l-Malic Acid Facilitates Stem Cell-Driven Intestinal Epithelial Renewal through the Amplification of ß-Catenin Signaling by Targeting Frizzled7 in Chicks.

l-Malic acid (l-MA) contributes to energy metabolism and nutrient digestion, which is an alternative to antibiotics for livestock; however, it is not clear whether l-MA can replace antibiotics to promote intestinal development in chicks. To investigate the effects of l-MA on intestinal stem cells (ISCs) driving epithelial renewal, we employed in vivo chick feeding experiments, chick intestinal organoid (IO) models, and in vitro chick intestinal epithelial cell models. The results showed that the feed conversion rate and diarrhea scores were decreased with improved jejunal morphology and barrier function in the 0.5% l-MA group. l-MA promoted the proliferation and differentiation of ISCs, inhibited the cell apoptosis, increased the IO formation efficiency, surface area, budding efficiency, and number of buds, suggesting that l-MA promoted the expansion of ISCs. Furthermore, l-MA treatment dramatically upregulated the Wnt/ß-catenin signaling pathway in the jejunum. Importantly, Wnt transmembrane receptor Frizzled7 (FZD7) mRNA abundance was increased in response to dietary 0.5% l-MA. In addition, molecular docking analysis using Autodock software and isothermal titration calorimetry revealed that l-MA binds to Lys91 of FZD7 with high affinity, indicating a spontaneous interaction. The chick intestinal epithelial cells treated with 10 µM l-MA significantly increased cell viability, and the Wnt/ß-catenin signaling pathway was activated, but l-MA failed to upregulate the Wnt/ß-catenin signaling when treated with the FZD7-specific inhibitor Fz7-21 in chick intestinal epithelial cells, indicating that FZD7 is indispensable for l-MA activation of the Wnt/ß-catenin signaling. Collectively, l-MA stimulated ß-catenin signaling by targeting transmembrane receptor FZD7, which promoted ISC expansion and inhibited cell apoptosis to accelerate intestinal epithelial renewal in chicks.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Alterations of complex IV in the tissues of a septic mouse model.

OBJECTIVES: To characterize the mitochondrial respiratory chain complex IV(complex IV) activity and protein expression during polymicrobial sepsis. MATERIAL AND METHODS: Polymicrobial peritonitis, a clinically relevant mouse model of sepsis, was generated by cecum ligation and puncture (CLP) in Sprague- Dawley rats. The rats were randomly divided into 3 groups as follows: the sepsis without resuscitation (S), sepsis and fluid resuscitated (R) group, and a control (C) group. Twelve hours after the sepsis model was established, tissue specimens were obtained from the myocardium, liver and skeletal muscle. Mitochondrial respiratory chain complex IV activity of all tissue specimens was detected by spectrophotometry. Western blot was used to measure the liver mitochondrial respiratory chain complex IV protein content. The ultrastructure changes of mitochondria were detected by transmission electron microscopy. RESULTS: In myocardial cells, complex IV activity decreased significantly in the S and R groups as compared to the C group. There were no differences in complex IV activity between groups in skeletal muscle cells while in liver cells, complex IV activity and content was significantly decreased for the S group but no differences were observed between the C and R groups. Increased matrix volume and reduced density with generalized disruption of the normal cristae pattern was most extensive in the liver, followed by cardiac muscle cells with that in skeletal muscle cells been relatively mild in the S group. Mitochondrial fusion/fission and mitochondrial autophagy was also observed in the S group by transmission electron microscopy. Mitochondrial ultrastructure was preserved in the R-group and was similar to that seen in the C-group. CONCLUSIONS: Changes in complex IV activity and mitochondrial ultrastructure, a manifestation of the mitochondrial dysfunction varied depending on cell type. These changes are partly reversed by fluid therapy. Therapies aimed at mitochondrial resuscitation should be explored.

[Application of extracorporeal membrane oxygenation in children with acute respiratory distress syndrome].

The children with acute respiratory distress syndrome (ARDS) usually require ventilatory support treatment. At present, lung protective ventilation strategy is recommended for the treatment of ARDS. Extracorporeal membrane oxygenation (ECMO) can improve oxygenation and remove carbon dioxide by extracorporeal circuit, and can partially or completely take over cardiopulmonary function. ECMO support showed many advantages in treating severe ARDS, such as reducing ventilator-induced lung injury and correcting hypoxemia. Over the past few years, there has been an increase in the use of ECMO for ARDS in children. This paper reviews the applications of ECMO for the treatment of ARDS in children.

