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Interleukin (IL)-11, a multifunctional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit α-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of nonatopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 attenuates lung inflammation and increases airway responsiveness after acute inhalation exposure to ozone (O3), a criteria pollutant and nonatopic asthma stimulus. Accordingly, 4 and/or 24 h after cessation of exposure to filtered room air or O3, we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O3-exposed IL-11Rα1-deficient as compared with O3-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O3-exposed mice. However, airway responsiveness to acetyl-β-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared with wild-type mice after O3exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of nonatopic asthma.

Pediatric acute respiratory distress syndrome (PARDS) incidence is reported between 2.95 to 12.8 cases per 100,000 person years,1,2 which is lower than in adults but remains one of the most challenging form of lung diseases for a Pediatric Intensivist. Application of the adult ARDS definition is limited in pediatrics due to differences in risk factors, etiology, pathophysiology, hard to obtain PaO2 values, and lower levels and variation of PEEP utilization. To address these limitations, to promote early recognition and diagnosis of PARDS, and to improve prognostication and stratification of disease severity, the Pediatric Acute Lung Injury Consensus Conference (PALICC) published the first definition for PARDS in 2015.3 This definition (Table 1) kept the criteria of onset within seven days of a known clinical insult and the presence of respiratory failure not fully explained by cardiac failure or fluid overload. It eliminated the term acute lung injury, excluded bilateral infiltrate, and stratified severity of PARDS based on the oxygenation deficit as mild, moderate, and severe. Either oxygenation index or the oxygen saturation index (when arterial blood gas is not available) can be used to assess the degree of hypoxemia. Non-invasive ventilation is now included for continuous positive airway pressure of more than 5 cm H2O. Furthermore, PALICC included recommendations for defining PARDS in children with preexisting chronic lung disease, cyanotic congenital heart disease, and left ventricular dysfunction. The PARDS management guidelines are based on very limited pediatric data and are largely based on expert opinions.3 For ventilatory management, no mode of ventilation is found to be superior, patient-specific tidal volumes per ideal body weight according to disease severity are recommended (3–6 mL/kg for patients with reduced and 5–8 mL/kg for patients with better-preserved compliance). In the absence of transpulmonary pressure measurements, plateau pressure should be limited to 28 cm H2O and 29–32 cm H2O during increased chest wall elastance. Moderately elevated PEEP to 10–15 cm H2O should be titrated in severe PARDS to the observed oxygenation and hemodynamic response. The oxygenation goal for mild PARDS (PEEP 10) 88–92%, although in some patients, 7.15 is the goal except in severe pulmonary hypertension, intracranial hypertension, select congenital heart lesions, significant ventricular dysfunction with hemodynamic instability, and pregnancy. Recruitment maneuvers by slow incremental and decremental PEEP steps may be used for severe hypoxemia. High-frequency oscillatory ventilation remains as an alternative ventilatory mode for patients with moderate-to-severe PARDS. There is not enough evidence to support the routine use of inhaled nitric oxide, steroids, or prone positioning for PARDS at this time.3 Since the publication of the new definition, several studies comparing the previous definitions to PALICC suggest that the PALICC definition can not only identify more patients with PARDS but it is also better at risk stratification for mortality.4,5 Despite decades of research and experience of managing PARDS, there remains a lack of definitive clinical evidence in Pediatrics. Further pediatric research is needed to gain more insight and to improve outcome of PARDS.

