A model of respiratory syncytial virus (RSV) infection of infants in newborn lambs.

Many animal models have been established for respiratory syncytial virus (RSV) infection of infants with the purpose of studying the pathogenesis, immunological response, and pharmaceutical testing and the objective of finding novel therapies and preventive measures. This review centers on a neonatal lamb model of RSV infection that has similarities to RSV infection of infants. It includes a comprehensive description of anatomical and immunological similarities between ovine and human lungs along with comparison of pulmonary changes and immune responses with RSV infection. These features make the newborn lamb an effective model for investigating key aspects of RSV infection in infants. The importance of RSV lamb model application in preclinical therapeutic trials and current updates on new studies with the RSV-infected neonatal lamb are also highlighted.

Successful maintenance of key physiological parameters in preterm lambs treated with ex vivo uterine environment therapy for a period of 1 week.

BACKGROUND: Extremely preterm infants born at the border of viability (22-24 weeks' gestation) have high rates of death and lasting disability. Ex vivo uterine environment therapy is an experimental neonatal intensive care strategy that provides gas exchange using parallel membranous oxygenators connected to the umbilical vessels, sparing the extremely preterm cardiopulmonary system from ventilation-derived injury. OBJECTIVE: In this study, we aimed to refine our ex vivo uterine environment therapy platform to eliminate fetal infection and inflammation, while simultaneously extending the duration of hemodynamically stable ex vivo uterine environment therapy to 1 week. STUDY DESIGN: Merino-cross ewes with timed, singleton pregnancies were surgically delivered at 112-115 days of gestation (term is ∼150 days) and adapted to ex vivo uterine environment therapy (treatment group; n = 6). Physiological variables were continuously monitored; humerus and femur length, ductus arteriosus directional flow, and patency were estimated with ultrasound; serial blood samples were collected for hematology and microbiology studies; weight was recorded at the end of the experiment. Control group animals (n = 7) were euthanized at 122 days of gestation and analyzed accordingly. Bacteremia was defined by positive blood culture. Infection and fetal inflammation was assessed with white blood cell counts (including differential leukocyte counts), plasma and lung proinflammatory cytokine measurements, and lung histopathology. RESULTS: Five of 6 fetuses in the treatment group completed the 1-week study period with key physiological parameters, blood counts remaining within normal ranges, and no bacteremia detected. There were no significant differences (P > .05) in arterial blood oxygen content or lactate levels between ex vivo uterine environment therapy and control groups at delivery. There was no significant difference (P > .05) in birthweight between control and ex vivo uterine environment groups. In the ex vivo uterine environment group, we observed growth of fetal humerus (P < .05) and femur (P < .001) over the course of the 7-day experimental period. There was no difference in airway or airspace morphology or consolidation between control and ex vivo uterine environment animals, and there was no increase in the number of lung cells staining positive for T-cell marker CD3+. CONCLUSION: Five preterm lambs were maintained in a physiologically stable condition for 1 week with significant growth and without clinically significant bacteremia or systemic inflammation. Although substantial further refinement is required, a life support platform based around ex vivo uterine environment therapy may provide an avenue to improve outcomes for extremely preterm infants.

Stable Control of Physiological Parameters, But Not Infection, in Preterm Lambs Maintained on Ex Vivo Uterine Environment Therapy.

Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required.

A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model.

An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P < 0.01), and circuit resistance and minimal blood lactate levels were significantly lower in the parallel circuit group, compared with our previous single circuit group. Fetal physiological parameters remained stable until the conclusion of the experiments. In summary, parallelization of the AP system was associated with reduced circuit resistance and lactate levels and allowed preterm lamb fetuses to survive for a significantly longer period when compared with previous studies.

Minimal invasive lung support via umbilical vein with a double-lumen cannula in a neonatal lamb model: a proof of principle.