Suppression of plasminogen activator inhibitor-1 by inhaled nitric oxide attenuates the adverse effects of hyperoxia in a rat model of acute lung injury.

INTRODUCTION: Locally increased expression of plasminogen activator inhibitor-1 (PAI-1) in acute lung injury (ALI) is largely responsible for fibrin deposition in the alveolae and lung microvasculature. In vitro, nitric oxide (NO) effectively suppresses the ischemic induction of PAI-1. We aimed to investigate the effects of inhaled NO on PAI-1 expression in ALI in a rat model with and without hyperoxia. MATERIALS AND METHODS: Healthy adult rats were primed with lipopolysaccharide (LPS) via an intraperitoneal challenge followed by a second dose of LPS given intratracheally to induce ALI (LPS group), whereas the control groups were given sterile saline. All groups were allocated to subgroups according to gas exposure: NO (20 parts per million, NO), 95% oxygen (O), both (ONO), or room air (A). At 4h, 24h, 48h (after 4h or 24h exposure to the various gases, 24h gas intervention and then observation until 48h), the rat lungs were processed and PAI-1 protein and mRNA expression, histopathological lung injury scores and fibrin deposition were evaluated. RESULTS: At 4 and 24h, inhaled NO caused the PAI-1 mRNA levels in the LPS-NO and LPS-ONO subgroups to decrease compared with the untreated LPS subgroups. At 48h, higher PAI-1 mRNA levels than those of the corresponding control subgroup were only observed in the LPS-O subgroup, and these values were lower in the LPS-ONO subgroup than in the LPS-O subgroup. The trends of the PAI-1 protein levels mirrored those of PAI-1 mRNA. At 48h, PAI-1 protein levels in the LPS-NO and LPS-ONO subgroups were decreased compared with those in the untreated LPS subgroups. The histopathological lung injury scores and fibrin deposition in LPS subgroups that inhaled NO showed a decreasing trend compared with the untreated LPS subgroups. CONCLUSIONS: Inhaled NO can suppress elevated PAI-1 expression in rats with ALI induced by endotoxin. Although exposure to high-concentration oxygen prolongs the duration of PAI-1 mRNA overexpression in ALI, inhaled NO can reduce this effect and alleviate both fibrin deposition and lung injury.

The passive leg raise test to predict fluid responsiveness in children--preliminary observations.

OBJECTIVE: To assess whether the passive leg raising (PLR) test can predict fluid responsiveness in pediatric patients. METHODS: This was a prospective observational study in a tertiary care pediatric center. Hemodynamic parameters including heart rate, stroke volume and cardiac output were assessed at baseline, after passive leg raising (PLR), at second baseline, and after volume loading (10 mL/kg normal saline in 10 min). Cutoff values of 7.5 and 10 % increase in cardiac index (CI) with passive leg raising were explored as predictors of volume loading response. RESULTS: Overall, the changes in CI with passive leg raising varied widely and was a poor predictor of response to volume loading in children under 5 years of age. Of 40 patients, 23 had greater than 10 % increase in CI with PLR which predicted fluid responsiveness with a sensitivity of 94 % (95 % confidence interval 71,100) and specificity of 26 % (95 % confidence interval 10,48). Sensitivity was higher (100 % vs. 91 %) and specificity similar (27 % vs. 25 %) in predicting CI for those over 5 as compared to under 5 y, respectively. In patients over 5 y, simple linear regression revealed a positive correlation (R(2) = 21) while R(2) values were much lower (0-0.07) for those under 5 y. CONCLUSIONS: Cardiac index changes after PLR varies widely in children and may be a poor predictor to volume loading in children under 5-y-old. However, in those over 5 y, PLR may be helpful in predicting fluid responsiveness in pediatric patients.

[Changes of the hemodynamics and extravascular lung water after different-volume fluid resuscitation in a piglet model of endotoxic shock].

