured type II collagen, ten evaluating Boswellia serrata and two evaluating the combination of undenatured type II collagen and Boswellia serrata. The review of the records showed that undenatured type II collagen decreases the clinical signs associated with OA, improving the general clinical state with a reduction in the degree of lameness and increase in physical activity or mobility. Evaluating the response to supplementation with Boswellia serrata alone is complicated due to the limited publication of studies and variations in the purity and compositions of the products used, but in general terms, its combination with other feed supplements produces benefits by relieving pain and reducing the clinical signs of OA in dogs. The combination of both in the same product provides results similar to those obtained in undenatured type II collagen studies. In conclusion, undenatured type II collagen and Boswellia serrata are considered a valid option for the multimodal approach to the management of OA and for improving activity during intense exercise, but more studies are needed to conclude whether or not it prevents OA in dogs.

Evaluation of lung ventilation distribution using electrical impedance tomography in standing sedated horses with capnoperitoneum.

OBJECTIVE: To determine changes in distribution of lung ventilation with increasing intra-abdominal pressure (IAP) from carbon dioxide (CO2) insufflation in standing sedated horses. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of six healthy adult horses. METHODS: Each horse was sedated with acepromazine, detomidine and butorphanol and sedation maintained with a detomidine infusion. The horse was restrained in a stocks system and a 32 electrode electrical impedance tomography (EIT) belt was wrapped around the thorax at the fifth-sixth intercostal space. EIT images and arterial blood samples for PaO2 and PaCO2, pH and lactate concentration were obtained during capnoperitoneum at 0 (baseline A), 5, 8 and 12 mmHg as IAP increased and at 8, 5, 0 (baseline B) mmHg as IAP decreased. At each IAP, after a 2 minute stabilization period, EIT images were recorded for ≥ 2 minutes to obtain five consecutive breaths. Statistical analysis was performed using anova for repeated measures with Geisser-Greenhouse correction and a Tukey's multiple comparison test for parametric data. The relationship between PaO2 and the center of ventilation in the ventral-dorsal (CoV-VD) and right-left (CoV-RL) directions or total impedance change as a surrogate for tidal volume (ΔZVT) were tested using linear regression analysis. Significance was assumed when p ≤ 0.05. RESULTS: There were no significant changes in CoV-VD, CoV-RL, PaO2, PaCO2, lactate concentration, pH, heart rate and respiratory rate with targeted IAP. There was a significant decrease in ΔZVT compared with baseline A at 5 mmHg IAP as IAP was increased. CONCLUSIONS AND CLINICAL RELEVANCE: Capnoperitoneum causes a significant decrease in ΔZVT in standing sedated horses with increasing IAP.

Salbutamol Transport and Deposition in the Upper and Lower Airway with Different Devices in Cats: A Computational Fluid Dynamics Approach.

Pressurized metered-dose inhalers (pMDI) with or without spacers are commonly used for the treatment of feline inflammatory airway disease. During traditional airways treatments, a substantial amount of drugs are wasted upstream of their target. To study the efficiency of commonly used devices in the transport of inhaled salbutamol, different computational models based on two healthy adult client-owned cats were developed. Computed tomographic images from one cat were used to generate a three-dimensional geometry, and two masks (spherical and conical shapes) and two spacers (10 and 20 cm) completed the models. A second cat was used to generate a second model having an endotracheal tube (ETT) with and without the same spacers. Airflow, droplet spray transport, and deposition were simulated and studied using computational fluid dynamics techniques. Four regions were evaluated: device, upper airways, primary bronchi, and downstream lower airways/parenchyma ("lung"). Regardless of the model, most salbutamol is deposited in devices and/or upper airways. In general, particles reaching the lung varied between 5.8 and 25.8%. Compared with the first model, pMDI application through the ETT with or without a spacer had significantly higher percentages of particles reaching the lung (p = 0.006).

Dexmedetomidine-methadone-ketamine versus dexmedetomidine-methadone-alfaxalone for cats undergoing ovariectomy.

OBJECTIVE: To compare the duration, quality of anaesthesia and analgesia, and quality of recovery of dexmedetomidine and methadone combined with either ketamine or alfaxalone. STUDY DESIGN: Randomized, prospective clinical trial. ANIMALS: A group of 44 healthy client-owned cats presenting for ovariectomy. METHODS: Cats were randomly assigned to one of the two treatment groups: DAM (n=22), which was administered intramuscularly (IM) dexmedetomidine (15 µg kg-1), methadone (0.3 mg kg-1) and alfaxalone (3 mg kg-1), and DKM (n=22), which was administered IM dexmedetomidine (15 µg kg-1), methadone (0.3 mg kg-1) and ketamine (3 mg kg-1). During anaesthesia, heart rate, respiratory rate and systolic arterial pressure were measured every 5 minutes. Cats that moved or had poor muscle relaxation were administered an additional 1 mg kg-1 of either alfaxalone (DAM) or ketamine (DKM) intravenously (IV). In cases of increased autonomic responses to surgical stimulation, fentanyl (2 µg kg-1) was administered IV. At the end of the surgery, atipamezole (75 µg kg-1) was administered IM, and the times to both sternal recumbency and active interaction were recorded. Quality of recovery was evaluated with a simple descriptive scale. The UNESP-Botucatu multidimensional composite pain scale and a visual analogue scale were used to evaluate postoperative analgesia at the return of active interaction and 1, 2 and 3 hours later. RESULTS: The additional anaesthesia and rescue fentanyl requirements were similar between groups. The quality of recovery was better in the DAM group than in the DKM group [simple descriptive scale scores: 0 (0-1) and 1 (0-3), respectively; p=0.002]. Postoperative pain scores decreased progressively over time in both groups, with no significant differences (p=0.08) between them. CONCLUSIONS AND CLINICAL RELEVANCE: Both protocols provided comparable quality of anaesthesia and analgesia and were suitable for cats undergoing ovariectomy. In combination with methadone and dexmedetomidine, alfaxalone and ketamine showed comfortable and reliable recoveries.