PURPOSE: Acute respiratory distress syndrome, with the need for invasive mechanical ventilation (MV) remains a major cause of neonatal mortality and morbidity. Although venovenous extracorporeal lung support (VV-ECLS) has become a standard of care procedure in neonatal patients with acute pulmonary failure there are no reports regarding the use of a double-lumen cannula for extracorporeal minimal invasive lung support via the umbilical vein. METHODS: A neonatal lamb model was used (n = 3). Umbilical vein was cannulated with a double-lumen catheter allowing venovenous extracorporeal gas exchange. Cannula was positioned with its tip in the right atrium. VV-ECLS was started and ventilation was stopped. Providing oxygenation and CO2 removal solely through VV-ECLS hemodynamics, blood gases were measured. RESULTS: Total VV-ECLS without MV was applied to all three neonatal lambs. Time on venovenous ECLS was 60, 120 and 120 min. Initial pCO2 was 60, 56 and 65 mmHg compared to 31, 32 and 32 mmHg at the end of VV-ECLS. Initial pO2 was 30, 27 and 26 mmHg compared to 22, 19 and 23 mmHg. Initial lactate was 5, 10 and 3.7 mmol/l compared to 13.3, 12.6 and 11.3 mmol/l at the end of VV-ECLS. MAP at baseline was 51, 52 and 65 mmHg compared to 36, 38 and 41 mmHg at the end of VV-ECLS. In all three lambs inotropes were admitted to maintain MAD >35 mmHg. CONCLUSION: Even without mechanical ventilation we were able to sufficiently remove pCO2 with our new minimal invasive VV-ECLS using a double-lumen catheter via the umbilical vein, supporting the idea of a lung protective strategy in neonatal acute respiratory failure. pO2 was measured 22, 19 and 23 mmHg, respectively, at the end of VV-ECLS, at least partially caused by recirculation phenomenon, which could possibly be improved by different cannula design. Inotropic support was necessary during VV-ECLS to achieve targeted MAD > 35 mmHg. While technically feasible, this new approach might allow further research in the field of extracorporeal lung support and therefore will follow the concept of a lung protective strategy in acute neonatal respiratory failure.

Aerosol Delivery of Palivizumab in a Neonatal Lamb Model of Respiratory Syncytial Virus Infection.

(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the "proof-of-principle" effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings.

Intact cord resuscitation in newborns with congenital diaphragmatic hernia: insights from a lamb model.

Introduction: Congenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics. Material and methods: At 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h. Results: CDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), p < 0.05, and right lung-to-body weight ratio of 8.2 (3.1), p < 0.05. They reached lower Vt/kg (tidal volume per kg) during the course of the resuscitation period with 1.2 (0.7) ml/kg at 10 min and 3 (1.65) ml/kg at 60 min (p < 0.05). Compliance of the respiratory system was lower in CDH lambs with 0.5 (0.3) ml/cmH2O at 60 min (p < 0.05) and 0.9 (0.26) ml/cmH2O at 120 min (p < 0.05). Differences between pre- and postductal SpO2 were higher with 15.1% (21.4%) at 20 min and 6.7% (14.5%) at 80 min (p < 0.05). CDH lambs had lower differences between inspired and expired oxygen fractions with 4.55% (6.84%) at 20 min and 6.72% (8.57%) at 60 min (p < 0.05). CDH lamb had lower left ventricle [2.73 (0.5) g/kg, p < 0.05] and lower right ventricle [0.69 (0.8), p < 0.05] to left ventricle ratio. Discussion: CDH lambs had significantly lower tidal volume than control lambs due to lower compliance of the respiratory system and higher airway resistance. These respiratory changes are characteristic of CDH infants and are associated with higher mortality rates. CDH lambs also exhibited pulmonary hypertension, pulmonary hypoplasia, and left ventricle hypoplasia, consistent with observations in human newborns. To conclude, our lamb model successfully provides a reliable representation of CDH and can be used to study its pathophysiology and potential interventions.

Chronic in utero mitral inflow obstruction unloads left ventricular volume in a novel late gestation fetal lamb model.

Objective: The in utero no flow/no grow hypothesis postulates that reduced inflow of blood into the left ventricle due to a stenotic mitral valve could lead to ventricular hypoplasia and hypoplastic left heart syndrome. This has been demonstrated in chick embryos, but less so in large animals. We investigated the impact of mitral obstruction on left and right ventricular growth in fetal lambs. Methods: Twelve pregnant ewes, most bearing twins, were instrumented at 119 ± 1 days gestational age. Carotid artery and jugular vein catheters, an ascending aorta flow probe, and a left atrial deflated balloon catheter were implanted into 1 fetus (left atrial balloon group), and the twin remained an uninstrumented control. The balloon was inflated gradually over 8 days until net antegrade aortic flow was eliminated. Fetal transesophageal echocardiography was performed at the time of surgery and just before termination in both groups. Results: Terminal fetal body weights were comparable between groups. Terminal heart/body weight ratio was higher in left atrial balloon group fetuses (6.9 ± 0.8 g/kg) compared with controls (5.9 ± 0.6 g, P = .0126). The left ventricular/right ventricular weight ratio was 24% (P = .0077) lower in left atrial balloon group fetuses than in controls. Left ventricular/heart weight (0.24 ± 0.04 g/g vs 0.30 ± 0.04 g/g, P = .0009), left ventricular end-diastolic volume (2.3 ± 0.7 mL vs 7.1 ± 0.8 mL; P = .0012), and left ventricular end-systolic volume (1.01 mL [0.95-1.95 mL] vs 3.38 mL [3.28-3.57 mL], P = .0042) were lower in left atrial balloon group fetuses compared with controls. Right ventricular weight (g/kg), right ventricular end-diastolic volume, and right ventricular end-systolic volume were similar between groups. Conclusions: In this late-gestation fetal lamb model, in utero obstruction of mitral inflow slowed left ventricular growth and caused right ventricular remodeling.

