Pediatric Porcine Model Research Articles

Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.

Adult and Pediatric Porcine Model of Acute Volume Overload.

This protocol describes an acute volume overload porcine model for adult Yorkshire pigs and piglets. Both swine ages undergo general anesthesia, endotracheal intubation, and mechanical ventilation. A central venous catheter and an arterial catheter are placed via surgical cutdown in the external jugular vein and carotid artery, respectively. A pulmonary artery catheter is placed through an introducer sheath of the central venous catheter. PlasmaLyte crystalloid solution is then administered at a rate of 100 mL/min in adult pigs and at 20 mL/kg boluses over 10 min in piglets. Hypervolemia is achieved either at 15% decrease in cardiac output or at 5 L in adult pigs and at 500 mL in piglets. Hemodynamic data, such as heart rate, respiratory rate, end-tidal carbon dioxide, fraction of oxygen-saturated hemoglobin, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, partial arterial oxygen pressure, lactate, pH, base excess, and pulmonary artery fraction of oxygen-saturated hemoglobin, are monitored during experimentation. Preliminary data observed with this model has demonstrated statistically significant changes and strong linear regressions between central hemodynamic parameters and acute volume overload in adult pigs. Only pulmonary capillary wedge pressure demonstrated both a linear regression and a statistical significance to acute volume overload in piglets. These models can aid scientists in the discovery of age-appropriate therapeutic and monitoring strategies to understand and prevent acute volume overload.

Pediatric Extracorporeal Cardiopulmonary Resuscitation: Development of a Porcine Model and the Influence of Cardiopulmonary Resuscitation Duration on Brain Injury.

Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group (P=0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4-7.4] versus CPR30: 7.5 [IQR 7.4-7.5], P=0.022), higher lactate (CPR60: 6.8 [IQR 6.8-11] versus CPR30: 4.2 [IQR 4.1-4.3] mmol/L; P=0.012), and higher ICP (CPR60: 19.3 [IQR 11.7-29.3] versus CPR30: 7.9 [IQR 6.7-9.3] mm Hg; P=0.037). Both groups had greater mitochondrial injury than shams (CPR60: P<0.001; CPR30: P<0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.

Imaging of White Matter Injury Correlates with Plasma and Tissue Biomarkers in Pediatric Porcine Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) causes significant white matter injury, which has been characterized by various rodent and human clinical studies. The exact time course of imaging changes in a pediatric brain after TBI and its relation to biomarkers of injury and cellular function, however, is unknown. To study the changes in major white matter structures using a valid model of TBI that is comparable to a human pediatric brain in terms of size and anatomical features, we utilized a four-week-old pediatric porcine model of injury with controlled cortical impact (CCI). Using diffusion tensor imaging differential tractography, we show progressive anisotropy changes at major white matter tracts such as the corona radiata and inferior fronto-occipital fasciculus between day 1 and day 30 after injury. Moreover, correlational tractography shows a large part of bilateral corona radiata having positive correlation with the markers of cellular respiration. In contrast, bilateral corona radiata has a negative correlation with the plasma biomarkers of injury such as neurofilament light or glial fibrillary acidic protein. These are expected correlational findings given that higher integrity of white matter would be expected to correlate with lower injury biomarkers. We then studied the magnetic resonance spectroscopy findings and report decrease in a N-acetylaspartate/creatinine (NAA/Cr) ratio at the pericontusional cortex, subcortical white matter, corona radiata, thalamus, genu, and splenium of corpus callosum at 30 days indicating injury. There was also an increase in choline/creatinine ratio in these regions indicating rapid membrane turnover. Given the need for a pediatric TBI model that is comparable to human pediatric TBI, these data support the use of a pediatric pig model with CCI in future investigations of therapeutic agents. This model will allow future TBI researchers to rapidly translate our pre-clinical study findings into clinical trials for pediatric TBI.

Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

ObjectiveCerebral mitochondrial dysfunction is a key mediator of neurologic injury following cardiac arrest (CA) and is regulated by the balance of fusion and fission (mitochondrial dynamics). Under stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion promotes oxidative phosphorylation efficiency. This study evaluates mitochondrial dynamics and content in brain tissue 24h after CA between two cardiopulmonary resuscitation (CPR) strategies. InterventionsPiglets (1 month), previously randomized to three groups: (1) Std-CPR (n=5); (2) HD-CPR (n=5; goal systolic blood pressure 90mmHg, goal coronary perfusion pressure 20mmHg); (3) Shams (n=7). Std-CPR and HD-CPR groups underwent 7min of asphyxia, 10min of CPR, and standardized post-resuscitation care. Primary outcomes: (1) cerebral cortical mitochondrial protein expression for fusion (OPA1, OPA1 long to short chain ratio, MFN2) and fission (DRP1, FIS1), and (2) mitochondrial mass by citrate synthase activity. Secondary outcomes: (1) intra-arrest haemodynamics and (2) cerebral performance category (CPC) at 24h. ResultsHD-CPR subjects had higher total OPA1 expression compared to Std-CPR (1.52; IQR 1.02–1.69 vs 0.67; IQR 0.54−0.88, p=0.001) and higher OPA1 long to short chain ratio than both Std-CPR (0.63; IQR 0.46−0.92 vs 0.26; IQR 0.26−0.31, p=0.016) and shams. Citrate synthase activity was lower in Std-CPR than sham (11.0; IQR 10.15–12.29 vs 13.4; IQR 12.28–15.66, p=0.047), but preserved in HD-CPR. HD-CPR subjects had improved intra-arrest haemodynamics and CPC scores at 24h compared to Std-CPR. ConclusionsFollowing asphyxia-associated CA, HD-CPR exhibits increased pro-mitochondrial fusion protein expression, preservation of mitochondrial mass, improved haemodynamics and superior neurologic scoring compared to Std-CPR. Institutional protocol numberIAC 16-001023.

Abstract 132: Cardiopulmonary Resuscitation with Chest Compressions During Sustained Inflations in a Pediatric Porcine Model - A Randomized Control Animal Trial

Background: Pediatric resuscitation guidelines recommend continuous chest compressions (CC) with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation (CPR) once an airway has been secured. However, the optimal CC technique remains unknown. Aim: To determine if CCs during sustained inflations (SI) improves return of spontaneous circulation (ROSC) of asphyxiated pediatric piglets compared to CCaV. Intervention and measurements: Piglets (age 20-23 days) were anesthetized, intubated, instrumented, and asphyxiated. Protocolized resuscitation was initiated when mean arterial blood pressure was &lt;25mmHg with bradycardia. Piglets (n=12/group) were randomized to receive CCaV resuscitation (CCaV group) according to the current resuscitation guidelines, or CC during SI (CC+SI group). The CC+SI group received a SI with a peak inflating pressure of 25 cmH 2 O for 30sec, CCs were provided at a rate of 100/min, and SI was interrupted after 30 sec for one second before a further 30sec SI was provided. CC and SI were continued until ROSC. Respiratory parameters, carotid blood flow, systemic artery pressures, and cerebral oxygenation were measured. Main results: Median (IQR) time to ROSC was significantly decreased in the CC+SI group compared to CCaV with 248 (41-346)sec vs. 720 (167-720)sec (p=0.049), respectively. CC+SI had a 100% higher rate of ROSC compared to CCaV with 10(83%) vs. 5(42%) (p=0.089), respectively. Piglets in the CC+SI group received a median (IQR) 3.5 (0-5.8) intravenous epinephrine boluses compared to 8.0 (1.8-11) in the CCaV group (p=0.123). Conclusions: Combining CC and SI significantly improved time to ROSC and survival in asphyxiated pediatric piglets when compared to the current standard of CCs with CCaV during pediatric CPR.