OBJECTIVE: Practice recommendations have evolved, and consensus now exists among leading organizations such as the American College of Critical Care Medicine (ACCM) and Surviving Sepsis Campaign that fluid infusion is best initiated with boluses of 20 ml/kg, commonly requires 40-60 ml/kg but can be as much as 200 ml/kg if the liver is not enlarged and/or rales are not heard. The present study aimed to investigate and compare the changes of the hemodynamics and extravascular lung water after higher volume fluid resuscitation in a piglet model of endotoxic shock. METHOD: Twenty piglets were used for establishing animal models of endotoxic shock by intravenous infusing lipopolysaccharide (LPS). The experimental animals were divided into three groups according to the volume infused during the resuscitation. The three groups received different volume of saline in less than an hour after endotoxic shock. By the PiCCO plus system, we investigated the changes of hemodynamics and extravascular lung water. RESULT: After fluid resuscitation, global end diastolic volume inder, (GEDI) and intrathoracic blood volume index, (ITBI) markedly increased in the group of 80 ml/kg and 120 ml/kg, but there was no change in the group of 40 ml/kg. GEDI: Fifteen min after fluid resuscitation R1 was (261 ± 64) ml/m(2), R2 (457 ± 124) ml/m(2), R3 (413 ± 148) ml/m(2), 4 h R1 (251 ± 68) ml/m(2), R2 (422 ± 70) ml/m(2), R3 (470 ± 160) ml/m(2); ITBI: Fifteen min after fluid resuscitation R1 was (335 ± 69) ml/m(2), R2 (550 ± 179) ml/m(2), R3 (520 ± 183) ml/m(2), 4 h R1 (314 ± 84) ml/m(2), R2 (534 ± 96) ml/m(2), R3 (594 ± 200) ml/m(2) (R1 vs. R2 vs. R3, F = 26.373, P < 0.05; R1 vs. R2, R1 vs. R3, P < 0.05; R2 vs. R3, P > 0.05). CI of all three groups significantly decreased when the models were established. After fluid resuscitation, the base level was maintained in the group of 80 ml/kg and 120 ml/kg, but it was under the basic level in the group of 40 ml/kg.Fifteen min after fluid resuscitation R1 was (4.5 ± 0.7) L/(min·m(2)), R2 (6.4 ± 2.2) L/(min·m(2)), R3 (5.5 ± 0.7) L/(min·m(2)), 4 h R1 (4.1 ± 1.0) L/(min·m(2)), R2 (5.2 ± 0.9) L/(min·m(2)), R3 (5.1 ± 0.8) L/(min·m(2)). There was no significant difference in CI between these two groups (P > 0.05).ELWI of the group of 80 ml/kg and 120 ml/kg were still higher than that of the group of 40 ml/kg, 15 min after fluid resuscitation R1 was (19.2 ± 8.6) ml/kg, R2 (29.2 ± 5.5) ml/kg, R3 (23.4 ± 8.2) ml/kg, 4 h R1 (18.3 ± 6.5) ml/kg, R2 (23.8 ± 2.6) ml/kg, R3 (21.4 ± 3.9) ml/kg, but there was no significant difference in ELWI among the groups (P > 0.05). CONCLUSION: Resuscitation with higher volume of fluid infusion in the early stage of endotoxic shock was more efficient to increase the preload and maintain the cardiac output at the baseline level, and might reduce the need for vasoactive agents. Meanwhile, resuscitation with higher volume of fluid in the early stage of endotoxic shock did not sharply increase the extravascular lung water.

[Effects of high volume hemofiltration on hemodynamics and oxygen metabolism at early stage of septic shock in piglet models].