Pediatric intensivists are called to patient bedsides in the pediatric cardiac intensive care unit (CICU) after congenital cardiac surgery for low blood pressure (BP) and/or poor perfusion, acute change in heart rate (HR) or rhythm, surgical site bleeding or increased chest tube output, anuria or oliguria, oxygen desaturation less than expected or metabolic acidosis with rising lactic acid and base deficit. Causes of acute circulatory failure after cardiac surgery are divided into four categories which must be considered when approaching the patient in CICU (Table 1). Assessing cardiac output in CICU remains challenging, hemodynamic parameters are usually monitored, along with physical examination, i.e. HR, BP, right and left atrial pressures. There are surrogate markers i.e., mixed venous saturation, brain and renal NIRS, toe temperature, urine output, and then laboratory workup to determine acidosis due to end-organ dysfunction. Echocardiography can confirm low cardiac output syndrome (LCOS) occurs after cardiac surgery with the following major indicators; abnormal ventricular-vascular interaction after bypass, the functionally univentricular circulation, abnormal diastolic function after surgery to the right heart and residual anatomic lesions.1 The limited support tools that are available to manage circulatory failure post cardiac surgery in the CICU are the following: Medications: High labile pulmonary vascular tone (PVR) occurs in patients with pulmonary over-circulation i.e., ASD (atrial septal defect), VSD (ventricular septal defect), PDA (patent ductus arteriosus) and AV canal (atrioventricular canal). Pulmonary venous hypertension, i.e. TAPVR with obstruction, HLHS with restrictive atrial communication and in the univentricular heart after Norwood, shunt or PA band has unstable PVR. Functionally univentricular hearts don't tolerate increased SVR and at the same time, decreased SVR may not be desirable for patients who have fixed systemic or pulmonary obstruction. There are a wide variety of medications to use, but essentially two, milrinone2,3 and epinephrine are very important and widely used. Milrinone is routinely used after cardiac surgery to minimize the LCOS, which works in a receptor independent manner and is synergistic to beta-adrenergic ionotropic effect. Most patients benefit from low dose epinephrine for decreased cardiac function. Nitroprusside is effective where after-load is high, a low dose should always be started titrating to the optimal BP. Generally, there is no role of dopamine in these patients.4 Ventilation-cardiopulmonary interaction: Ventilation at functional residual capacity needs to be targeted. Managing rhythm: Recognition of rhythm is a crucial aspect of care. It is equally important to pay attention to the appropriate heart rate. Extracorporeal mechanical support: The last resort is to put the patient on extracorporeal membrane oxygenation. In summary, the past two decades have seen important advances in our understanding of the circulatory physiology of infants and children post cardiac surgery. When approaching the patients with cardiovascular dysfunction, it is essential to approach the cardiopulmonary system in its entirety, rather than consider the heart, lungs, or peripheral circulation as isolated elements. Working towards one common goal of optimizing systemic oxygen delivery and emphasizing anticipatory intensive care tailored to individual patients with the need for early, targeted investigation and intervention is essential when patients are not progressing as expected.

Inhalation of ozone (O3), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O3. Furthermore, each of these aforementioned cells express chemokine (C‐C motif) receptor‐like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O3‐induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O3, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O3. To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl‐β‐methylcholine chloride (respiratory system resistance) in wild‐type and mice genetically deficient in Ccrl2 (Ccrl2‐deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O3. In air‐exposed mice, BALF chemerin was greater in Ccrl2‐deficient as compared to wild‐type mice. O3 increased BALF chemerin in mice of both genotypes, yet following O3 exposure, BALF chemerin was greater in Ccrl2‐deficient as compared to wild‐type mice. O3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O3 exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O3‐induced lung pathology.

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin ( ob/ ob mice) or the long isoform of the leptin receptor ( db/ db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure ( Cpefatmice). Accordingly, Cpefatand lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpefatcompared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.

Objective To evaluate the hemodynamic effects of using an adhesive glove device (AGD) to perform active compression–decompression CPR (AGD-CPR) in conjunction with an impedance threshold device (ITD) in a pediatric cardiac arrest model. Design Controlled, randomized animal study. Methods In this study, 18 piglets were anesthetized, ventilated, and continuously monitored. After 3 min of untreated ventricular fibrillation, animals were randomized (6/group) to receive either standard CPR (S-CPR), active compression–decompression CPR via adhesive glove device (AGD-CPR) or AGD-CPR along with an ITD (AGD-CPR + ITD) for 2 min at 100–120 compressions/min. AGD is delivered using a fingerless leather glove with a Velcro patch on the palmer aspect and the counter Velcro patch adhered to the pig's chest. Data (mean ± SD) were analyzed using one-way ANOVA with pair wise multiple comparisons to assess differences between groups. p -Value ≤ 0.05 was considered significant. Results Both AGD-CPR and AGD-CPR + ITD groups produced lower intrathoracic pressure (IttP, mmHg) during decompression phase (−13.4 ± 6.7, p = 0.01 and −11.9 ± 6.5, p = 0.01, respectively) in comparison to S-CPR (−0.3 ± 4.2). Carotid blood flow (CBF, % of baseline mL/min) was higher in AGD-CPR and AGD-CPR + ITD (respectively 64.3 ± 47.3%, p = 0.03 and 67.5 ± 33.1%, p = 0.04) as compared with S-CPR (29.1 ± 12.5%). Coronary perfusion pressure (CPP, mmHg) was higher in AGD-CPR and AGD-CPR + ITD (respectively 19.7 ± 4.6, p = 0.04 and 25.6 ± 12.1, p = 0.02) when compared to S-CPR (9.6 ± 9.1). There was no statistically significant difference between AGD-CPR and AGD-CPR + ITD groups with reference to intra-thoracic pressure, carotid blood flow and coronary perfusion pressure. Conclusion Active compression decompression delivered by this simple and inexpensive adhesive glove device resulted in improved cerebral blood flow and coronary perfusion pressure. There was no statistically significant added effect of ITD use along with AGD-CPR on the decompression of the chest.

