Pediatric Animal Model Research Articles

Increased Farnesoid X Receptor agonism in frontal cortex is associated with neuronal loss in a pig model of pediatric non-alcoholic fatty liver disease

Clinical studies suggest a link between non-alcoholic fatty liver disease (NAFLD) and neurodegeneration, but the mechanisms connecting both pathologies remain unknown. Rodent models of liver failure have shown neurological decline to be associated with increased bile acid (BA) levels and BA-activated farnesoid X receptor (FXR) signaling in the brain, which may disrupt brain’s cholesterol metabolism and promote neuronal death. We have previously established a pediatric animal model of NAFLD by feeding juvenile Iberian pigs a diet high in fat and fructose (HFF) for 10 weeks. The aim of this study was to determine whether BAs and FXR gene expression were increased in the frontal cortex (FC) of NAFLD pigs, and whether these changes were associated with neuronal loss. Eighteen 15-day-old Iberian pigs were assigned to receive for 10 weeks either a control (CON) or a HFF diet. FC was collected for immunohistochemistry, metabolomics, and transcriptomics analyses. Functional enrichment analyses were performed on differentially expressed genes to identify Gene Ontology (GO) terms using the Database for Annotation, Visualization, and Integrated Discovery. All HFF-fed pigs developed NAFLD. Immunostaining of mature neurons with NeuN was lower in FC of HFF compared with CON (P ≤ 0.05), whereas total BA levels increased (P ≤ 0.05) in FC of HFF-fed pigs. Brain levels of cholic and conjugated deoxycholic acids, which are FXR agonists, increased ( P ≤ 0.05) in HFF compared with CON. Conversely, tauroursodeoxycholic acid, which has strong FXR-antagonistic effect and has been shown to exert neuroprotective functions, was decreased (P ≤ 0.001) in HFF and was positively correlated with NeuN staining intensity (R2 = 0.623; P ≤ 0.001). Expression of FC genes encoding FXR, BA synthetic enzymes sterol 24- and 27-hydroxylases, and BA transporters Na+-taurocholate cotransporting polypeptide, organic anion transporting polypeptide, and organic solute transporters alpha and beta did not differ between groups. GO terms associated with Wnt/β-catenin pathway, which promotes neuronal survival and neurogenesis, were downregulated in HFF-fed pigs ( P ≤ 0.05), whereas mitochondrial respiratory chain complex and mitochondrion increased in HFF compared with CON ( P ≤ 0.01). In conclusion, increased BA levels and FXR agonism in frontal cortex of NAFLD pigs was associated with dysregulated Wnt/β-catenin signaling pathway and neuronal loss. California State University Agriculture Research Institute (grants 58873 and 58913), California Polytechnic State University internal funding programs Baker/Koob, RSCA, Frost, BiOWiSH Technologies, Hilmar Ingredients, and Acorn Seekers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Lactobacillus salivarius ssp. salicinius SA-03 Supplementation on Reversing Phthalate-Induced Asthma in Mice.

Probiotics may protect against asthma. We want to investigate whether probiotics can reverse the adverse effects of phthalate exposure on asthma. We selected the female offspring of BALB/c mice, born from pregnant female mice fed with diethylhexyl phthalate (DEHP). They were continuously administrated DEHP and Lactobacillus salivarius ssp. salicinius SA-03 when they were 5 weeks old, and ovalbumin (OVA) for asthma induction started at 6 weeks for 32 days. The mice were divided into four groups (n = 6/group): 1. control group (C), 2. OVA/DEHP group (OD), 3. OVA/DEHP/probiotics low-dose group (ODP-1X), and OVA/DEHP/probiotics high-dose group (ODP-5X). We found that the administration of probiotics significantly reduced the asthma severity of the mice, as well as serum IgE and IL-5. In the ODP-5X group, the proportion of CD4+ cells in the lung was reduced, whereas IL-10 in serum and CD8+ cells in BALF were increased. In histopathology, the ODP group showed reduced infiltration of inflammatory cells, bronchial epithelial cell hyperplasia, and tracheal mucus secretion. These results might indicate that high-dose probiotics may affect anti-inflammatory cytokines and reduce asthma-relative indicators. The above results may provide evidence that high-dose probiotics supplementation might play a modulating role in DEHP causes of allergic asthma in the pediatric animal model.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbondioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded.Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

Pediatric Animal Model of Extracorporeal Cardiopulmonary Resuscitation after Prolonged Circulatory Arrest.