Acquisition of endoscopic nasal surgery skills with a lamb's head model.

OBJECTIVES: To evaluate the acquisition of surgical skills by otolaryngology residents and established the minimum number of dissections of a lamb's model to be performed before practicing on human patients. METHODS: Nineteen second-year otolaryngology residents performed ten dissections each, five on each nasal cavity, always practicing the same three surgical procedures on the lamb model. Each student's training lasted 2-months, and the entire training intervention lasted 4-years, over four generations of residents. All dissections were recorded and were selected at random for examination by two independent otolaryngology surgeons, who were otherwise not involved in the research. Assessment of the 190 dissections used an instrument validated for surgical training of medical residents. RESULTS: To a 1% significance level, statistical analysis revealed increased performance and satisfactory results were observed after the sixth dissection. Furthermore, after the eighth dissection, skill acquisition was relevant and sustained. CONCLUSION: Training in endoscopic nasal surgery on a lamb's head model improves surgical skills and handling of surgical instruments. Our results showed the relevance of the lamb model for training in otolaryngology surgery, impacting on patient safety.

A Novel Agnostic Respiratory Stimulant as a Treatment for Apnea of Prematurity: A Proof-of-Concept Study.

AIM/OBJECTIVE: ENA-001 is a novel selective antagonist of large-conductance BK (big potassium) channels located in the carotid bodies, where they act as chemoreceptors that sense low arterial oxygen levels and establish a feedback loop to brainstem nuclei responsible for initiating spontaneous breathing and maintaining adequate oxygen to tissues. ENA-001 attenuates respiratory depression induced by a variety of chemical agents, essentially "agnostic" to the precipitating drug (e.g., opioid(s), benzodiazepine, alcohol, or propofol). But it had not been tested against respiratory depression resulting from a physiological cause, such as apnea of prematurity (AOP). This proof-of-principle study used a well-described animal model (premature lamb) to test the effectiveness of ENA-001 in the setting of an under-developed respiratory control system, similar to that in human AOP. MATERIALS AND METHODS: A set of twin lambs was delivered prematurely via caesarian section at 135 ± 2 d gestational age (GA). An arterial catheter was connected to a transducer for pressure monitoring and a venous catheter was connected to a pump for continuous infusion of 5% dextrose in water (D5W). Lambs were to receive four mechanical breaths for lung recruitment and then started on continuous positive airway pressure (CPAP). After a stabilization period of 15 minutes, the protocol called for the first lamb to be started on continuous infusion of ENA-001, with ascending dose hourly (0.4, 1.1, 2.0, 12.0 mg/kg/hr), while the second lamb was to serve as a sham (D5W) control. At least 10 representative breaths free of artifact from motion or atypical breaths were recorded using a pulmonary function system designed for neonatal research. To maintain a stable plane of anesthesia, repeat doses of fentanyl (1 µg IM) were given as needed based on blood pressure response to stimulation. RESULTS: Two male lambs were delivered. Unexpectedly, neither lamb exhibited a drive for spontaneous breathing. Each required manual ventilation, with a complete absence of spontaneous effort. Despite the poor prognosis owing to the absence of ventilatory effort, continuous infusion of the first dose of ENA-001 was started 20 minutes after birth. The test animal continued to require manual ventilation, which was continued for an additional 10 minutes. An intravenous (IV) bolus of ENA-001 was given. Nearly instantaneously following the delivery of the IV bolus, the lamb began breathing spontaneously and did not require manual intervention for the remainder of the study. The sham animal was delivered approximately an hour following the test animal. As with the test animal, the sham animal lacked spontaneous breathing efforts. A decision was made to manually ventilate for 30 minutes to match the course for the test animal. At the 30-minute time point, an IV bolus infusion of ENA-001 was delivered. Nearly instantaneously following the delivery of the IV bolus, the lamb began breathing spontaneously. After several minutes, the spontaneous breathing efforts abated, and manual ventilation was resumed. The animal was then sacrificed for tissue harvest. CONCLUSION: These results suggest that ENA-001 might be an effective therapy, alone or as a co-medication, for the treatment of AOP. They further suggest that ENA-001 might have broader applications in situations of neurological ventilatory insufficiency.