Objective ACD-CPR improves coronary and cerebral perfusion. We developed an adhesive glove device (AGD) and hypothesized that ACD-CPR using an AGD provides better chest decompression resulting in improved carotid blood flow as compared to standard (S)-CPR. Design Prospective, randomized and controlled animal study. Methods Sixteen anesthetized and ventilated piglets were randomized after 3min of untreated VF to receive either S-CPR or AGD-ACD-CPR by a PALS certified single rescuer with compressions of 100min −1 and C:V ratio of 30:2. AGD consisted of a modified leather glove exposing the fingers and thumb. A wide Velcro patch was sewn to the palmer aspect of the glove and the counter Velcro patch was adhered to the pig's chest wall. Carotid blood flow was measured using ultrasound. Data (mean±SD) was analyzed using one way ANOVA and unpaired t -test; p -value≤0.05 was considered statistically significant. Results Right atrial pressure (mmHg) during the decompression phase was lower during AGD-ACD-CPR (−3.32±2.0) when compared to S-CPR (0.86±1.8, p =0.0007). Mean carotid blood flow was 53.2±27.1 (% of baseline blood flow in ml/min) in AGD vs. 19.1±12.5% in S-CPR, p =0.006. Coronary perfusion pressure (CPP, mmHg) was 29.9±5.8 in AGD vs. 22.7±6.9 in S-CPR, p =0.04. There was no significant difference in time to ROSC and number of epinephrine doses. Conclusion Active chest decompression during CPR using this simple and inexpensive adhesive glove device resulted in significantly better carotid blood flow during the first 2min of CPR.

We developed an adhesive glove device (AGD) to perform ACD-CPR in pediatric manikins, hypothesizing that AGD-ACD-CPR provides better chest decompression compared to standard (S)-CPR.Split-plot design randomizing 16 subjects to test four manikin-technique models in a crossover fashion to AGD-ACD-CPR vs. S-CPR. Healthcare providers performed 5min of CPR with 30:2 compression:ventilation ratio in the four manikin models: (1) adolescent; (2) child two-hand; (3) child one-hand; and (4) infant two-thumb.Modified manikins recorded compression pressure (CP), compression depth (CD) and decompression depth (DD). The AGD consisted of a modified oven mitt with an adjustable strap; a Velcro patch was sewn to the palmer aspect. The counter Velcro patch was bonded to the anterior chest wall. For infant CPR, the thumbs of two oven mitts were stitched together with Velcro. Subjects were asked to actively pull up during decompression. Subjects' heart rate (HR), respiratory rate (RR) and recovery time (RT) for HR/RR to return to baseline were recorded. Subjects were blinded to data recordings. Data (mean+/-SEM) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as Por =0.05.Mean decompression depth difference was significantly greater with AGD-ACD-CPR compared to S-CPR; 38-75% of subjects achieved chest decompression to or beyond baseline. AGD-ACD-CPR provided 6-12% fewer chest compressions/minute than S-CPR group. There was no significant difference in CD, CP, HR, RR and RT within each group comparing both techniques.A simple, inexpensive glove device for ACD-CPR improved chest decompression with emphasis on active pull in manikins without excessive rescuer fatigue. The clinical implication of fewer compressions/minute in the AGD group needs to be evaluated.