Congenital heart disease (CHD) is the most prevalent congenital malformation, with about one million births impacted worldwide per year. Comprehensive investigation of this disease requires appropriate and validated animal models. Piglets are commonly used for translational research due to their analogous anatomy and physiology. This work aimed to describe and validate a neonatal piglet model of cardiopulmonary bypass (CPB) with circulatory and cardiac arrest (CA) as a tool for studying severe brain damage and other complications of cardiac surgery. In addition to including a list of materials, this work provides a roadmap for other investigators to plan and execute this protocol. After experienced practitioners performed several trials, the representative results of the model demonstrated a 92% success rate, with failures attributed to small piglet size and variant vessel anatomy. Furthermore, the model allowed practitioners to select from a wide variety of experimental conditions, including varying times in CA, temperature alterations, and pharmacologic interventions. In summary, this method uses materials readily available in most hospital settings, is reliable and reproducible, and can be widely employed to enhance translational research in children undergoing heart surgery.

Ultrasound-Guided Selective Bronchial Intubation: A Feasibility Study in Pediatric Animal Model.

ObjectiveSelective one-lung ventilation used to optimize neonatal and pediatric surgical conditions is always a demanding task for anesthesiologists, especially during minimally invasive thoracoscopic surgery. This study aims to introduce an ultrasound-guided bronchial intubation and exclusion technique in a pediatric animal model.MethodsSeven rabbits were anesthetized and airway ultrasound acquisitions were done.ResultsTracheal tube progression along the trachea to the right bronchus and positioning of the bronchial blocker in the left bronchus were successfully done with consistent ultrasound identification of relevant anatomical structures.ConclusionThe study provided a new application of ultrasound in airway management. More advanced experimental studies are needed since this technique has the potential for translation to pediatric anesthesia.

Effects of airway management and tidal volume feedback ventilation during pediatric resuscitation in piglets with asphyxial cardiac arrest

To compare the effect on the recovery of spontaneous circulation (ROSC) of early endotracheal intubation (ETI) versus bag-mask ventilation (BMV), and expiratory real-time tidal volume (VTe) feedback (TVF) ventilation versus without feedback or standard ventilation (SV) in a pediatric animal model of asphyxial cardiac arrest. Piglets were randomized into five groups: 1: ETI and TVF ventilation (10 ml/kg); 2: ETI and TVF (7 ml/kg); 3: ETI and SV; 4: BMV and TVF (10 ml/kg) and 5: BMV and SV. Thirty breaths-per-minute guided by metronome were given. ROSC, pCO2, pO2, EtCO2 and VTe were compared among groups. Seventy-nine piglets (11.3 ± 1.2 kg) were included. Twenty-six (32.9%) achieved ROSC. Survival was non-significantly higher in ETI (40.4%) than BMV groups (21.9%), p = 0.08. No differences in ROSC were found between TVF and SV groups (30.0% versus 34.7%, p = 0.67). ETI groups presented lower pCO2, and higher pO2, EtCO2 and VTe than BMV groups (p < 0.05). VTe was lower in TVF than in SV groups and in BMV than in ETI groups (p < 0.05). Groups 1 and 3 showed higher pO2 and lower pCO2 over time, although with hyperventilation values (pCO2 < 35 mmHg). ETI groups had non significantly higher survival rate than BMV groups. Compared to BMV groups, ETI groups achieved better oxygenation and ventilation parameters. VTe was lower in both TVF and BMV groups. Hyperventilation was observed in intubated animals with SV and with 10 ml/kg VTF.

Effect of ventilation rate on recovery after cardiac arrest in a pediatric animal model.