Cardiopulmonary resuscitation with chest compressions during sustained inflations in a pediatric porcine model – A randomized control animal trial

Cardiopulmonary resuscitation with chest compressions during sustained inflations in a pediatric porcine model – A randomized control animal trial

Abstract 130: Pediatric Cardiac Arrest: Adult Defibrillation Energies are Safe and Effective When Treating a Pediatric Porcine Model

Objective: When attempting defibrillation in an out-of-hospital pediatric patient, the use of a reduced energy is recommended by the resuscitation guidelines due to concerns surrounding potential myocardial damage. This study investigated the effectiveness (first shock success) and safety (myocardial damage) of using adult defibrillation energies in a pediatric model of cardiac arrest. Methods: Twelve piglets (9.5-25.5 kg; typical weight range of 1 to 8 year old children) were anaesthetized and VF was electrically induced. After 15 seconds of untreated VF, defibrillation was delivered using either Protocol A (adult energies; 150J) or Protocol B (pediatric energies; 75J). Following successful defibrillation, a 3 minute rest period was allowed for the heart to recover before VF was again induced. Blood samples were collected and analyzed for cardiac troponin I (cTnI). After 20 shocks were delivered, each animal remained anaesthetized and monitored for 6 hours. Results: A total of 240 shocks were delivered across both protocols with adult and pediatric energies providing comparable first shock success rates of 98.3% (116/118) and 96.6% (112/116). Prior to the induction of VF, Protocols A and B presented with equivalent median (IQR) levels of cardiac damage marker cTnI; 0.04 (0.02, 0.07) ng/ml ( n =6) and 0.05 (0.03, 0.08) ng/ml ( n =6), respectively. Comparable cTnI results were also observed upon completion of the defibrillation phase: Protocol A – 0.23 (0.12, 0.32) ng/ml; Protocol B – 0.20 (0.12, 0.27) ng/ml. There was 100% (12/12) survival after the 6 hour monitoring period with both protocols presenting similar cTnI: Protocol A – 0.32 (0.27, 0.55) ng/ml; Protocol B – 0.28 (0.20, 0.46) ng/ml. There were no clinically significant differences observed between the adult and pediatric defibrillation energy groups. Furthermore, histopathological evaluation revealed no discernible difference in cardiac damage between energy protocols. Conclusion: This study demonstrates that adult defibrillation energies are as effective in terminating VF and do not produce statistically higher levels of cTnI than pediatric defibrillation energies. These results suggest that adult defibrillation energies are appropriate for the treatment of pediatric cardiac arrest.

A hemodynamic-directed approach to pediatric cardiopulmonary resuscitation (HD-CPR) improves survival

AimMost pediatric in-hospital cardiac arrests (IHCAs) occur in ICUs where invasive hemodynamic monitoring is frequently available. Titrating cardiopulmonary resuscitation (CPR) to the hemodynamic response of the individual improves survival in preclinical models of adult cardiac arrest. The objective of this study was to determine if titrating CPR to systolic blood pressure (SBP) and coronary perfusion pressure (CoPP) in a pediatric porcine model of asphyxia-associated ventricular fibrillation (VF) IHCA would improve survival as compared to traditional CPR. MethodsAfter 7min of asphyxia followed by VF, 4-week-old piglets received either hemodynamic-directed CPR (HD-CPR; compression depth titrated to SBP of 90mmHg and vasopressor administration to maintain CoPP ≥20mmHg); or Standard Care (compression depth 1/3 of the anterior–posterior chest diameter and epinephrine every 4min). All animals received CPR for 10min prior to the first defibrillation attempt. CPR was continued for a maximum of 20min. Protocolized intensive care was provided to all surviving animals for 4h. The primary outcome was 4-h survival. ResultsSurvival rate was greater with HD-CPR (12/12) than Standard Care (6/10; p=0.03). CoPP during HD-CPR was higher compared to Standard Care (point estimate +8.1mmHg, CI95: 0.5–15.8mmHg; p=0.04). Chest compression depth was lower with HD-CPR than Standard Care (point estimate −14.0mm, CI95: −9.6 to −18.4mm; p<0.01). Prior to the first defibrillation attempt, more vasopressor doses were administered with HD-CPR vs. Standard Care (median 5 vs. 2; p<0.01). ConclusionsHemodynamic-directed CPR improves short-term survival compared to standard depth-targeted CPR in a porcine model of pediatric asphyxia-associated VF IHCA.

