Rabbit Lung Research Articles

Suppression of pulmonary group B streptococcal proliferation and translocation by surfactants in ventilated near-term newborn rabbits.

The pathogenesis of neonatal group B Streptococcus (GBS) lung infection may be associated with surfactant dysfunction or deficiency. This study aimed to investigate the efficacy of surfactants on early postnatal GBS infection in ventilated newborn rabbit lungs. A near-term newborn rabbit model was established by intratracheal GBS instillation immediately at birth, followed by mechanical ventilation. At postnatal 1 h, a porcine surfactant was given intratracheally at 100 or 200 mg/kg. After 6 h, animals were euthanized, and lung and blood samples were collected for bacterial counting. Lung histopathology and messenger RNA (mRNA) expression of inflammatory mediators, surfactant proteins, and growth factors in lung tissue were assessed. The surfactants significantly suppressed (by >50%) pulmonary bacterial proliferation and systemic translocation, alleviated lung inflammatory injury, and improved alveolar expansion by morphometry, in favor of high-dose surfactants. Though the survival rate and lung mechanics were not improved, the surfactants significantly suppressed mRNA expression of proinflammatory mediators, while that for surfactant proteins and growth factors was differentially expressed, compared to the control and GBS infection groups. Exogenous surfactants may provide a therapeutic alternative for neonatal lung infection by suppressing pulmonary GBS proliferation and translocation into systemic circulation, alleviating inflammatory injury and regulating growth factor expression.

Fluorescent and Iodized Emulsion for Preoperative Localization of Pulmonary Nodules.

This study was conducted to develop a fluorescent iodized emulsion comprising indocyanine green (ICG) solution and lipiodol (ethiodized oil) and evaluate its feasibility for use in a clinical setting. ICG use for the preoperative localization of pulmonary nodules is limited in terms of penetration depth and diffusion. First, fluorescent microscopy was used to investigate the distribution of ICG-lipiodol emulsions prepared using different methods. The emulsions were injected in 15 lung lobes of 3 rabbits under computed tomography fluoroscopy guidance; evaluation with imaging and radiography was conducted after thoracotomy. Subsequently, the emulsions were used to preoperatively localize 29 pulmonary nodules in 24 human subjects, and wedge resections were performed using fluorescent imaging and C-arm fluoroscopy. The optimal emulsion of 10% ICG and 90% lipiodol mixed through 90 passages had even distribution and the highest signal intensity under fluorescent microscopy; it also had the best consistency in the rabbit lungs, which persisted for 24 hours at the injection site. In human subjects, the mean diameter of pulmonary nodules was 0.9 ± 0.4 cm, and depth from the pleura was 1.2 ± 0.8 cm. All emulsion types injected were well localized around the target nodules without any side effects or procedure-related complications. Wedge resection with minimally invasive approach was successful in all pulmonary nodules with a free resection margin. A fluorescent iodized emulsion prepared by mixing ICG with lipiodol enabled accurate localization and resection of pulmonary nodules.

Characterisation of Staphylococcus aureus strain causing severe respiratory disease in rabbits

<em>Staphylococcus aureus</em> is acknowledged as one of the important pathogens isolated from humans and animals. However, the <em>S. aureus</em> causing severe respiratory diseases in rabbits have not been well characterised. A <em>S. aureus</em> named FZHW001, isolated from the lungs of dead rabbits with severe respiratory disease, was characterised by artificial infection of rabbits, detection of virulence factors, multi-locus sequencing typing and antimicrobial susceptibility test. The FZHW001 infected rabbits showed identical respiratory symptoms to those of naturally infected ones, and the isolate could spread through directed contact among rabbits. The isolate was typed into clonal complex 121 and carried 7 of 13 tested virulence factors. Furthermore, the isolate was identified to be methicillin-susceptible <em>S. aureus</em> and was susceptible to 7 of 12 tested antibiotics. This study first describes the characteristics of <em>S. aureus</em> isolated from rabbits causing severe respiratory disease, which will help in further understanding the pathogenic mechanisms of <em>S. aureus</em> in rabbits.