AimsTo assess the impact of two different respiratory rates in hemodynamic, perfusion and ventilation parameters in a pediatric animal model of cardiac arrest (CA).MethodsAn experimental randomized controlled trial was carried out in 50 piglets under asphyxial CA. After ROSC, they were randomized into two groups: 20 and 30 respirations per minute (rpm). Hemodynamic, perfusion and ventilation parameters were measured 10 minutes after asphyxia, just before ROSC and at 5, 15, 30 and 60 minutes after ROSC. Independent medians test, Kruskal-Wallis test and χ2 test, were used to compare continuous and categorical variables, respectively. Spearman’s Rho was used to assess correlation between continuous variables. A p-value <0.05 was considered significant.ResultsArterial partial pressure of carbon dioxide (PaCO2) was significantly lower in the 30 rpm group after 15 minutes (41 vs. 54.5 mmHg, p <0.01), 30 minutes (39.5 vs. 51 mmHg, p < 0.01) and 60 minutes (36.5 vs. 48 mmHg, p = 0.02) of ROSC. The percentage of normoventilated subjects (PaCO2 30–50 mmHg) was significantly higher in the 30 rpm group throughout the experiment. pH normalization occurred faster in the 30 rpm group with significant differences at 60 minutes (7.40 vs. 7.34, p = 0.02). Lactic acid levels were high immediately after ROSC in both groups, but were significantly lower in the 20 rpm group at 30 (3.7 vs. 4.7 p = 0.04) and 60 minutes (2.6 vs. 3.6 p = 0.03).ConclusionsThis animal model of asphyxial CA shows that a respiratory rate of 30 rpm is more effective to reach normoventilation than 20 rpm in piglets after ROSC. This ventilation strategy seems to be safe, as it does not cause hyperventilation and does not affect hemodynamics or cerebral tissue perfusion.

Toxicokinetic Studies in Piglets Reveal Age-Related Differences in Systemic Exposure to Zearalenone, Zearalenone-14-Glucoside, and Zearalenone-14-Sulfate.

Juveniles are considered as one of the most vulnerable population groups concerning mycotoxins and their modified forms. The weaning stage is a particularly vulnerable period in the life of mammals, reflected in intestinal and immune dysfunction. The current study investigated the toxicokinetic (TK) characteristics of zearalenone (ZEN), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S) in weaned (4-week-old) piglets, by means of oral and intravenous administration of equimolar doses, i.e., 331, 500, and 415 μg/kg bodyweight, respectively. Plasma and urine were sampled pre- and post-administration and were quantitatively analyzed for ZEN, ZEN14G, ZEN14S, and in vivo metabolites by liquid chromatography-high-resolution mass spectrometry. Tailor-made TK models were elaborated to process data. A statistical comparison of the results was performed with TK data obtained in a previously reported study in pigs of 8 weeks of age. Additionally, porcine plasma protein binding was determined to support TK findings. The TK results for ZEN, ZEN14G, and ZEN14S, obtained in 4- and 8-week-old pigs, revealed significant age-related differences, based on differences in intestinal permeability, body fat content, gastrointestinal transit time, and biotransformation, with a special emphasis on an increased absorbed fraction of ZEN14G, i.e., 94 vs 61% in 4- compared to 8-week-old pigs. Since the growing pig has been reported to be a suitable pediatric animal model for humans concerning TK processes, these results may contribute to refine the risk assessment concerning modified ZEN forms in juvenile animals and humans.

Ventilator-induced lung injury in children: a reality?

Mechanical ventilation (MV) is inextricably linked to the care of critically ill patients admitted to the paediatric intensive care unit (PICU). Even today, little evidence supports best MV practices for life-threatening acute respiratory failure in children. However, careful attention must be paid because this life-saving technique induces pulmonary inflammation that aggravates pre-existing lung injury, a concept that is known as ventilator-induced lung injury (VILI). The delivery of too large tidal volumes (Vt) (i.e., volutrauma) and repetitive opening and closure of alveoli (i.e., atelectrauma) are two key mechanisms underlying VILI. Despite the knowledge of these mechanisms, the clinical relevance of VILI in critically ill children is poorly understood as almost all of our knowledge has been obtained from studies in adults or experimental studies mimicking the adult critical care situation. This leaves the question if VILI is relevant in the paediatric context. In fact, limited paediatric experimental data showed that the use of large, supraphysiologic Vt resulted in less inflammation and injury in paediatric animal models compared to adult models. Furthermore, the association between large Vt and adverse outcome has not been confirmed and the issue of setting positive end-expiratory pressure (PEEP) to prevent atelectrauma has hardly been studied in paediatric clinical studies. Hence, even today, the question whether or not there VILI is relevant in pediatric critical remains to be answered. Consequently, how MV is used remains thus based on institutional preferences, personal beliefs and clinical data extrapolated from adults. This signifies the need for clinical and experimental studies in order to better understand the use and effects of MV in paediatric patients with or without lung injury.

Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model

Pediatric drug development, especially in disease areas that only affect children, can be stimulated by using juvenile animal models not only for general safety studies, but also to gain knowledge on the pharmacokinetic and pharmacodynamic properties of the drug. Recently, the conventional growing piglet has been suggested as juvenile animal model. However, more studies with different classes of drugs are warranted to make a thorough evaluation whether the juvenile pig might be a suitable preclinical animal model. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs in human. The present study determined the PK parameters, gastro-intestinal and renal safety of 5 mg/kg BW ibuprofen after single intravenous, single oral and multiple oral administration to each time eight pigs (four males, four females) aging 1, 4, 8 weeks and 6–7 months. Oral administration was performed via a gastrostomy button. A jugular catheter was used for intravenous administration and blood sampling. To assess NSAID induced renal toxicity, renal function was evaluated using iohexol and p-aminohippuric acid as markers for glomerular filtration rate and renal plasma flow, respectively. After the trial, necropsy and histology was performed to evaluate macroscopic and microscopic gastro-intestinal as well as renal lesions. Both enantiomers, R-ibuprofen and S-ibuprofen, were determined in plasma using an in-house developed and validated UHPLC-MS/MS method. Pharmacokinetic parameters were estimated using compartmental analysis. Clearance and volume of distribution of total ibuprofen and both enantiomers increased with age as was observed in human. The rate of stereochemical conversion decreased with age. Multiple oral dosing decreased the absolute oral bioavailability and maximum plasma concentration of R-ibuprofen and food consumption did not influence drug absorption. Based on the limited available pediatric literature, the current study might suggest the conventional pig as suitable animal model to evaluate NSAIDs for pediatric use.

Dual Calcium and Voltage Mapping Reveals Differences in Maturity of Excitation-Contraction Coupling in Young Rat Hearts

In the broad field of cardiology, pediatric research has lagged behind in establishing appropriate models to study the developing heart. Human cardiomyocytes exhibit a limited life span and immortalized cell lines lack physiologically relevant automaticity. Pediatric animal models include caveats related to action potential morphology, ion channel expression, and excitation-contraction coupling. Changes that occur in these parameters as the animal transition from neonate to adult are relatively unknown, especially as it may be translated to a human model. In quantifying the toxicological effect of plasticizer exposure in a pediatric population, we first sought to establish the limits of using hearts from developing neonatal rats as a viable model. This study aimed to quantify the advantages and limitations associated with using neonatal rat hearts as a model for pharmacology screening. The heart from rats ranging in age from 2 days old, up to adult were excised, and the aorta was cannulated. It was placed on a Langendorff system and retrograde perfused. Calcium and voltage sensitive dyes were used to stain the heart for imaging via a single sensor, single excitation, dual emission system. It was mechanically uncoupled with blebbistatin to eliminate motion artifacts. Compared with adults, isolated neonatal rat hearts displayed a longer action potential duration (APD80: adult= 61.28ms n=9, neonatal=109.4ms n=34, P<0.05) associated with delayed repolarization as also evidenced by an increased in triangulation. Calcium handling was also slower in the neonatal heart (Cad80: Adults: 126.8ms n=12, neonatal=170.1 n=30, P<0.05), likely due to immature expression and localization of key calcium handling proteins. The developing excitation-contraction coupling machinery will be further probed using pharmacological tools, and this newly established pediatric model will be used for toxicological screening.

Correction: Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

[This corrects the article DOI: 10.1371/journal.pone.0149013.].

Simian Immunodeficiency Virus Persistence in Cellular and Anatomic Reservoirs in Antiretroviral Therapy-Suppressed Infant Rhesus Macaques.