This article summarizes the current state of outcomes and outcome predictors following pediatric cardiopulmonary arrest with special emphasis on neurologic outcome. The authors briefly describe the factors associated with outcome and review clinical signs, electrophysiology, neuroimaging, and biomarkers used to predict outcome after cardiopulmonary arrest. Although clinical signs, imaging, and somatosensory evoked potentials are best associated with outcome, there are limited data to guide clinicians. Combinations of these predictors will most likely improve outcome prediction, but large-scale outcome studies are needed to better define these predictors.

Objective: Systolic blood pressure (SBP) and mean arterial pressure (MAP) are essential evaluation elements in ill children, but there is wide variation among different sources defining systolic hypotension in children, and there are no normal reference values for MAP. Our goal was to calculate the 5th percentile SBP and MAP values in children from recently updated data published by the task force working group of the National High Blood Pressure Education Program and compare these values with the lowest limit of acceptable SBP and MAP defined by different sources. Design: Mathematical analysis of clinical database. Methods: The 50th and 95th percentile SBP values from task force data were used to derive the 5th percentile value for children from 1 to 17 yrs of age stratified by height percentiles. MAP values were calculated using a standard mathematical formula. Calculated SBP values were compared with systolic hypotension definitions from other sources. Linear regression analysis was applied to create simple formulas to estimate 5th percentile SBP and 5th and 50th percentile MAP for different age groups at the 50th height percentile. Results: A 9‐21% range in both SBP and MAP values was noted for different height percentiles in the same age groups. The 5th percentile SBP values used to define hypotension by different sources are higher than our calculated values in children but are lower than our calculated values in adolescents. Clinical formulas for calculation of SBP and MAP (mm Hg) in normal children are as follows: SBP (5th percentile at 50th height percentile) 2 age in years 65, MAP (5th percentile at 50th height percentile) 1.5 age in years 40, and MAP (50th percentile at 50th height percentile) 1.5 age in years 55. Conclusion: We developed new estimates for values of 5th percentile SBP and created a table of normal MAP values for reference. SBP is significantly affected by height, which has not been considered previously. Although the estimated lower limits of SBP are lower than currently used to define hypotension, these values are derived from normal healthy children and are likely not appropriate for critically ill children. Our data suggest that the current values for hypotension are not evidence-based and may need to be adjusted for patient height and, most important, for clinical condition. Specifically, we suggest that the definition of hypotension derived from normal children should not be used to define the SBP goal; a higher target SBP is likely appropriate in many critically ill and injured children. Further studies are needed to evaluate the appropriate threshold values of SBP for determining hypotension. (Pediatr Crit Care Med 2007; 8:138‐144)

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines—including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)—promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

Objective. Compare airway pressure measurements at the ventilator Y-piece of the breathing circuit (P Y ) to intratracheal pressure measured at the distal end (P T ) of the endotracheal tube (ETT) during mechanical ventilation and spontaneous breathing of intubated children. Methods. Thirty children (age range 29 days to 5 years) receiving general anesthesia were intubated with an ETT incorporating a lumen embedded in its sidewall that opened at the distal end to measure P T . Peak inflation pressure (PIP) was measured at P Y and P T during positive pressure ventilation. Just before extubation, all measurements were repeated and imposed resistive work of breathing (WOBi) was calculated at both sites while breathing spontaneously. Results. Average PIP was approximately 25% greater at P Y (19.7 ± 3.4 cm H2O) vs. P T (15.0 ± 2.9 cm H2O), p < 0.01. During spontaneous inhalation P T was 59% lower ({bond}8.5 ± 4.0 cm H2O) vs. P Y ({bond}3.5 ± 2.0 cm H2O), p < 0.01. WOBi measured at P Y (0.10 ± 0.02 Joule/L) was 86% less than WOBi measured at P T (0.70 ± 0.40 Joule/L), p < 0.01. Conclusions. In healthy children P Y significantly overestimates PIP in the trachea during positive pressure ventilation and underestimates the intratracheal airway pressure during spontaneous inhalation. During positive pressure ventilation P T better assesses the pressure generated in the airways and lungs compared to P Y because P T also includes the difference in airway pressure across the ETT tube due to resistance. During spontaneous inhalation, P T reflects the series resistance of the ETT and ventilator circuit, while P Y reflects only the resistance of the ventilator circuit, accounting for the smaller decreases in pressure. Additionally, P Y underestimates the total WOBi load on the respiratory muscles. Thus, P T is a more accurate reflection of pulmonary airway pressures than P Y and suggests that it should be incorporated into ventilator systems to more accurately trigger the ventilator and to reduce work of breathing.