Measurement of Regional 2D Gas Transport Efficiency in Rabbit Lung Using Hyperpolarized 129Xe MRI

While hyperpolarized xenon-129 (HXe) MRI offers a wide array of tools for assessing functional aspects of the lung, existing techniques provide only limited quantitative information about the impact of an observed pathology on overall lung function. By selectively destroying the alveolar HXe gas phase magnetization in a volume of interest and monitoring the subsequent decrease in the signal from xenon dissolved in the blood inside the left ventricle of the heart, it is possible to directly measure the contribution of that saturated lung volume to the gas transport capacity of the entire lung. In mechanically ventilated rabbits, we found that both xenon gas transport and transport efficiency exhibited a gravitation-induced anterior-to-posterior gradient that disappeared or reversed direction, respectively, when the animal was turned from supine to prone position. Further, posterior ventilation defects secondary to acute lung injury could be re-inflated by applying positive end expiratory pressure, although at the expense of decreased gas transport efficiency in the anterior volumes. These findings suggest that our technique might prove highly valuable for evaluating lung transplants and lung resections, and could improve our understanding of optimal mechanical ventilator settings in acute lung injury.

New Insight into the Development of the Respiratory Acini in Rabbits: Morphological, Electron Microscopic Studies, and TUNEL Assay.

This study investigated the histomorphological features of developing rabbit respiratory acini during the postnatal period. On the 1st day of postnatal life, the epithelium of terminal bronchiole consisted of clear cells which intercalated between few ciliated and abundant non-ciliated (Clara) cells. At this age, the rabbit lung was in the alveolar stage. The terminal bronchioles branched into several alveolar ducts, which opened into atria that communicated to alveolar sacs. All primary and secondary inter-alveolar septa were thick and showed a double-capillary network (immature septa). The primitive alveoli were lined largely by type-I pneumocytes and mature type-II pneumocytes. The type-I pneumocytes displayed an intimate contact with the endothelial cells of the blood capillaries forming the blood-air barrier (0.90 ± 0.03 µm in thickness). On the 3rd day, we observed intense septation and massive formation of new secondary septa giving the alveolar sac a crenate appearance. The mean thickness of the air-blood barrier decreased to reach 0.78 ± 0.14 µm. On the 7th day, the terminal bronchiole epithelium consisted of ciliated and non-ciliated cells. The non-ciliated cells could be identified as Clara cells and serous cells. New secondary septa were formed, meanwhile the inter-alveolar septa become much thinner and the air-blood barrier thickness was 0.66 ± 0.03 µm. On the 14th day, the terminal bronchiole expanded markedly and the pulmonary alveoli were thin-walled. Inter-alveolar septa become much thinner and single capillary layers were observed. In the 1st month, the secondary septa increased in length forming mature cup-shaped alveoli. In the 2nd month, the lung tissue grew massively to involve the terminal respiratory unit. In the 3rd month, the pulmonary parenchyma appeared morphologically mature. All inter-alveolar septa showed a single-capillary layer, and primordia of new septa were also observed. The thickness of the air-blood barrier was much thinner; 0.56 ± 0.16 µm. TUNEL assay after birth revealed that the apoptotic cells were abundant and distributed in the epithelium lining of the pulmonary alveoli and the interstitium of the thick interalveolar septa. On the 7th day, and onward, the incidence of apoptotic cells decreased markedly. This study concluded that the lung development included two phases: the first phase (from birth to the 14th days) corresponds to the period of bulk alveolarization and microvascular maturation. The second phase (from the 14th days to the full maturity) corresponds to the lung growth and late alveolarization.

Effect of temperature and time on the thanatomicrobiome of the cecum, ileum, kidney, and lung of domestic rabbits.