Worldwide, nearly two million children are infected with human immunodeficiency virus (HIV), with breastfeeding accounting for the majority of contemporary HIV transmissions. Antiretroviral therapy (ART) has reduced HIV-related morbidity and mortality but is not curative. The main barrier to a cure is persistence of latent HIV in long-lived reservoirs. However, our understanding of the cellular and anatomic sources of the HIV reservoir during infancy and childhood is limited. Here, we developed a pediatric model of ART suppression in orally simian immunodeficiency virus (SIV)-infected rhesus macaque (RM) infants, with measurement of virus persistence in blood and tissues after 6 to 9 months of ART. Cross-sectional analyses were conducted to compare SIV RNA and DNA levels in adult and infant RMs naive to treatment and on ART. We demonstrate efficient viral suppression following ART initiation in SIV-infected RM infants with sustained undetectable plasma viral loads in the setting of heterogeneous penetration of ART into lymphoid and gastrointestinal tissues and low drug levels in the brain. We further show reduction in SIV RNA and DNA on ART in lymphoid tissues of both infant and adult RMs but stable (albeit low) levels of SIV RNA and DNA in the brains of viremic and ART-suppressed infants. Finally, we report a large contribution of naive CD4+ T cells to the total CD4 reservoir of SIV in blood and lymph nodes of ART-suppressed RM infants that differs from what we show in adults. These results reveal important aspects of HIV/SIV persistence in infants and provide insight into strategic targets for cure interventions in a pediatric population.IMPORTANCE While antiretroviral therapy (ART) can reduce HIV replication, the virus cannot be eradicated from an infected individual, and our incomplete understanding of HIV persistence in reservoirs greatly complicates the generation of a cure for HIV infection. Given the immaturity of the infant immune system, it is critically important to study HIV reservoirs specifically in this population. Here, we established a pediatric animal model to simulate breastfeeding transmission and study SIV reservoirs in rhesus macaque (RM) infants. Our study demonstrates that ART can be safely administered to infant RMs for prolonged periods and that it efficiently controls viral replication in this model. SIV persistence was shown in blood and tissues, with similar anatomic distributions of SIV reservoirs in infant and adult RMs. However, in the peripheral blood and lymph nodes, a greater contribution of the naive CD4+ T cells to the SIV reservoir was observed in infants than in adults.

Abstract 494: Comparing Cardiac Dynamics Between Neonatal and Adult Rats

Background: In the broad field of cardiology, pediatric research has lagged behind in establishing appropriate models to study the developing heart. Human cardiomyocytes exhibit a limited life span and immortalized cell lines lack physiologically relevant automaticity. Pediatric animal models include caveats related to action potential morphology, ion channel expression, and excitation-contraction coupling. Changes that occur in these parameters as the animal transition from neonate to adult are relatively unknown, especially as it may be translated to a human model. In quantifying the toxicological effect of plasticizer exposure in a pediatric population, we first sought to establish the limits of using hearts from developing neonatal rats as a viable model. Objective: This study aimed to quantify the advantages and limitations associated with using neonatal rat hearts as a model for toxicological screening. Methods/Design: The heart from rats ranging in age from 2 days old, up to adult were excised, and the aorta was cannulated. It was placed on a Langendorff system and retrograde perfused. Calcium and voltage sensitive dyes were used to stain the heart for imaging. It was mechanically uncoupled with blebbistatin to eliminate motion artifacts and an ECG was recorded continuously. Results/Discussion: Preliminary results showed that compared to adult cohorts, neonatal rats displayed a longer action potential duration (APD80: adult= 85.9ms, neonatal=95.5ms, p=0.026), likely associated with delayed Ito expression. Likewise, calcium handling was also slower in the neonatal hearts as shown by the calcium imaging. (Cad80: Adults: 128.9ms, neonatal=138.8, p=.004) Without autonomic modulation, we observed an increase in heart rate from 320 to 350bpm between neonatal and adult populations which has been shown in vivo . The developing excitation contraction coupling machinery will be further probed for the mechanism behind these phenomena.

Abstract P-018: ANALYSIS OF CHEST COMPRESSIONS QUALITY DURING RESUSCITATION IN A PEDIATRIC ANIMAL MODEL AFTER ASPHYXIAL CARDIAC ARREST

Aims & Objectives: To analyze quality of chest compressions (CC) during resuscitation and its impact on the return of spontaneous circulation (ROSC) in a pediatric animal model of cardiac arrest (CA) using a real-time feedback-device. Methods Depth and rate of CC were measured with an accelerometer (ZOLL®) during resuscitation in an experimental model of asphyxial CA in piglets. Compression depth between 3.8 and 5 cm and a rate between 100 and 120 compressions per minute were considered optimal. Results CC quality was recorded in 19 piglets. Twelve of them (63.2%) achieved ROSC. Only 41.3% of CC were optimal regarding rate and depth. Compression depth was optimal in 48.9%, too deep in 43.2% and too shallow in 7.9%. CC rate was optimal in 80.3%, too fast in 4.6% and slow in 15.1%. Compressions were more shallow and faster in piglets who recovered spontaneous circulation than in those who didn´t (table 1). Optimal compressions (rate and depth) (52.7 ± 25% vs 21.7 ± 16.2% p=0.010) and optimal depth (61.9 ± 28.2% vs 26.5 ± 17% p=0.008) were associated with higher ROSC. Animals who suffered airway bleeding or thoracic injuries had received deeper CC after 3 minutes of CPR, p=0.006. There was a correlation between mean arterial pressure and quality of CC (table 2).Conclusions In this pediatric CA model, only 41.3% of chest compressions were optimal. Optimal quality of CPR was associated with higher survival. Excessive CC depth was associated with airway bleeding or thoracic injuries and increased mortality.