Feasibility Study of Catheter-Based Interventions for Anisotropic Expanded Polytetrafluoroethylene Cardiovascular Conduits in a Growing Lamb Model.

BACKGROUND: Cardiovascular repair in children often requires implant of conduits which do not have growth potential and will require reoperation. In the current study we sought to determine the feasibility of catheter-based interventions of anisotropic conduits inserted as interposition grafts in the main pulmonary artery (MPA) of growing lambs. METHODS: Lambs underwent interpositional implant of either an anisotropic expanded polytetrafluoroethylene (ePTFE) (Test) conduit or conventional PTFE (Control) conduit. In the postoperative period, lambs were anesthetized and underwent catheter-based interventions consisting of hemodynamic and angiographic data collection, balloon dilation and/or stenting of the conduit at 3, 6 or 9 month postoperative time point. RESULTS: At 3 months, control lambs showed significant increases in right ventricular pressures and trans-conduit gradients in comparison to test lambs. Test conduit diameters were significantly larger compared to controls due to spontaneous radial expansion of the anisotropic conduit. Balloon dilation of test conduits at 3 and 6 months showed a reduction in RV pressure and statistically significant improvement in the RV outflow tract gradient as well as significant increase in graft diameter, compared to both control and pre-dilation conditions. Furthermore, the test conduit diameter increased significantly compared to the pre-balloon and control conditions at each time point. Necropsy of test conduits showed no evidence of tears, perforations, or clot and smooth interiors with well-healed anastomoses. CONCLUSIONS: Anisotropic conduits implanted as interposition grafts in the MPA show spontaneous expansion, and can safely and effectively undergo catheter-based interventions, with significant increases in graft diameter occurring after balloon dilation.

Anisotropic Polytetrafluoroethylene Cardiovascular Conduits Spontaneously Expand in a Growing Lamb Model.

BACKGROUND: Insertion of conduits from the right ventricle (RV) to the pulmonary artery (PA) is a commonly used technique for repair of congenital heart defects. The vast majority of infants and children will require reoperation and/or re-intervention to replace the conduit. Some children may require multiple reoperations, with the risk of death and morbidity increasing significantly with each subsequent operation. We evaluated the feasibility and performance of a relatively novel anisotropic conduit for cardiovascular repair in the growing lamb model. MATERIALS AND METHODS: Lambs were allocated into a control (n = 3) or test (n = 4, anisotropic) conduit group. Control conventional polytetrafluoroethylene (PTFE) conduits or test anisotropic expanded PTFE (ePTFE) based test conduits measuring 10-11 mm in diameter were sewn as interpositional grafts in the main pulmonary artery (MPA) and followed up to 6 months. Clinical and echocardiographic evaluations were performed monthly with hemodynamic and angiographic assessment at 3 and 6 months. RESULTS: Control conduits did not expand, all 3 animals developed one or more adverse events including tachypnea, ascites, inappetence, lethargy, and mortality due to severe right heart failure and significantly higher peak trans-conduit gradients (48.5 ± 5.1 p = 0.02). The test conduits spontaneously expanded up to 14.8 ± 0.8 mm in diameter, no adverse events were observed in any animals and trans-conduit gradients were significantly lower (27.0 ± 8.3, p = 0.02). CONCLUSIONS: Anisotropic ePTFE conduits can be safely implanted in growing lambs with stable hemodynamics. This spontaneously expanding anisotropic conduit may represent a novel approach to congenital heart repairs that would avoid the need for reoperation or multiple operations.

Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study.

OBJECTIVE: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. DESIGN: Prospective animal study. SETTING: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia. SUBJECTS: Four weaned Border-Leicester/Suffolk lambs at 5 months of age. INTERVENTIONS: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. MEASUREMENTS AND MAIN RESULTS: Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 µm, range = 0.54-5.41µm) and the AeroNeb Go® (3.07 ± 1.56 µm, range = 0.86-10 µm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. CONCLUSIONS: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.

Gestational Age Influences the Early Microarchitectural Changes in Response to Mechanical Ventilation in the Preterm Lamb Lung.