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

BackgroundHalf a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.ObjectiveTo determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Methods and ResultsFive-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5–7 (p≤0.001). There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2–19.7; p = 0.03). However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0–15.9; p<0.001) in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p<0.001), whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p<0.001) and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025).ConclusionsMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

Comparison of defibrillation efficacy between two pads placements in a pediatric porcine model of cardiac arrest

ObjectiveThe placement of defibrillation pads at ideal anatomical sites is one of the major determinants of transthoracic defibrillation success. However, the optimal pads position for ventricular defibrillation is still undetermined. In the present study, we compared the effects of two different pads positions on defibrillation success rate in a pediatric porcine model of cardiac arrest. MethodsEight domestic male pigs weighing 12–15kg were randomized to receive shocks using either the anterior–posterior (AP) or the anterior–lateral (AL) position with pediatric pads. Ventricular fibrillation (VF) was electrically induced and untreated for 30s. A sequence of randomized biphasic electrical shocks ranging from 10 to 100J was attempted. If the defibrillation failed to terminate VF, a 100J rescuer shock was then delivered. After a recovery interval of 5min, the sequence was repeated for a total of approximately 30 test shocks were attempted for each animal. The dose response curves were constructed and the defibrillation thresholds were compared between groups. ResultsThe aggregated success rate was 65.6% for AP placement and 43.0% for AL one (p=0.0005) when shock energy was between 10 and 70J. A significantly lower 50% defibrillation threshold was obtained for AP pads placement compared with traditional AL pads position (2.1±0.4J/kg vs. 3.6±0.9J/kg, p=0.041). ConclusionIn this pediatric porcine model of cardiac arrest, the anterior–posterior placement of pediatric pads yielded a higher success rate by lowering defibrillation threshold compared to the anterior–lateral position.

Radiation Exposure During Pediatric Videourodynamics

Videourodynamics is useful for evaluating and treating neurological disorders in children. Traditional urodynamic parameters can be obtained while simultaneous visualization of the urinary system can reveal anatomical anomalies. This additional information comes at the cost of radiation exposure to the child. We characterized radiation exposure from videourodynamics. We reviewed all recent videourodynamic studies and recorded patient demographics, urological diagnoses, physical attributes, total fluoroscopy time, total radiation exposure in mGy, bladder capacity and the number of filling cycles performed. Multivariate linear regression was used to identify patient factors that independently influenced total radiation exposure. A total of 64 videourodynamic studies were performed in 34 female and 28 male patients with a mean age of 8.6 years (95% CI 7.2-10.0). The most common diagnosis was neurogenic bladder in 40 patients, although 49 had multiple diagnoses. Mean total fluoroscopy time was 1.8 minutes (95% CI 1.4-2.1) and mean total radiation exposure was 10 mGy (95% CI 7.5-13.3). On multivariate linear regression patient weight and bladder capacity were the only independent predictors of total radiation exposure. Videourodynamics entail significant radiation exposure. Patient weight and bladder capacity were independent predictors of total radiation exposure. Physician awareness of radiation exposure may result in the judicious use of fluoroscopy and aid in counseling parents on the risk of videourodynamics. Further research is needed to quantify organ specific doses of radiation due to medical imaging in children and the associated cancer risks.

Intrathoracic Pressure Regulation Improves 24-Hour Survival in a Pediatric Porcine Model of Hemorrhagic Shock

Hemorrhagic shock is a common cause of mortality and morbidity in the pediatric population. Intrathoracic pressure regulation (IPR) lowers intrathoracic pressure, thereby decreasing intracranial pressure and increasing venous return, cardiac output, and cerebral perfusion without the need for immediate fluid resuscitation. We hypothesized that IPR would improve hemodynamics and 24-h survival in a pediatric porcine model of hemorrhagic shock. Twenty piglets were subjected to a 50% total blood volume hemorrhage over 15 min and then randomized to treatment with either IPR or no treatment. After 60 min, survivors were autotransfused, weaned from the ventilator, and assessed and autopsied at 24 h. Mean arterial pressures (MAPs), cardiac index (CI), and arterial blood gases were recorded. MAP (mm Hg) was significantly higher in the IPR group (60.8 ± 3.7) versus controls (41.2 ± 4.6, p < 0.01). Mean CI (L/min/m²) was significantly higher with IPR (3.9 ± 0.24) versus controls (2.5 ± 0.39, p < 0.01). IPR survival rates were significantly improved with IPR [9/9 (IPR) versus 5/11 (controls); p < 0.02]. In this piglet model of hemorrhagic shock, IPR treatment safely and significantly improved MAP, CI, and 24-h survival rates.