Abstract P-019: COMPARISON BETWEEN SYNCHRONIZED AND NON-SYNCHRONIZED VENTILATION AND BETWEEN GUIDED AND NON-GUIDED CHEST COMPRESSIONS DURING RESUSCITATION IN A PEDIATRIC ANIMAL MODEL AFTER ASPHYXIAL CARDIAC ARREST

Aims & Objectives: To compare between synchronized and non-synchronized bag-valve-mask ventilation (BVMV) with chest compression and between guided and non-guided chest compression (CC) with a real-time feedback-device in a pediatric animal model of asphyxial cardiac arrest (CA). Methods Experimental model of asphyxial CA in piglets. Piglets were randomized for cardiopulmonary resuscitation (CPR) into four groups according to BVMV (synchronized and non-synchronized with CC) and to CC feedback (with and without CC feedback accelerometer, ZOLL®): Group A, guided-CC and synchronized ventilation; B, guided-CC and non-synchronized ventilation; C, non-guided CC and synchronized ventilation; D, non-guided CC and non-synchronized ventilation. Systolic, diastolic and mean blood pressure (SBP, DBP and MBP), and return of spontaneous circulation (ROSC) were compared between all groups. Results 43 piglets (median weight 11.8 kg) were studied. Twenty (46.5%) achieved ROSC: group A 36.4%, group B 75%, group C 30% and group D 46.5% (p=0.13). Survival rates was higher in group B than in A+C+D (75% vs 35.5%, p=0.02). ROSC was higher with non-synchronized ventilation (B+D 59.1% vs A+C 33.3%, p=0.091) and with guided-CC (A+B 56.5% vs C+D 35%, p=0.16). BP after 3 minutes of resuscitation are shown in Table 1. Non-synchronized ventilation was associated with higher SBP and MBP. No significant differences were found regarding blood pressures between group B and the rest of groups.Conclusions In a pediatric animal model of CA, non-synchronized ventilation and guided CPR obtained significantly higher survival rates. Better SBP and MBP after 3 minutes of resuscitation were achieved with non-synchronized ventilation.

Hemodynamic Effects of Connection to Continuous Renal Replacement Therapy in a Pediatric Animal Model.

To assess the hemodynamic effects of connection to continuous renal replacement therapy (CRRT) in a pediatric experimental animal model. Prospective experimental study was performed using piglets between 2 and 3 months of age and 9-11 kg. CRRT with a PrismaflexR monitor and HF20 filter (surface of 0.2 m2 ) was started after monitoring and anesthetic induction with an initial blood flow at 20 mL/min with 10 mL/min increases every minute until the goal flow of 5 mL/kg/min was achieved. Heart rate, blood pressure, central venous pressure, cardiac index, and renal blood flow were registered at baseline, 5, 15, 30, 60, 120, 180, 240, and 360 min. IBM SPSS Statistics 20.0 package was used for analysis. A P value of <0.05 was considered statistically significant. Thirty-four piglets were studied. Blood pressure, cardiac output, and systemic vascular resistance significantly decreased 5-min after CRRT connection (mean arterial pressure from 85.5 to 70.8 mm Hg, P < 0.001, cardiac index from 3.6 to 3.3 L/min/m2 P = 0.024, and systemic vascular resistance index from 1759 to 1607 dyn.s/cm5 P = 0.012). No significant changes were found in renal blood flow or central venous pressure. All parameters gradually increased at 15 and 30 min after connection but complete recovery was never achieved. Connection to CRRT produces a significant decrease in arterial pressure, cardiac index, and peripheral vascular resistances in hemodynamically stable piglets.

Ventilator-induced lung injury: does it occur in children?