OBJECTIVE Therapeutic hypothermia improves neurologic outcome and survival after adult out-of-hospital cardiac arrest. To help us design a prospective hypothermia trial in children, we developed a survey to assess current knowledge and attitude of pediatric critical care providers regarding therapeutic hypothermia and potential impediments to implementing a prospective study. DESIGN Anonymous survey. SETTING Internet-based survey of pediatric critical care community. INTERVENTIONS None. RESULTS A total of 159 responders completed the survey. Most respondents (92%) were fellowship-trained in pediatric critical care, with 9.9 +/- 6.5 yrs of experience. Many (85%) worked in the United States; 89% were in large tertiary care centers with residency or fellowship training programs. Most (65%) were aware of the adult randomized trials of therapeutic hypothermia, but only 9% (always) or 38% (sometimes) utilize this therapy. The most common reason to use hypothermia was likelihood of patient recovery, absence of life-limiting disease, and presence of coma for >/=1 hr after resuscitation. The majority of responders using therapeutic hypothermia cool their patients to 33-35 degrees C for a duration ranging from as short as 12 hrs to as long as 96 hrs; 91% do not actively rewarm the patient. A majority (81%) agree that a randomized, controlled trial of therapeutic hypothermia in children is ethical, and 95% would be willing to randomize their patients. Finally, 81% thought that therapeutic hypothermia should be studied in other ischemic insults and not just cardiac arrest. CONCLUSIONS Despite widespread awareness of therapeutic hypothermia's beneficial effects after arrest, it is not widely used by pediatric critical care clinicians sampled in our survey. Among those using hypothermia, there is wide variation in methodology and end points of therapy. This seems to result from a lack of evidence, difficulty with the technique, and unavailability of explicit protocols. Pediatric studies are needed to assess the safety, feasibility, and effectiveness of therapeutic hypothermia after cardiac arrest and other causes of brain injury.

The in vivo mechanisms by which glucocorticoids inhibit nitric oxide expression await detailed investigation. In cell culture experiments, glucocorticoids have been shown to inhibit inducible nitric oxide synthase (iNOS) formation and activity. Glucocorticoids can inhibit iNOS activity in cultured cells by blocking arginine transport and inhibiting tetrahydrobiopterin biosynthesis. We recently reported that changes in intrapulmonary formation of nitric oxide in endotoxemic rats correspond with changes in transcription of the predominant arginine transporter cationic amino acid transporter (CAT)-2. Realizing that hemorrhagic shock induces nitric oxide overproduction in intact animals, we sought to explore whether glucocorticoids attenuate hemorrhagic shock-induced increases in intrapulmonary nitric oxide formation and whether they might do so by inhibiting the formation of tetrahydrobiopterin, iNOS protein, and CAT-2. We randomly assigned 10 male Sprague-Dawley rats to receive dexamethasone or normal saline. Bleeding the animals to a mean systemic blood pressure of between 40 and 45 mmHg created the hemorrhagic shock. Dexamethasone abrogated the increase in exhaled nitric oxide concentrations caused by hemorrhagic shock. At the end of the experiment, plasma nitrate/nitrite values were lower in the dexamethasone group than in the control group. The iNOS protein concentrations were also lower in the dexamethasone group than in the control group. Dexamethasone decreased the intrapulmonary iNOS mRNA concentrations yet increased both guanosine triphosphate cyclohydrolase I mRNA and CAT-2 mRNA. Our results support the idea that dexamethasone inhibits nitric oxide formation in a manner that is independent of tetrahydrobiopterin and arginine transport yet dependent on downregulation of iNOS mRNA expression.