OBJECTIVE: To observe the effects of hemofiltration at early stage of septic shock with different ultrafiltration doses, including hemodynamics, oxygen metabolism, inflammatory mediator in piglet models, and to evaluate the therapeutic effects of HVHF. METHOD: The 18 healthy young piglets (Shanghai species) were divided randomly into three groups:control group (n = 6), conventional volume hemofiltration (CVVH) group [n = 6, ultrafiltration volume = 30 ml/(kg·h)] and high volume hemofiltration (HVHF) group [n = 6, ultrafiltration volume = 50 ml/(kg·h)], the animal model of septic shock was established by injection of lipopolysaccharide (LPS) (150 µg/kg) O111: B4. During the experiment, the following observations were carried out for all groups:1) Changes of hemodynamics [heart rate (HR), mean arterial pressure (MABP), cardiac output (CO), systemic vascular resistance index (SVRI), intrathoracic blood volume (ITBV)] and oxygen metabolism [oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction rate (O2ER) ] at the time of B0h, 0 h, 2 h, 4 h and 6 h.2) changes of TNF-α, IL-6, IL-10 in plasma at different time points (B0h, 0 h, 2 h, 4 h, 6 h). RESULT: Significant difference in circulatory parameters, inflammatory mediators in plasma were found at B0h and 0 h among three groups; the CO in two treatment groups were higher than that in control group at 4 h, 6 h after model establishment (P < 0.05), and SVRI in HVHF groups were higher than that in other two groups at 4 h, 6 h after model was established (P < 0.05). The MABP in HVHF group [4 h (82 ± 17) mm Hg, 6 h (80 ± 12) mm Hg](1 mm Hg = 0.133 kPa) were higher than that in CVVH group at 4 h [(67 ± 12) mm Hg], 6 h [(69 ± 14) mm Hg] after model was established (P < 0.05). The levels of IL-6, IL-10, TNF-α in two treatment groups were lower than that in control group at 4 h and 6 h after model was established (P < 0.05), and the IL-6 [(281 ± 51) pg/ml], TNF-α [(67 ± 13) pg/ml] level in HVHF group was lower than that in CVVH group [IL-6(281 ± 51) pg/ml, TNF-α (67 ± 13) pg/ml] at 6 h (P < 0.05). The DO2 and VO2 in two treatment groups were higher than that in control group at 4 h, 6 h (P < 0.05), the O2ER in HVHF group were higher than that in CVVH group at 4 h (44% ± 3% vs. 33% ± 4%), 6 h (43% ± 5% vs. 31% ± 3%, P < 0.05). CONCLUSION: High volume hemofiltration (HVHF) at early stage of septic shock piglet models was more effective in improving hemodynamics, oxygen metabolism than conventional CVVH. And HVHF eliminated blood inflammatory mediators more effectively than conventional CVVH.

Effect of continuous blood purification on concentrations of plasma vasoactive substances and cardiac function in endotoxic shock.

OBJECTIVE: To evaluate the effect of continuous blood purification on cardiac function and plasma vasoactive substances in endotoxic shock in piglets. DESIGN: This was a randomized controlled trial in an animal laboratory in a tertiary care pediatric center. MATERIALS AND METHODS: Twenty-three healthy Shanghai white piglets weighing 8-14 kg were randomly assigned to one of the four groups: control group (n = 5), continuous blood purification without lipopolysaccharide infusion group (continuous blood purification, n = 6), lipopolysaccharide-induced endotoxin shock without continuous blood purification group (lipopolysaccharide, n = 6), and lipopolysaccharide-induced endotoxin shock with continuous blood purification group (continuous blood purification/lipopolysaccharide, n = 6). INTERVENTIONS: The lipopolysaccharide and continuous blood purification/lipopolysaccharide groups were injected intravenously with Escherichia coli endotoxin to induce septic shock. The continuous blood purification and continuous blood purification/lipopolysaccharide groups received continuous venovenous hemodiafiltration right after model establishment. At baseline state (T0), following the injection of lipopolysaccharide (T), 1 hr later (T1), 3 hrs later (T3), and 5 hrs later (T5) after model establishment, clinical systemic inflammatory response syndrome parameters, hemodynamic indexes, and plasma concentration of vasoactive substances were obtained. Plasma concentration of dopamine was measured by enzyme-linked immunosorbent assay (DSL Company) and endothelin-1 by enzyme-linked immunosorbent assay (R&D Company). Nitric oxide synthase activity was measured by chromatometry (Nanjing Jiancheng Bioengineering Institute, China). MEASUREMENTS AND MAIN RESULTS: In continuous blood purification/lipopolysaccharide group, after treatment with CPB, heart rate decreased significantly (p < .05) and pulse contour cardiac index, systematic vascular resistance index, and stroke volume index increased significantly (p < .05) when compared with lipopolysaccharide and continuous blood purification groups. After treatment with continuous blood purification, dopamine and endothelin-1 level increased and nitric oxide synthase activities decreased in continuous blood purification/lipopolysaccharide group when compared with the lipopolysaccharide group. In the continuous blood purification/lipopolysaccharide group, improvement in hemodynamic indexes was strongly correlated with increases in plasma dopamine and endothelin-1 level and decreases in nitric oxide synthase activity (r > .9, p < .05). CONCLUSIONS: The adverse cardiovascular effects of lipopolysaccharide-induced endotoxin shock can be improved by continuous blood purification. Improvement is correlated with increases in the concentration of plasma vasoactive substances (endothelin and dopamine) and decreases in nitric oxide synthase activity.