Knowledge of changes in the composition of microbial communities (microbiota) in tissues after death, over time, is critical to correctly interpret results of microbiologic testing from postmortem examinations. Limited information is available about postmortem changes of the microbiota and the associated microbial genes (microbiome) of internal organs in any species. We examined the effect of time and ambient temperature on the postmortem microbiome (thanatomicrobiome) of tissues typically sampled for microbiologic testing during autopsies. Twenty rabbits were euthanized and their bodies stored at 4°C or 20°C for 6 or 48 h. Ileum, cecum, kidney, and lung tissue were sampled. Bacterial DNA abundance was determined by RT-qPCR. Microbiome diversity was determined by 16S rRNA gene sequencing. By relative abundance of the microbiome composition, intestinal tissues were clearly separated from lungs and kidneys, which were similar to each other, over all times and temperatures. Only cecal thanatomicrobiomes had consistently high concentrations and consistent composition in all conditions. In lungs and kidneys, but not intestine, proteobacteria were highly abundant at specific times and temperatures. Thanatomicrobiome variation was not explained by minor subclinical lesions identified upon microscopic examination of tissues. Bacterial communities typically found in the intestine were not identified at extra-intestinal sites in the first 48 h at 4°C and only in small amounts at 20°C. However, changes in tissue-specific microbiomes during the postmortem interval should be considered when interpreting results of microbiologic testing.

Preparation and evaluation of tilmicosin microspheres and lung-targeting studies in rabbits

Tilmicosin (TMS) is a macrolide used extensively for pulmonary infections in clinical veterinary medicine. However, TMS has frequent administration and short elimination half-life. Therefore, tilmicosin–gelatine microspheres (TMS–GMS) were prepared by an emulsion-chemical cross-linking technique as a sustained-release formulation to extend drug half-life. The particle size distribution, in-vitro sustained-release properties, stability, and physical characteristics, as well as pharmacokinetic (PK) characteristics, were evaluated in rabbits.TMS–GMS were spherical in shape and had a mean diameter of 11.34±1.20μm; 95.65% of the microspheres varied in size from 5.0 to 25.0μm. Light and thermal stability tests indicated no significant changes in all observed indices. Importantly, compared to crude TMS, slower release of TMS from TMS–GMS was noted in drug release studies (in vitro). Pharmacokinetic (PK) characteristics were examined in the lung, liver, heart, kidney and muscle tissue of rabbits following IM injection of TMS–GMS or TMS-injection at a dose of 10mg/kg. The elimination half-life of TMS–GMS (59.21±0.21h) was longer than that of TMS-injection (38.56±0.13h) in the lung. The ratio of peak concentration (Ce) of TMS–GMS to TMS-injection was 2.19 (>1) in the lung, demonstrating the selectivity of TMS–GMS to target the lung compared to that of other tissues (Ce<1). Interestingly, the uptake value of TMS from TMS–GMS was 8.48 times higher in the lung than that for the TMS-injection, and was slightly higher than in the liver (1.85), heart (1.72), kidney (2.44) and muscle (2.79) tissues. TMS–GMS is a sustained-release formulation of TMS with potential to be used in veterinary clinical applications; possible benefits include lung-targeting and prolonged elimination half-life.

99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors.

PurposeSelective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA). We report a new composite consisting of 99mTc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.MethodsCarbon nanoparticles with an encapsulated core of 99mTc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation.ResultsWe report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99mTc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis.ConclusionWe describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT.

Rabbit lung hemorrhage induced by acoustic radiation force impulse in clinical settings

Background Acoustic radiation force impulse (ARFI) has recently become widespread in clinical practice as ultrasound elastography. However, the safety of the modality is yet to be confirmed. Although we have already reported the alveolar hemorrhage induced by ARFI on rabbit lung tissue, these experiments were conducted with much longer pulse duration (PD) compared with that in clinical use. Therefore, we introduced a new ARFI exposure system that can confirm a targeting focal spot on a B mode image and adjust a focal depth with a good alignment precision. This time, we conducted a series of animal experiments with the setup which is equivalent to the clinical condition. Methods 10 rabbits were anesthetized and placed in spine position. Tracheal intubation was performed to control ventilation. A focused 5.2 MHz linear probe that transmitted ARFI was placed in precordial and subcostal regions bilaterally and determined appropriate locations for exposure of the lung through two paths (transhepatic and transthoracic) respectively. Exposure settings were varied in the cases and included: mechanical index (MI) 0.6∼1.4, PD 0.3 or 1.0ms, pulse repetition time (PRT) 3s, exposure time 90s. One case was conducted with ultrasound contrast agent. After exposure, the lungs were removed for macrophotography and histopathologic study. Results A red spot was observed on the surface of the lung corresponding to the area of exposure in each animal (17 at transhepatic and 19 at transthoracic path out of 20 and 19 exposures respectively). The size of red spots varied from 2 mm to 22 mm. The damage was not aggravated with use of ultrasound contrast agent. Microscopic findings confirmed alveolar hemorrhage in each red spot. Discussion Ultrasound exposure has been known to induce lung injury in animal experiments. In this study, ARFI induced lung injury under the acoustic output regulation value of MI ( Conclusion Lung hemorrhage was induced under regulation value of MI and with shorter PD of 0.3ms equivalent to that in clinical use of ARFI. These results identify a potential risk of lung injury associated with the elastography when the lung is unintentionally exposed to ultrasound from the probe, especially for liver or breast imaging.