Expression of plasminogen activator inhibitor (PAI)‐1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI‐1 regulates expression of interleukin (IL)‐6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)‐2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3. Given these observations, we hypothesized that PAI‐1 contributes to the severity of the aforementioned sequelae by regulating expression of IL‐6, KC, and MIP‐2 following acute exposure to O3. To test our hypothesis, wild‐type mice and mice genetically deficient in PAI‐1 (PAI‐1‐deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty‐four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL‐6, KC, MIP‐2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl‐β‐methylcholine chloride (respiratory system resistance) were measured in wild‐type and PAI‐1‐deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild‐type and PAI‐1‐deficient mice. With the exception of MIP‐2, which was significantly lower in PAI‐1‐deficient as compared to wild‐type mice 24 h following cessation of exposure to O3, no other genotype‐related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI‐1 neither regulates pulmonary expression of IL‐6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

Infant CPR guidelines recommend two-finger chest compression with a lone rescuer and two-thumb with two rescuers. Two-thumb provides better chest compression but is perceived to be associated with increased ventilation hands-off time. We hypothesized that lone rescuer two-thumb CPR is associated with increased ventilation cycle time, decreased ventilation quality and fewer chest compressions compared to two-finger CPR in an infant manikin model.Crossover observational study randomizing 34 healthcare providers to perform 2 min CPR at a compression rate of 100 min(-1) using a 30:2 compression:ventilation ratio comparing two-thumb vs. two-finger techniques.A Laerdal Baby ALS Trainer manikin was modified to digitally record compression rate, compression depth and compression pressure and ventilation cycle time (two mouth-to-mouth breaths). Manikin chest rise with breaths was video recorded and later reviewed by two blinded CPR instructors for percent effective breaths. Data (mean+/-SD) were analyzed using a two-tailed paired t-test. Significance was defined qualitatively as por =0.05.Mean % effective breaths were 90+/-18.6% in two-thumb and 88.9+/-21.1% in two-finger, p=0.65. Mean time (s) to deliver two mouth-to-mouth breaths was 7.6+/-1.6 in two-thumb and 7.0+/-1.5 in two-finger, p0.0001. Mean delivered compressions per minute were 87+/-11 in two-thumb and 92+/-12 in two-finger, p=0.0005. Two-thumb resulted in significantly higher compression depth and compression pressure compared to the two-finger technique.Healthcare providers required 0.6s longer time to deliver two breaths during two-thumb lone rescuer infant CPR, but there was no significant difference in percent effective breaths delivered between the two techniques. Two-thumb CPR had 4 fewer delivered compressions per minute, which may be offset by far more effective compression depth and compression pressure compared to two-finger technique.

Introduction: In animals Active Compression-Decompression(ACD)-CPR improves hemodynamics compared with standard CPR (S-CPR). We evaluated the feasibility of achieving ACD-CPR with a novel, simple and inexpensive Adhesive Glove Device (AGD) in an infant manikin model using two thumb (TT) chest compression. Hypothesis: AGD-ACD CPR provides better chest decompression compared to S-CPR in an infant manikin model without excessive rescuer fatigue. Methods: Laerdal ™ Baby ALS Trainer manikin was modified to digitally record compression pressure (CP), compression depth (CD) and decompression depth (DD). The thumb portion of two oven mitts were sewn together and a Velcro adhesive patch was stitched on the underside with an encircling adjustable strap for proper fit to create the AGD. An interlocking Velcro patch was glued to the manikin chest wall. Sixteen BLS or PALS certified healthcare providers were prospectively randomized to perform either two-thumb S-CPR or AGD-ACD-CPR for 5 minutes with a 30:2 compression:ventilation ratio using a crossover design. During AGD-ACD-CPR subjects were asked to pull up during chest decompression. Rescuer heart rate (HR), respiratory rate (RR), recovery time (RT) for HR/RR to return to baseline and actual compressions delivered per minute were recorded. Subjects were blinded to data recordings. Data (mean±SEM) was analyzed using 2 sided paired t-test; p-value ≤0.05 was considered significant. Results: Chest decompression was greater with AGD-ACD-CPR; the mean DD difference was 0.11±0.02 inches, p= Conclusions: Active decompression and improved recoil was achievable with the use of our simple, inexpensive AGD in this infant CPR model. Use of our device did not result in excessive rescuer fatigue compared to S-CPR. The clinical significance of 6 less compressions/minute in the AGD-CPR group needs to be determined.