Mortality and morbidity of acute hypoxemic respiratory failure and acute respiratory distress syndrome in infants and young children.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) often develops acute respiratory distress syndrome (ARDS), and its incidence and mortalities in critically ill pediatric patients in China were 2% and 40% respectively. This study aimed at prospectively investigating incidence, causes, mortality and its risk factors, and any relationship to initial tidal volume (V(T)) levels of mechanical ventilation, in children £5 years of age with AHRF and ARDS. METHODS: In 12 consecutive months in 23 pediatric intensive care units (PICU), AHRF and ARDS were identified in those requiring > 12 hour intratracheal mechanical ventilation and followed up for 90 days or until death or discharge. ARDS was diagnosed according to the American-European Consensus definitions. The mortality and ventilation free days (VFD) were measured as the primary outcome, and major complications, initial disease severity, and burden were measured as the secondary outcome. RESULTS: In 13 491 PICU admissions, there were 439 AHRF, of which 345 (78.6%) developed ARDS, resulting in incidences of 3.3% and 2.6%, and corresponding mortalities of 30.3% and 32.8% respectively along with 8.2 and 6.7 times of relative risk of death in those with pneumonia (62.9%) and sepsis (33.7%) as major underlying diseases respectively. No association was found in V(T) levels during the first 7 days with mortality, nor for V(T) at levels < 6, 6 - 8, 8 - 10, and > 10 ml/kg in the first 3 days with mortality or length of VFD. By binary Logistic regression analyses, higher pediatric risk of mortality score III, higher initial oxygenation index, and age < 1 year were associated with higher mortality or shorter VFD in AHRF. CONCLUSIONS: The incidence and mortalities of AHRF and ARDS in children £5 years were similar to or lower than the previously reported rates (in age up to 15 years), associated with initial disease severity and other confounders, but causal relationship for the initial V(T) levels as the independent factor to the major outcome was not found.

[Recruitment maneuver in the treatment of young piglets with acute lung injury].

OBJECTIVE: To study the feasibility, efficiency and any benefits of recruitment maneuver (RM) in the facilitation of lung repair during recovery from ALI in acute lung injury (ALI) model of young piglets. METHODS: The piglet model of ALI was established by an intravenous injection of lipopolysaccharide (LPS). Twelve ALI piglets were randomly divided into two groups: conventional ventilation (CON) and RM with low tidal volume. Arterial blood gas, dynamic lung compliance (Cdyn) and systematic hemodynamics were monitored during the treatment. TGF-ß1 levels in bronchoalveolar lavage fluid (BALF) and plasma were measured. The mRNA expression of TGF-ß1 in the lungs was assessed by real time PCR. Lung tissue was examined for morphological changes. RESULTS: No significant difference was observed in cardiac output and peripheral vascular resistance (PVR) between the two groups. The extravascular lung water index (ELWI) from 6 hrs after ALI inducement and the pulmonary vascular permeability index (PVPI) 8 hrs after ALI inducement in the RM group decreased significantly compared with the CON group. Cdyn in the RM group increased quickly 1 hr after ALI inducement, and there was a significant difference between the two groups (P<0.05). P/F (ratio of PaO2 to FiO2) in the RM group was significantly higher than in the CON group from 2 hrs after ALI inducement (P<0.05). Alveolar-to-arterial oxygen difference in the RM group was obviously lower compared with the CON group from 2 hrs after ALI inducement (P<0.05). The levels of TGF-ß1 in plasma and BALF and the mRNA expression of TGF-ß1 in the lung tissue were lower than in the CON group. Volume density of alveolar aeration in the RM group was significantly higher than in the CON group, and the injury score in the RM group was lower (P<0.05). CONCLUSIONS: RM can improve gas exchange and Cdyn in the treatment of piglets with ALI. RM is a safe and effective approach to alveolar recruitment and can alleviate ventilation induced lung injury.