Comparison of intratesticular lidocaine, sacrococcygeal epidural lidocaine and intravenous methadone in cats undergoing castration: a prospective, randomized, investigator-blind clinical trial.

OBJECTIVE: The objective of this study was to compare three analgesic protocols for feline castration. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-nine client-owned cats. METHODS: Cats were injected with intramuscular (IM) dexmedetomidine (15 µg kg-1) and alfaxalone (3 mg kg-1) and assigned randomly to one of three treatment groups. Group ITL (n = 15) were administered intratesticular 2% lidocaine (0.05 mL each testicle), group SCL (n = 15) a sacrococcygeal epidural injection of 2% lidocaine (0.1 mL kg-1) and group IVM (n = 19) intravenous (IV) methadone (0.3 mg kg-1), before surgery. Cardiorespiratory variables were recorded. In case of autonomic nociceptive response, IV fentanyl (2 µg kg-1) was administered. During recovery, time from IM atipamezole (75 µg kg-1, administered at the end of surgery) to sternal recumbency and to active interaction was recorded. Quality of recovery was assessed using a simple descriptive scale. Postoperative analgesia was evaluated using a visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale (MCPS) at return of active interaction and then 1, 2 and 3 hours later. RESULTS: The three analgesic protocols were comparable in terms of intraoperative fentanyl and propofol requirement. Cardiorespiratory variables stayed within normal ranges in the majority of the cases, although group IVM had the lowest intraoperative respiratory rate (p = 0.0009). No differences were detected between groups in UNESP-Botucatu MCPS scores (p = 0.21). However, group ITL showed higher visual analogue scale score than group IVM (p = 0.001). Four cats enrolled in group ITL, as well as three of group SCL and one of group IVM, required rescue analgesics before the completion of pain assessment. CONCLUSIONS AND CLINICAL RELEVANCE: Intratesticular and sacrococcygeal epidural lidocaine injections could be regarded as good alternatives to systemic opioids in cats undergoing castration, although the benefits of these techniques seem to be of shorter duration than IV methadone.

Pharmacokinetic Study of Paclitaxel Concentration after Drug-Eluting Balloon Angioplasty in the Iliac Artery of Healthy and Atherosclerotic Rabbit Models.

PURPOSE: To assess whether the presence of an atherosclerotic lesion may alter the deposition kinetics of paclitaxel on the arterial wall after drug-eluting balloon (DEB) angioplasty, as well as paclitaxel concentrations in serum and in the recovered balloons. MATERIALS AND METHODS: Three New Zealand White rabbit models were created: an atheroma group (arterial mechanical injury and hyperlipidic diet; group A), a prelesional group (fat arterial infiltration, hyperlipidic diet; group B), and a control healthy group (group C). Forty-five animals underwent DEB angioplasty in the iliac artery. Arteries and serum samples were analyzed by liquid chromatography/tandem mass spectrometry at 1, 24, 48, 72, and 96 hours (arteries) and at 1, 6, 12, and 24 hours (serum). Recovered balloons were analyzed by UV chromatography. Histologic and statistical analyses were also performed. RESULTS: Group A showed significantly higher arterial paclitaxel concentrations in the first hour after DEB angioplasty (632.05 ng/mg ± 125.75 in group A vs 179.55 ng/mg ± 45.64 and 168.54 ng/mg ± 83.48 in groups B and C, respectively; P < .05). Paclitaxel was undetectable in serum at 24 hours in all groups, but the amount was significantly higher (P < .05) in group B at 1, 6, and 12 hours. The paclitaxel amount in navigated balloons from group A was significantly lower than in other groups (P < .05). CONCLUSIONS: Paclitaxel concentration in an atherosclerotic lesion model immediately after DEB angioplasty is nearly fourfold higher than in a healthy artery. Paclitaxel remains in the bloodstream longer when a universal state of fat arterial infiltration is achieved. These findings could have clinical implications, as studies testing commercial drug-eluting devices on healthy animals may be underestimating paclitaxel arterial uptake.