Summary Objective The effects of the recommended 30:2 compression:ventilation (C:V) ratio on chest compression rate (CR), compression depth (CD), compression pressure (CP) and rescuer fatigue is unknown during pediatric CPR. We hypothesized that a 30:2 C:V ratio will decrease compression depth and compression pressure and increase rescuer fatigue compared with a 15:2 ratio. Design Randomized crossover observational study. Methods Adolescent, child and infant manikins were modified to digitally record compression rate, compression depth, compression pressure and total compression cycles (CC). BLS or PALS certified volunteers were randomized to five CPR groups: adolescent (AD), child 1-hand (OH), child 2-hand (TH), infant two-finger (TF) and infant two-thumb (TT). Each rescuer performed each ratio for 5min with the order randomized. Rescuer heart rate (HR) and respiratory rate (RR) were recorded continuously during CPR and used to determine the recovery time (RT) for HR/RR to return to baseline. Data (mean±S.D.) were contrasted by paired differences for quantitative data and the sign rank test for ordinal data. Results Eighty subjects (16 per group) were randomized. The peak compression pressure and compression rate were not different within any group, but total compression cycle were higher in all 30:2 groups. Compression depth (mm) was not significantly different within any group. The rescuer's HR (bpm) increased significantly during 30:2 CPR in AD and OH group with no significant differences in RR and recovery time. Subjects reported that 15:2 CPR was easier to perform ( P Conclusion During single rescuer pediatric BLS, more compression cycles were achieved with 30:2 C:V ratio without effect on compression depth, pressure and rate. Increased HR with 30:2 C:V ratio was noted during larger manikin CPR without subjective difference of reported fatigue. Most rescuers in AD and TF group did not achieve recommended compression depth regardless of C:V ratio.

OBJECTIVE: To test the hypothesis that intravascular acid infusion promotes intrapulmonary nitric oxide formation by promoting inducible nitric oxide synthase (iNOS) and inhibiting endothelial nitric oxide synthase (eNOS) expression in rats. DESIGN: Prospective, placebo controlled, randomized laboratory study. SETTING: University laboratory. SUBJECTS: Twelve male Sprague-Dawley rats weighing 317 +/- 30 g served as study subjects. All animals were anesthetized, paralyzed, and mechanically ventilated throughout the experiment. INTERVENTIONS: The animals were randomized to receive either 0.1 N hydrochloric acid or 0.9% saline intravenously. The infusions were initially given at a rate of 11 mL/kg/hr for 15 mins and then at a rate of 0.95 mL/kg/hr for the remainder of the experiment. Exhaled nitric oxide concentrations and hemodynamic measurements were monitored throughout the experiment. Lung tissues were harvested for Western blot analysis and immunostaining 4 hrs after starting the intravascular infusion. MEASUREMENT AND MAIN RESULTS: At the end of the experiment, we found more than a four-fold higher concentration of exhaled nitric oxide in the acid-treated animals than in the saline-treated animals (p

This study was designed to determine how pH affects nitric oxide (NO) formation induced by lipopolysaccharide (LPS) in cultured murine macrophages (RAW 264.7). The initial pH of LPS-containing culture media was adjusted to one of eight values (6.8, 7.0, 7.2, 7.4, 7.6, 7.8, 8.0, and 8.2). After exposure to LPS for eighteen hours, the cultures were harvested for analysis of mRNA, protein, and nitrate/nitrite (stable by-products of NO). Analyses for these substances were performed using semiquantitative RT-PCR, immunoblotting, and colorimetric Griess assays, respectively. We found that acidic culture media favored expression of inducible nitric oxide synthase (iNOS) mRNA. However, alkaline media favored expression of iNOS protein. Our findings suggest that post-transcriptional mechanisms predominate over transcriptional ones in order to regulate pH-mediated effects on NO formation by murine macrophages. The optimal pH for NO formation by iNOS was found in our study to be around 7.2.