Effects of norepinephrine on dynamic variables of fluid responsiveness during hemorrhage and after resuscitation in a pediatric porcine model

The effect of vasopressors on pulse pressure variation (PPV), stroke volume variation (SVV) and on the volumetric variable global end-diastolic volume (GEDV) during changing loading conditions is currently under debate. The aim of our study was to investigate the effect of norepinephrine (NE) on PPV, SVV and GEDV in a pediatric animal model of hemorrhage and resuscitation. Eight anesthetized piglets were studied at normovolemia, after stepwise blood withdrawal (25 ml x kg(-1)), after infusion of NE to restore mean arterial pressure (MAP), after NE titration was stopped and shed blood was retransfused and finally again after NE titration. Stroke volume (SV) was measured using a thermodilution pulmonary artery catheter. GEDV was measured by transpulmonary thermodilution. PPV and SVV were monitored continuously by pulse contour analysis. In response to NE administration during hemorrhage, MAP significantly increased (P < 0.01), PPV significantly decreased (P = 0.02), whereas SVV, SV and GEDV remained unchanged. After retransfusion, SVV and GEDV significantly correlated with volume induced percentage change in SV. This significant correlation was reversed after NE administration for SVV and persisted for GEDV. In conclusion, NE administration significantly affected PPV and SVV, whereas the volumetric variable GEDV remained unchanged.

Abstract 2840: An Impedance Threshold Device Improves 24 Hour Survival in a Spontaneously Breathing Pediatric Porcine Model of Hemorrhagic Shock

Introduction: Traumatic injury and hypovolemic shock are leading causes of death in children worldwide. We previously demonstrated that augmentation of negative intrathoracic pressure generated by spontaneously breathing through an impedance threshold device (ITD) improves blood pressure and cardiac output in a pediatric porcine model of hemorrhagic shock. However, the optimal method to restore intravascular volume, prevent secondary organ damage, and prevent progression of reversible shock to irreversible circulatory collapse after severe blood loss in children is not known. Hypothesis: Breathing through an ITD for 90 min prior to fluid resuscitation will safely increase short and long-term survival rates. Methods: Seventeen spontaneously breathing female piglets (12.4 ± 0.1 kg), anesthetized with propofol, were subjected to a 40% bleed and randomized in a prospective, blinded manner to either a sham or active ITD (cracking pressure of -7 cmH2O, Advanced Circulatory Systems, Minneapolis, MN) for 90 min. Shed blood was then reinfused. Work of breathing (WOB), 90 minute and 24 hour survival were evaluated. Survival analysis was performed using the Wilcoxon Rank Sum Test, Fischer’s Exact Test, and Kaplan-Meier Methods. Results: Baseline and post-bleed heart rate, blood pressure, lactate levels, and arterial blood gas parameters were similar between groups. Piglets treated with the active ITD had significantly improved survival compared to the piglets treated with the sham ITD at 90 min (8/9 vs. 3/8, p=0.04). At 24 hours, Kaplan-Meier curve analysis revealed improved survival with the active ITD (6/9 vs. 2/8, p=0.04). The 3 animals in the active ITD group that did not survive died at a median time of 280 minutes (82–580), and the 6 animals in the sham group that did not survive, died at a median time of 69 minutes (24 –101) after bleed (p=0.11). The WOB at 45 min (J/L) was 73% higher in the active ITD group than the sham group (1.18 ± 0.07 vs. 0.68 ± 0.07, p= 0.001). The piglets safely tolerated the active ITD therapy. Conclusion: In this spontaneously breathing, anesthetized piglet model of hemorrhagic shock, treatment with an active ITD for 90 min without supplemental fluid resuscitation significantly improved short and long-term survival rates.