Mechanical ventilation is one of the most practiced interventions in the pediatric intensive care unit (PICU). Although unmistakable life-saving, it can also injury the lung, a process coined ventilator induced lung injury (VILI). To date, almost all of our knowledge VILI has been obtained from studies in adults or experimental studies mimicking the adult critical care situation. This leaves the question if VILI is of importance in the pediatric context. Pediatric clinical studies did not confirm an association between large tidal volume (Vt) and adverse outcome. In fact, the opposite has been shown. These same studies did show an association between high pressures and adverse outcome. Experimental data showed that the use of large, supraphysiologic Vt resulted in less inflammation and injury in pediatric animal models compared to adult models, suggesting an age-related susceptibility to VILI. However, the question whether or not there is an age-related susceptibility to VILI remains puzzling and unanswered. It is remarkable that one of the most practiced interventions such as pediatric MV is hardly supported by any scientific evidence but rather based on personal experience and data from adults. This signifies the need for clinical and experimental studies in order to better understand the use and effects of MV in pediatric patients with or without lung injury.

Different Respiratory Rates during Resuscitation in a Pediatric Animal Model of Asphyxial Cardiac Arrest.

AimsActual resuscitation guidelines recommend 10 respirations per minute (rpm) for advanced pediatric life support. This respiratory rate (RR) is much lower than what is physiological for children. The aim of this study is to compare changes in ventilation, oxygenation, haemodynamics and return of spontaneous circulation (ROSC) rates with three RR.MethodsAn experimental model of asphyxial cardiac arrest (CA) in 46 piglets (around 9.5 kg) was performed. Resuscitation with three different RR (10, 20 and 30 rpm) was carried out. Haemodynamics and gasometrical data were obtained at 3, 9, 18 and 24 minutes after beginning of resuscitation. Measurements were compared between the three groups.ResultsNo statistical differences were found in ROSC rate between the three RR (37.5%, 46.6% and 60% in the 10, 20 and 30 rpm group respectively P = 0.51). 20 and 30 rpm groups had lower PaCO2 values than 10 rpm group at 3 minutes (58 and 55 mmHg vs 75 mmHg P = 0.08). 30 rpm group had higher PaO2 (61 mmHg) at 3 minutes than 20 and 10 rpm groups (53 and 45 mmHg P = 0.05). No significant differences were found in haemodynamics or tissue perfusion between hyperventilated (PaCO2 <30 mmHg), normoventilated (30–50 mmHg) and hypoventilated (>50 mmHg) animals. PaO2 was significantly higher in hyperventilated (PaO2 153 mmHg) than in normoventilated (79 mmHg) and hypoventilated (47 mmHg) piglets (P<0.001).ConclusionsOur study confirms the hypothesis that higher RR achieves better oxygenation and ventilation without affecting haemodynamics. A higher RR is associated but not significantly with better ROSC rates.

A pediatric animal model to evaluate the effects of disuse on musculoskeletal growth and development

Prolonged immobilization in hospitalized children can lead to fragility fractures and muscle contractures and atrophy. The purpose of this study was to develop a lower-extremity disuse rabbit model with musculoskeletal changes similar to those observed in children subjected to prolonged immobilization. Six-week-old rabbits were randomly assigned to control (CTRL, n=4) or bilateral sciatic and femoral neurectomy (bSFN, n=4) groups. Trans-axial helical CT scans of each rabbit׳s hind limbs were acquired after eight weeks. The rabbits were then euthanized and the tibiae and calcanea were harvested from each rabbit. μCT imaging was performed on the tibiae and calcanea mid-diaphysis. Four-point bending, gas pycnometry, and ashing were then performed on each tibia. All comparisons reflect the differences between the bSFN and CTRL rabbits. Significant decreases in tibiae bone mineral density (≥9.41%, p≤0.006), axial rigidity (≥50.47%, p≤0.02), and soft tissue mass (55.25%, p=0.006) were observed from the trans-axial helical CT scans. The μCT results indicated significant detriments in tibia and calcaneus cortical thickness and bone volume fraction (p≤0.011). Significant changes in stiffness, yield load, ultimate load, and ultimate displacement (≥30.05%, p≤0.025) were observed from mechanical testing. These data indicate that limb disuse at a time of rapid musculoskeletal growth severely impairs muscle and bone development, reflecting the musculoskeletal complications observed in children with chronic medical conditions causing immobilization. Interventions to reduce these musculoskeletal complications in children are urgently needed. This disuse rabbit model will be useful in pre-clinical studies evaluating novel interventions for improving pediatric musculoskeletal health.