Effect of continuous veno-venous hemodiafiltration on endotoxin-induced acute lung injury of the piglets.

OBJECTIVE: To evaluate the effect of continuous veno-venous hemodialysis filtration (CVVHDF) on cardiopulmonary function and clearance of inflammatory mediators in piglets with endotoxin-induced acute lung injury. DESIGN: A randomized controlled trial. SETTING: An animal laboratory in a tertiary care pediatric center. SUBJECTS: : Eighteen piglets, weighing 6-8 kg. INTERVENTIONS: The piglets were anesthetized, ventilated, and received an intravenous infusion of 150 µg/kg of endotoxin. They were then randomly divided into three groups: control group (n = 6) received Ringer's lactate solution; the heparin group (n = 6) received heparin infusion plus Ringer's lactate solution; and the CVVHDF group (n = 6) received CVVHDF plus heparin infusion and Ringer's lactate solution. MEASUREMENTS AND MAIN RESULTS: Parameters measured simultaneously were: heart rate, mean arterial blood pressure, central venous pressure, pulse contour cardiac index, cardiac function index, left ventricular contractile index, and systemic vascular resistance index; extra vascular lung water index, respiratory rate, dynamic pulmonary compliance, airway resistance, Pao2/Fio2 ratio, serum tumor necrosis factor-α, and soluble tumor necrosis factor receptor. Lung tissue was obtained for pathologic lung injury scoring and wet/dry weight ratio. Endotoxin challenge decreased oxygenation and pulmonary mechanics, suppressed cardiac function, increased extravascular lung water, and elevated serum inflammatory mediators (tumor necrosis factor-α and soluble tumor necrosis factor receptor). After CVVHDF, pulmonary function and oxygenation improved (Pao2/Fio2, 291.5 ± 75.9 vs. 217.2 ± 45.4, respectively, p < .05); arterial blood pressure and cardiac function were restored (pulse contour cardiac index, 3.95 ± 0.52 L/min/m(2) vs. 2.69 ± 0.49 L/min/m(2), respectively, p < .05); extravascular lung water decreased, and serum inflammatory markers also decreased. Lung injury score improved and wet/dry weight ratio decreased. CONCLUSION: Early CVVHDF has a beneficial effect on acute lung injury in piglets and is associated with a reduction in inflammatory cytokines, improving pulmonary function and hemodynamics and decreasing extravascular lung water and lung damage.

[Clinical analysis of recruitment maneuver with low tidal volume in the treatment of 15 children with acute lung injury].

OBJECTIVE: To determine the effects and feasibility of recruitment maneuver (RM) on children with acute lung injury (ALI), and to establish a more reasonable ventilation strategy in the treatment of pediatric ALI. METHOD: A prospective physiologic study was conducted in the Pediatric Intensive Care Unit (PICU). Fifteen consecutive eligible pediatric patients with ALI according to the 1994 AECC definition were enrolled in this study. The children received the ventilation of RM with low tidal volume. The clinician administered RM was performed at 30 cm H2O continuous positive airway pressure (CPAP) for 30 seconds. RMs were conducted once every eight hours for five days. Data on gas exchange, lung mechanics and hemodynamics from pre-RM to post-RM (at 5, 15, 30 and 60 min) was recorded at the first, third and fifth day. To monitor the pathogenic conditions of children, the radiographic examination was rechecked for every child within one week. At last, we documented the mortality and the length of ventilation of every patient. RESULT: On the first, third and fifth day, the P/F ratio of the patients was 243.8 mm Hg, 281.8 mm Hg and 309.9 mm Hg respectively, and significant improvements in oxygenation were demonstrated post-RM compared to pre-RM (P < 0.01). Cdyn [0.762 ml/(cm H2O×kg), 0.835 (ml/cm H2O×;kg), 0.928 ml/(cm H2O×kg)] before RMs also showed increase in the children on the first, third and fifth day (P < 0.01). Though there were some changes in blood pressure and heart rate following RM, no statistically significant changes were found during the course of RM. During the entire study of 5 days, all the 11 subjects whose chest radiograph showed infiltration had improvements, the length of ventilation was (10.15 ± 4.3) d. CONCLUSION: RM can significantly improve the oxygenation and attenuate the deterioration in pulmonary function in treatment for pediatric ALI and improve the lung compliance. It is safe and feasible.