Mechanical ventilation with heliox decreases respiratory system resistance and facilitates CO2 removal in obstructive airway disease

Sir: Helium has a density that is one-seventh that of air, resulting in a decreased resistance to gas flow allowing for increased bulk and oxygen flow. Additionally, CO2 diffuses through helium much easier than through air [1, 2]. The beneficial effect of heliox on lowering the respiratory system resistance (Rrs) has been demonstrated in a pediatric porcine model of obstructive airway disease (OAD) [3]. However, the

Radiation Exposure Reduction during Voiding Cystourethrography in a Pediatric Porcine Model of Vesicoureteral Reflux

To compare grid-controlled variable-rate pulsed fluoroscopy (GCPFL) and continuous fluoroscopy (CFL) for the reduction of radiation exposure during voiding cystourethrography (VCUG) in a pediatric porcine model of vesicoureteral reflux. Institutional animal care and use committee approval was obtained. Vesicoureteral reflux was simulated in four pigs, and 48 VCUG studies were performed (24 with GCPFL, 24 with CFL). VCUG was performed at abdominal girths of 8-10 cm (group 1, simulates human newborn to 6-month-old infant), 12-13 cm (group 2, simulates 2-3-year-old child), and 15-17 cm (group 3, simulates 10-year-old child). An electronic device calculated total radiation exposure during fluoroscopy and image recording. With five-point ordinal scales, VCUG images were scored independently for anatomic conspicuity and overall diagnostic quality by two radiologists (radiologists A and B). An analysis of variance was used to compare radiation exposures and fluoroscopy times between GCPFL and CFL and to determine whether radiation exposure and fluoroscopy time were dependent on the pig's abdominal girth. The Pearson product-moment correlation coefficient was used to assess whether fluoroscopy time was correlated with radiation exposure. Anatomic conspicuity and diagnostic quality scores were compared by means of the Wilcoxon signed rank test. Results of analysis of variance revealed that GCPFL resulted in a significant reduction in total radiation exposure compared with CFL for each of the three groups (P < .05 for each comparison), and this reduction was most marked in the larger animals. There were no significant differences in diagnostic quality of the recorded VCUG images (P > .05). Anatomic conspicuity was not significantly different for groups 2 and 3, but there was a significantly higher score for GCPFL in group 1 for radiologist A (P = .04). By using GCPFL in the performance of VCUG in a pediatric porcine model of vesicoureteral reflux, total radiation exposure can be reduced by a factor of 4.6-7.5 lower than with CFL, and diagnostic-quality images can be obtained.

Spontaneous breathing through an inspiratory impedance threshold device augments cardiac index and stroke volume index in a pediatric porcine model of hemorrhagic hypovolemia

Hemorrhagic shock secondary to trauma is associated with poor survival. The impedance threshold device (ITD) has been shown to improve blood pressure and survival rates in an adult porcine model of hemorrhagic hypovolemia. Pediatric hemodynamics, anatomy, and physiology differ from adults. Evaluation of the ITD has not been previously assessed in a pediatric porcine model of hypovolemia induced by hemorrhage. To determine whether ITD-assisted breathing, with and without positive end-expiratory pressure, will improve key hemodynamic parameters following hypovolemia induced by hemorrhage in a pediatric porcine model. Intubated, anesthetized, hemodynamically stable, spontaneously breathing piglets were rapidly bled 40% of their calculated blood volume. Piglets' hemodynamic and intrathoracic pressures were continuously monitored during 10-min normovolemic baseline, bleed to hypotensive baseline, 10-min ITD-assisted breathing, 10 mins without ITD, 10-min ITD-assisted breathing randomized with or without positive end-expiratory pressure (3 cm H2O), 10 mins without ITD, reinfusion of shed blood, 10-min baseline following return to normovolemia. The ITD had an inspiratory cracking pressure of -7 cm H2O. Transthoracic echocardiographic parameters were measured at the end of each 10-min period. There was no significant difference in baseline assessments between groups. Systolic blood pressure, cardiac index, and stroke volume index were significantly greater during ITD-assisted breathing. There was a trend toward increased left ventricular end-diastolic dimension during ITD use. Heart rate, systemic vascular resistance index, left ventricular end-systolic dimension, and shortening fraction did not change significantly during ITD-assisted breathing. There was equivalent improvement in systolic blood pressure, cardiac index, and stroke volume index, when the ITD alone and ITD plus positive end-expiratory pressure were used. ITD-assisted breathing significantly augmented systolic blood pressure, cardiac index, and stroke volume index in this pediatric porcine model of hemorrhagic hypovolemia. These effects appear related to increased left ventricular preload and not by increased systemic vascular resistance or heart rate. These beneficial effects of ITD-assisted breathing are not changed by the addition of positive end-expiratory pressures of 3 cm H2O.