Background: Preterm birth is associated with abnormal lung architecture, and a reduction in pulmonary function related to the degree of prematurity. A thorough understanding of the impact of gestational age on lung microarchitecture requires reproducible quantitative analysis of lung structure abnormalities. The objectives of this study were (1) to use quantitative histological software (ImageJ) to map morphological patterns of injury resulting from delivery of an identical ventilation strategy to the lung at varying gestational ages and (2) to identify associations between gestational age-specific morphological alterations and key functional outcomes. Method: Lung morphology was compared after 60 min of a standardized ventilation protocol (40 cm H2O sustained inflation and then volume-targeted positive pressure ventilation with positive end-expiratory pressure 8 cm H2O) in lambs at different gestations (119, 124, 128, 133, 140d) representing the spectrum of premature developmental lung states and the term lung. Age-matched controls were compared at 124 and 128d gestation. Automated and manual functions of Image J were used to measure key histological features. Correlation analysis compared morphological and functional outcomes in lambs aged ≤128 and >128d. Results: In initial studies, unventilated lung was indistinguishable at 124 and 128d. Ventilated lung from lambs aged 124d gestation exhibited increased numbers of detached epithelial cells and lung tissue compared with 128d lambs. Comparing results from saccular to alveolar development (120-140d), lambs aged ≤124d exhibited increased lung tissue, average alveolar area, and increased numbers of detached epithelial cells. Alveolar septal width was increased in lambs aged ≤128d. These findings were mirrored in the measures of gas exchange, lung mechanics, and molecular markers of lung injury. Correlation analysis confirmed the gestation-specific relationships between the histological assessments and functional measures in ventilated lambs at gestation ≤128 vs. >128d. Conclusion: Image J allowed rapid, quantitative assessment of alveolar morphology, and lung injury in the preterm lamb model. Gestational age-specific patterns of injury in response to delivery of an identical ventilation strategy were identified, with 128d being a transition point for associations between morphological alterations and functional outcomes. These results further support the need to develop individualized respiratory support approaches tailored to both the gestational age of the infant and their underlying injury response.

Pregnant sheep develop hypoxaemia during short-term anaesthesia for caesarean delivery.

Short-term anaesthesia of the pregnant ewe may be required for caesarean delivery of a preterm foetus within a research protocol. The aim of this study was to evaluate and compare the acid-base and haematological status of the ewe and foetus at the time of surgical delivery by collecting maternal and foetal arterial blood samples. Fifteen date-mated singleton-pregnant merino cross ewes at 122.0 (±0.5) days of gestation were anaesthetised with a combination of midazolam (0.5 mg/kg) and ketamine (10 mg/kg) by intravenous injection. A subarachnoid injection of lidocaine (60 mg) was given to desensitise the caudal abdomen. Supplemental oxygen was not provided, and an endotracheal tube was not placed in the ewe's trachea. The development of maternal respiratory acidosis (hypercapnia) and hypoxaemia was anticipated. Samples of arterial blood for blood gas analyses were collected simultaneously from the radial artery of the ewe and the umbilical artery of the foetus immediately after delivery. The results from the maternal blood samples were within the normal range for pH, partial pressure of carbon dioxide in arterial blood (PaCO2), base excess, glucose, lactate, haematocrit and haemoglobin concentration. The maternal partial pressure of oxygen in arterial blood (PaO2) revealed hypoxaemia: 45.2 (41.1-53.4) mmHg. Foetal arterial blood gas analysis revealed hypoxaemia (15.0 ± 3.1 mmHg) and hypoglycaemia (0.1 (0.1-1.1) mmol/L). The benefit of providing supplemental oxygen and/or placing an endotracheal tube must be carefully weighed against the benefit of saving time when prompt delivery of the foetus is planned. In this study the pregnant ewe developed severe hypoxaemia, and this abnormality may have contributed to a low foetal PaO2.

Acquisition of endoscopic nasal surgery skills with a lamb's head model

Abstract Objectives: To evaluate the acquisition of surgical skills by otolaryngology residents and established the minimum number of dissections of a lamb's model to be performed before practicing on human patients. Methods: Nineteen second-year otolaryngology residents performed ten dissections each, five on each nasal cavity, always practicing the same three surgical procedures on the lamb model. Each student's training lasted 2-months, and the entire training intervention lasted 4-years, over four generations of residents. All dissections were recorded and were selected at random for examination by two independent otolaryngology surgeons, who were otherwise not involved in the research. Assessment of the 190 dissections used an instrument validated for surgical training of medical residents. Results: To a 1% significance level, statistical analysis revealed increased performance and satisfactory results were observed after the sixth dissection. Furthermore, after the eighth dissection, skill acquisition was relevant and sustained. Conclusion: Training in endoscopic nasal surgery on a lamb's head model improves surgical skills and handling of surgical instruments. Our results showed the relevance of the lamb model for training in otolaryngology surgery, impacting on patient safety. Level of evidence: 2.