The epidemiology of acute respiratory distress syndrome in pediatric intensive care units in China.

OBJECTIVE: To assess the incidence of, predisposing factors for, and the rates and relative risks of mortality from acute respiratory distress syndrome (ARDS) in pediatric patients. DESIGN: A prospective study in 12 consecutive months from 2004 to 2005 in 25 pediatric intensive care units (PICUs). PATIENTS AND SETTING: ARDS was diagnosed according to the 1994 American-European Consensus Conference definitions, applied to all severely ill admissions between 1 month and 14 years of age. The PICUs were in major municipalities and provincial cities, and half were university affiliated. MEASUREMENTS AND RESULTS: From a total of 12,018 admissions, 7,269 were severely ill. One hundred and five (1.44%) patients developed ARDS and 64 (61.0%) died, which accounts for 13.2%, of the total ICU death (n = 485, 6.7%) or a nine times relative risk of dying. The median age at onset of ARDS was 24 months and 40% were less than 12 month old. Median time from PICU admission to the onset of ARDS was 16 h, and in 63% <24 h. Pneumonia (55.2%) and sepsis (22.9%) were the major predisposing factors for ARDS. These were respectively 14 and 5 times as high a death rate as those of the severely ill patients without ARDS. CONCLUSIONS: ARDS has a high mortality in these Chinese PICUs, especially in those with pneumonia and sepsis, and adequate management including lung protective ventilation strategy is required.

[Effect of continuous veno-venous hemodiafiltration on hemodynamics of piglets with endotoxin-induced acute lung injury].

OBJECTIVE: To investigate the effect of continuous veno-venous hemodiafiltration (CVVHDF) on endotoxin-induced acute lung injury (ALI) of piglets. METHODS: Eighteen piglets were randomly divided into three groups: control group (n = 6); heparin group (n = 6) and CVVHDF treatment group (n = 6). All the animals were anesthetized by muscle injection of ketamine (30 mg/kg), then placed in supine position, received continuous intravenous infusion of ketamine with the rate of 10 mg/(kgxh). After placing a 4.5 cm (inner diameter) tracheal tube via tracheostoma, controlled mechanical ventilation was established using the assisted-controlled ventilation option of the NEWPORT 200. Respiratory rate at 30 breath/min; PIP at 10 cm H2O (1 cm H2O = 0.098 kPa); PEEP at 2 cm H2O and fraction of inspired oxygen at 0.3. A vein catheter was placed into right vena jugularis interna to administer a Ringer's solution. Initially, at a rate of 10 ml/kg, followed by a rate of 15 ml/kg when the mean arterial blood pressure was below 70 mm Hg (1 mm Hg = 0.133 kPa), the rate of 20 ml/kg was used when the mean arterial blood pressure was below 60 mm Hg. An 8Fr double-lumen catheter was inserted into left femoral vein and served as the pathway for CVVHDF. A Pulsiocath Pcco catheter was positioned into left femoral artery to monitor the circulatory parameters. All catheters were flushed with heparinized saline to prevent clotting. Then all the animals were given intravenous infusion of 150 microg/kg endotoxin within 30 minutes to induce ALI. When the oxygenation index < 300 and pulmonary compliance < 30% of the baseline, the animals of heparin group received heparin infusion to maintain blood active coagulation time (ACT) 180 - 250 s, the animals of treatment group received CVVHDF with the blood flow of 50 ml/min, replacement rate of 300 ml/h, dialysis rate of 600 ml/h and the ultrafiltrate rate of 350 ml/h for six hours, heparin infusion to keep blood ACT 180 - 250 s. The circulatory parameters: heart rate (HR), mean arterial blood pressure (MABP), central venous pressure (CVP), pulse contour cardiac output index (PCCI); systemic venous resistance index (SVRI), cardiac function index (CFI), external venous lung water index (EVLWI), left ventricular contractile index (dPmx); respiratory parameters: respiratory rate (RR), pulmonary compliance (Cdyn) were monitored; arterial blood gas analysis was performed and oxygenation index (PaO2/FiO2) was calculated. All the parameters were recorded at baseline (B), onset of ALI (A 0 h), two hours (A 2 h), four hours (A 4 h), six hours (A 6 h) after ALI. RESULTS: No significant difference in circulatory parameters, respiratory parameters and blood gas analysis were found at B and A 0 h among the three groups. When the ALI occurred, PaO2/FiO2, Cdyn, MABP and PCCI of the three groups decreased; HR, RR, EVLWI, SVRI increased. After four hours of ALI, the RR, EVLWI, SVRI, CFI and dPmx of treatment group were improved, the differences were significant compared with the other two groups (P < 0.05). After six hours of ALI, the HR, PCCI, MABP, PaO2/FiO2 and Cdyn of treatment group were significantly improved, compared with control group and heparin group (P < 0.05). There were no significant differences in any of the parameters between control group and heparin group. The difference in CVP among three groups was not significant. CONCLUSION: CVVHDF has a good effect on hemodynamics of the endotoxin-induced ALI of the piglets.