Heliox improves pulmonary mechanics in a pediatric porcine model of induced severe bronchospasm and independent lung mechanical ventilation.

BACKGROUND: A helium-oxygen gas mixture (heliox) has low gas density and low turbulence and resistance through narrowed airways. The effects of heliox on pulmonary mechanics following severe methacholine-induced bronchospasm were investigated and compared to those of a nitrogen-oxygen gas mixture (nitrox) in an innovative pediatric porcine, independent lung, mechanical ventilation model. RESULTS: All of the lungs showed evidence of severe bronchospasm after methacholine challenge. Prospective definition of 'heliox response' was a 15% or greater improvement in lung function in the lung receiving heliox compared with the matched lung receiving nitrox. Seven out of 10 pigs responded to heliox therapy with respect to resistance and eight out of 10 pigs responded to heliox therapy with respect to compliance and tidal volume (P < 0.03). After crossover from nitrox to heliox, eight out of eight lungs significantly improved with respect to tidal volume, resistance and compliance (P < 0.001). After crossover from heliox to nitrox all eight lungs showed a significant increase in resistance and a significant decrease in tidal volume (P < 0.001). CONCLUSIONS: In a pediatric porcine model of acute, severe methacholine-induced bronchospasm and independent lung mechanical ventilation, administration of heliox improves pulmonary mechanics, gas flow, and ventilation. Administration of heliox should be considered for support of pediatric patients with acute, severe bronchospasm requiring mechanical ventilation through small artificial airways.

Anesthetic regimen effects on a pediatric porcine model of asphyxial arrest

The effects of three anesthetic regimens on an established model of pediatric porcine hypoxic-hypercarbic arrest were examined. Twenty-four preadolescent miniature piglets were paralyzed, mechanically ventilated and anesthetized with one of three regimens: IM+IV pentobarbital ( n=8); IM+IV ketamine ( n=8); or IM ketamine+inhaled isoflurane ( n=8). Asphyxial cardiopulmonary arrest was induced and, after an 8 min cardiac arrest nonintervention interval, a standardized protocol of manual CPR with mechanical ventilation was performed. Outcome variables included incidence of ventricular fibrillation, time to cardiac arrest, endogenous plasma epinephrine levels and arteriovenous epinephrine gradients. IV Ketamine anesthesia produced the highest incidence of ventricular fibrillation ( P<0.01 vs. pentobarbital and isoflurane). Time to asphyxia induced cardiac arrest was greatest for the pentobarbital group ( P<0.05 vs. ketamine and isoflurane). During induction of asphyxial cardiac arrest (low cardiac flow), endogenous venous epinephrine accumulation was highest in the pentobarbital anesthetized group ( P<0.05). After 8 min of untreated cardiac arrest and 1 min of CPR (low flow), arterial epinephrine levels were highest in the ketamine group ( P<0.05). Endogenous epinephrine gradients were venous>arterial in all groups at the end of the 8 min cardiac arrest non-intervention interval (no flow). After 1 min of CPR, the gradients had either equalized or reversed to arterial>venous in all groups except for pentobarbital. As designed and expected, return of spontaneous circulation did not occur in any animal. We conclude that, in developing models of porcine asphyxial cardiopulmonary arrest and resuscitation to simulate pediatric human arrest, variations in anesthetic regimen produce significant differences in parameters that are important to consider: time to asphyxia induced cardiac arrest, fibrillation threshold, plasma epinephrine level and arteriovenous epinephrine gradient. Anesthetic effects need to be carefully considered and clearly explained to facilitate the interpretation of studies of interventions in cardiopulmonary arrest and resuscitation.