Experimental study on the pathological changes in lung of abdominal compartment syndrome model rabbits

To investigate the secondary pathological changes in lung of abdominal compartment syndrome (ACS). Twenty-five healthy adult clean New Zealand rabbits were randomly divided into control group (n = 5) and experimental group (n = 20) according to the random number table method. The experimental group was subdivided into two subgroups according to the observation time: 24 hours and 48 hours, with 10 rabbits in each subgroup. A high pressure liquid animal model of abdominal cavity was reproduced by water bag superposition pressurization. In the control group, the pressurized water bag did not inject liquid, and intra-abdominal pressure (IAP) was maintained at 0; while in the experimental group, pressurized water infusion was performed, and IAP was maintained at 25 mmHg (1 mmHg = 0.133 kPa). The rabbits in the control group were sacrificed at 48 hours, those in the experimental group were sacrificed at 24 hours and 48 hours respectively, and the lungs were harvested completely. The pathological changes were observed under light microscope after hematoxylin-eosin (HE) staining. In the control group, the activity of the rabbits was decreased, the food intake was decreased, and all the 5 animals survived; in the experimental group, the activity was decreased significantly, little food intake or not, the urine output was decreased significantly, and 1 rabbit died at 22, 27 and 37 hours respectively, and 17 survived. Light microscopy showed that there were terminal bronchioles and a large number of alveoli in the lung tissue of the control group, and small vessels dilated in the interstitium. In the experimental group, alveolar epithelial hyperplasia, alveolar septum of different sizes, alveolar fusion, alveolar septal bleeding, interstitial heart failure cells with phagocytosis of hemosiderin, bronchiolectasis, a large number of inflammatory cell infiltration near the bronchi, thrombosis in the blood vessels were found at 24 hours. A large number of erythrocyte and cellulose-like exudates were seen in the lumen of terminal bronchioles, alveolar dilatation and fusion were aggravated, and old hemorrhage in the lumen of the alveoli was observed, hemosiderosis containing hemosiderin was observed at 48 hours. ACS could cause severe lung injury and aggravate as time goes on.

Surgical technique for developing a rabbit model of congenital diaphragmatic hernia and tracheal occlusion

The surgical model of congenital diaphragmatic hernia (CDH) has been utilized in exploring treatments and innovative therapies, such as tracheal occlusion (TO). The rabbit is an excellent surgical model compared to others due to lower cost, ease of care, short gestational period, and large litter size. This model is also ideal in studying lung hypoplasia of CDH because rabbit lung development is most similar to humans as alveolarization begins prior to birth and continues post-natally. However, the surgical technique in creating a rabbit model of CDH is quite difficult and information is lacking on how to establish this model. Therefore, the aim of this paper is to describe:•Surgical technique in establishing a rabbit model of CDH and TO•Perioperative care for pregnant rabbit does

Pulmonary Microcirculation in Experimental Model of Pulmonary Thromboembolism under Conditions of α-Adrenoceptor Blockade

Changes in the pulmonary microcirculation in isolated perfused rabbit lungs during modeling of pulmonary thromboembolism were studied in control animals and against the background of α-adrenoceptors blockade with phentolamine. Intravenous injection of emboli to control animals was followed by an increase in pressure in the pulmonary artery, mean capillary hydrostatic pressure, capillary filtration coefficient, pulmonary vascular resistance, as well as precapillary and postcapillary resistances. Against the background of α-adrenoceptor blockade, the increase in most parameters was less pronounced than in control animals, while capillary filtration coefficient increased more drastically. Thus, adrenergic mechanisms are involved in the constrictor reactions of both arterial and venous pulmonary vessels under conditions of pulmonary thromboembolism.

Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung.

Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT. Laboratory animal investigation. European synchrotron radiation facility. Six New-Zealand White rabbits. The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; FIO2, 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 × 47.5 × 47.5 μm voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured. The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.35 ± 0.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 ± 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001). Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

Preventive effect of the phage VB-SavM-JYL01 on rabbit necrotizing pneumonia caused by Staphylococcus aureus

Staphylococcus aureus is one of the most important pathogens causing rabbit necrotizing pneumonia and brings huge economic losses to rabbit production. This study investigated the preventive effect of a phage on rabbit necrotizing pneumonia caused by S. aureus. S. aureus S6 was isolated from the lungs of rabbits suffering necrotizing pneumonia and identified. A novel phage named VB-SavM-JYL01 was isolated by using S. aureus S6 as a host and showed a broader host range than the phages GH15 and K. The genome of VB-SavM-JYL01 lacked bacterial virulence-, antibiotic resistance- and lysogenesis-related genes. A single intranasal administration of VB-SavM-JYL01 (3 × 109 PFU) could effectively improve the survival rate at 48 h to 90% (9/10) compared with the survival rate of 10% and 80% observed with the PBS or linezolid treatment, respectively. The bacterial count in the lungs of rabbits treated with the phage VB-SavM-JYL01 was 4.18 × 104 CFU/g at 24 h, which was significantly decreased compared to that of rabbits treated with PBS (7.38 × 107 CFU/g) or linezolid (3.12 × 105 CFU/g). The phage treatment significantly alleviated lung tissue damage. The levels of total proteins, Panton-Valentine leukocidin (PVL), alpha-toxin (Hla) and cytokines in the lungs of the rabbits treated with the phage were significantly lower than those of the rabbits treated with PBS and similar to those of the rabbits treated with linezolid. These data demonstrate the potential utility of phage as an alternative for preventing rabbit necrotizing pneumonia caused by S. aureus.

Volumetric but Not Time Capnography Detects Ventilation/Perfusion Mismatch in Injured Rabbit Lung.

Whereas time capnography (Tcap) is routinely displayed during mechanical ventilation, the volumetric representation (Vcap) is seldom used. We compared the diagnostic value of indices derived from Tcap and Vcap following ventilation to perfusion ratio () mismatch subsequent to experimentally induced acute respiratory distress syndrome (ARDS), and alveolar recruitment by elevating the positive end-expiratory pressure (PEEP). Lung injury was induced by iv lipopolysaccharide, whole lung lavage and injurious ventilation in anesthetized, mechanically ventilated rabbits (n = 26). Mainstream Tcap and Vcap were performed to assess normalized phase 2 (Sn2T, Sn2V) and phase 3 slopes (Sn3T, Sn3V) in the time and volumetric domains. Vcap was also used to estimate Enghoff’s physiological dead space (VDE). Lung oxygenation index (PaO2/FiO2) and intrapulmonary shunt (Qs/Qt) were derived from arterial and central venous blood gas samples. All measurements were made under baseline conditions, and, following lung injury, under moderate (6 cmH2O) and high PEEP levels (9 cmH2O). Lung injury deteriorated the PaO2/FiO2 (baseline vs. injured 466 ± 10.2 [95% confidence interval] vs. 77.3 ± 17.1 mmHg, p < 0.05) and compromised all mechanical parameters significantly, whereas Tcap parameters exhibited contradictory or inconsistent changes. Conversely, Vcap indices exhibited consistent changes and provided excellent diagnostic value in detecting lung-function deterioration subsequent to lung injury [area under the receiver operating characteristic (ROC) curve of 1.0 ± 0.0, 0.87 ± 0.22 and 0.86 ± 0.22 for VDE, Sn3V and Sn3V/Sn2V, respectively]. Elevated PEEP increased PaO2/FiO2 and decreased Qs/Qt, which was reflected only in the Vcap slope ratio (Sn3V/Sn2V, p < 0.05). Our findings demonstrate the limited value of Tcap to detect ventilation to perfusion ratio () mismatch, following severe lung injury. Conversely, indices derived from Vcap proved to be sensitive for detecting lung volume loss and alveolar recruitment. Therefore, promotion of Vcap is of paramount importance as a real-time, non-invasive, bedside monitoring modality to detect the development of and to follow-up the progression of lung injury in a model of ARDS.

Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging

The purpose of this study was to investigate a preclinical spectral photon-counting CT (SPCCT) prototype compared to conventional CT for pulmonary imaging. A custom-made lung phantom, including nodules of different sizes and shapes, was scanned with a preclinical SPCCT and a conventional CT in standard and high-resolution (HR-CT) mode. Volume estimation was evaluated by linear regression. Shape similarity was evaluated with the Dice similarity coefficient. Spatial resolution was investigated via MTF for each imaging system. In-vivo rabbit lung images from the SPCCT system were subjectively reviewed. Evaluating the volume estimation, linear regression showed best results for the SPCCT compared to CT and HR-CT with a root mean squared error of 21.3 mm3, 28.5 mm3 and 26.4 mm3 for SPCCT, CT and HR-CT, respectively. The Dice similarity coefficient was superior for SPCCT throughout nodule shapes and all nodule sizes (mean, SPCCT: 0.90; CT: 0.85; HR-CT: 0.85). 10% MTF improved from 10.1 LP/cm for HR-CT to 21.7 LP/cm for SPCCT. Visual investigation of small pulmonary structures was superior for SPCCT in the animal study. In conclusion, the SPCCT prototype has the potential to improve the assessment of lung structures due to higher resolution compared to conventional CT.

Evaluating the protective effects of vitamin E and selenium on hematology and liver, lung and uterus histopathology of rabbits with cypermethrin toxicity

The objective of this study was to determine the efficacy of vitamin E and selenium as protective agents against cypermethrin (CY)-induced toxicity by evaluating hematology parameters along with liver, lung and uterus histopathology of female rabbits. Thirty female rabbits were randomly divided into five equal groups with six animals in each group (designated A, B, C, D and E). Animals in group A were control animals that did not receive CY, vitamin E, nor selenium. Animals in groups B–E were injected intraperitoneally with CY at 75 mg/kg body weight once every5 days over a 32 day period, while animals in the control group received saline. Animals in group C were also given vitamin E (150 mg/kg b.wt) orally and animals in group D were given selenium (0.45 mg/kg b.wt) orally. Group E was given both vitamin E at a dose of 150 mg/kg and selenium at a dose of 0.45 mg/kg. In group B (CY only), the values of PCV were decreased at the 12th day of gestation when compared to group A. The mean value of PCV was significantly higher in group E on the 12 and 24th day when compared to the other groups. The mean values of hemoglobin (Hb) were not significantly different among groups on the 12th and 24th day of gestation. On the 12th day of the gestation period, there were nonsignificant differences in the total number of erythrocytes among all the groups. However, on the 24thdayof the gestation period, there was a significant decrease in the total number of erythrocytes in group B compared to the control group. Total leukocytes were also increased in the animals of group B on the 12th day of gestation, whereas the total leukocytes were increased on the 24th day of gestation in all groups (A–D) compared to control. Histopathological studies of tissues of liver, lungs and uterus revealed that CY altered the normal parenchyma of these tissues and this was partially ameliorated by the vitamin E and selenium treatments. In conclusion, combined use of vitamin E and selenium partially ameliorated the toxicity of CY in female rabbits.

Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair.

The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model. Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48h after injury. The post mortem was performed 3days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments. Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p < 0.001), as reflected by improved of structural changes such as thickness of the basement membrane, epithelium, mucosa and sub-mucosa regions. The airway inflammation score of both treatment groups revealed a significant reduction of inflammation and granulocyte infiltration at the peribronchiale and perivascular regions (p < 0.05). Administration of aerosolised MSCs alone was resulted in significant reduction in the levels of pro-inflammatory genes (IL-4 and TGF-β) while treatment with aerosolised MSC-pANGPT1 led to further reduction of various pro-inflammatory genes to the base-line values (IL4, TNF, MMP9 and TGF-β). Treatment with both aerosolised MSCs and MSC-pANGPT1 cells was also alleviated the number of airway inflammatory cells in the bronchoalveolar lavage (BAL) fluid and goblet cell hyperplasia. Our findings suggest that treatment with MSCs alone attenuated airway inflammation and structural changes of the airway. Treatment with MSC-pANGPT1 provided an additional effect in reducing the expression levels of various pro-inflammatory genes. Both of these treatment enhancing airway repair and therefore may provide a basis for the development of an innovative approach for the treatment and prevention of airway inflammatory diseases.

MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia.

Profiling of miR-200b expression and its targets (transforming growth factor [TGF]-β2 and ZEB2) in the surgical rabbit congenital diaphragmatic hernia (DH) model before and after tracheal occlusion (TO). Thirty-eight timed-pregnant rabbits had left DH creation on gestational day (GD) 23. On GD28, 17 randomly selected fetuses had TO. We harvested fetuses at GD23, GD28, or GD30. We calculated lung-to-body weight ratios, processed lungs for miR-200b in situ hybridization and real-time quantitative polymerase chain reaction, and evaluated effects on downstream targets TGF-β2 or ZEB2. We obtained 16 DH fetuses (n=7 GD28 and n=9 GD30), 13 TO fetuses (GD30), and 38 control fetuses (n=15 GD23, n=11 GD28, and n=12 GD30). Diaphragmatic hernia lungs were hypoplastic, and TO resulted in control lung-to-body weight ratio levels. Term miR-200b-3p levels were significantly upregulated in the hypoplastic compared with control ipsilateral lung (1.906±0.90 vs 0.7429±0.44) (P<.01). Fetal TO ipsilateral lungs displayed a variable miR-200b response on in situ hybridization and polymerase chain reaction, with levels similar to control and congenital DH lungs. The TGF-β2 was unchanged in hypoplastic and TO lungs, and ZEB2 tended to be reduced in TO compared with DH lungs (1.79 [0.4-2.9] vs 0.73 [0.5-1.4]). Hypoplastic fetal rabbit lungs display upregulation of miR-200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR-200b response.

Lung injury severity changes in response to different blast shock waves in rabbits

Objective To observe the effect of different explosion on rabbit lung injury and decide the death curve, so as to provide a reference for the prediction of lung injury. Methods Six healthy male New Zealand white rabbits with weight of 2.0-2.5 kg and age of (6±1)months were selected. The rabbits were put 0.5 m, 0.6 m, 0.7 m, 0.9 m, 1.0 m, and 1.2 m away from 90 g TNT to carry out the blast injury experiment. The characteristic parameters of blast shock wave and general lung injury were recorded. Based on the experimental results combined with theoretical analysis, the changes of rabbit lung injury depending on the explosion distance as well as the rabbit death curve were determined. Results After the 90 g TNT explosion, the peak overpressure of shock wave and the corresponding specific decreased quickly with the increase of explosion distance. The peak overpressure was 0.79 MPa and the specific was 82 Pa·s at the explosion distance of 0.5 m. The peak overpressure was 0.1 MPa and the specific was 34 Pa·s at the explosion distance of 1.2 m. The rabbits at 0.5 m and 0.6 m died, the rabbit at 0.7 m was severely injured, and the rabbits at 0.9 m, 1.0 m, and 1.2 m were slightly injured. The dependence of lung injury degree on the explosion distance under 90 g TNT explosion was established based on dimensional analysis theory. The lung injury degree was exponentially attenuated with the explosion distance: ϕ= (R/0.6)-5.64 (ϕ represented lung injury degree, and R represented the explosion distance). Considering the combined injury effects of peak overpressure of shock wave and its specific on rabbit lung, the death curve of rabbit was determined: (p-0.1)(I-59)=2.6(p represented peak overpressure, and I represented specific impulse). The criterion of overpressure-specific impulse was used to estimate the death of rabbit, and the death curve of rabbit was determined as (p-0.1)(I-59)=2.6(p represented peak overpressure and I represented specific impulse). The critical overpressure was 0.1 MPa and the critical specific was 59 Pa·s. Conclusions Under the explosion condition of 90 g TNT, the relationship between degree of lung injury in rabbits and explosion distance is established. Death curve of rabbits is determined based on the damage effect of shock wave peak overpressure and specific on the lungs of rabbits, which is significant for predicting the blast injury. Key words: Blast injuries; Lung injury; Rabbits; Injury prediction