[Therapeutic effect of continuous veno-venous hemodiafiltration on systemic inflammatory response syndrome induced by cecum perforate peritonitis in piglets].

OBJECTIVE: Most of the therapeutic strategies for systemic inflammatory response syndrome (SIRS) is not effective. This study was to investigate the effect of continuous veno-venous hemodiafiltration (CVVHDF) on SIRS induced by cecum perforate peritonitis in piglets. METHODS: Twelve piglets (weighing 7-9 kg) were randomly divided into two groups: control and CVVHDF (n=6). The piglets of both groups were subjected to a cecum puncture to induce peritonitis which caused SIRS. After SIRS occurred the piglets of the CVVHDF group immediately received the CVVHDF therapy for 6 hrs, with a blood flow rate of 20 mL/min, a replacement rate of 300 mL/h, and a dialysis rate of 600 mL/h. The heart rate (HR), mean artery blood pressure (MABP), respiratory rate (RR), arterial blood gas analysis and blood cells count were measured and recorded at baseline and onset of SIRS, and 2, 4 and 6 hrs after SIRS occurred. RESULTS: When SIRS occurred, the HR and RR increased and the MABP, artery oxygen pressure (PaO2) and the count of white cells decreased in both groups. The HR of the CVVHDF group decreased significantly at 2 hrs (P < 0.05) and remained lower until 6 hrs after CVVHDF therapy (P < 0.01) compared with that of the control group. The RR of the CVVHDF group was significantly lower than that of the control group 6 hrs after CVVHDF therapy (P < 0.05). The MABP of the CVVHDF group increased significantly 4 and 6 hrs after therapy compared with that of the control group (P < 0.01, P < 0.05 respectively). There were no significant differences in temperature, PaO2 and blood cells count between the two groups during the experiment. CONCLUSIONS: CVVHDF has a positive effect on hemodynamics in piglets with SIRS induced by cecum perforate peritonitis.

[Continuous blood purification therapy in 22 children with sepsis].

OBJECTIVE: Since continuous blood purification (CBP) has the effects of eliminating inflammatory mediators and improving organs function, CBP had been applied to treat non-renal diseases for nearly 10 years, but few studies have been conducted in children with sepsis and multiorgan dysfunction syndrome (MODS), especially in China. The present study aimed to evaluate the clinical effect of CBP in treatment of children with severe sepsis and MODS. METHODS: Twenty-two children with severe sepsis and MODS admitted to our PICU from Aug. 2003 to Aug. 2005 were treated with continuous veno-venous hemodialysis filtration. Their heart rate, arterial blood pressure, doses of vasoactive agents, spontaneous respiratory rate, PO2/FiO2 and prognosis were investigated. RESULTS: Catheterization and CBP were carried out in all the 22 children. Continuous vein-vein hemodialysis filtration (CVVHDF) and pre-dilution were chosen. The duration of CBP was (64.4 +/- 34.5) h. All the children had tachycardia before CBP and the heart rate fell gradually to 45 +/- 13 bpm 4 h after CBP. Blood pressure (BP) was stable in 7 children without shock during CBP. Ten children with early shock could maintain normal BP during CBP, but the doses of vasoactive agents were tapered 1 to 5 h after beginning of CBP and use of these agents was discontinued at 2 to 8 h. BP was elevated by (25.2 +/- 10.7) mmHg (1 mmHg = 0.133 kPa) in 5 refractorily shocked children 4 h after CBP and returned to normal level 8 h later. The doses of the vasoactive drugs were reduced at 2 to 8 h and ended 4 to 16 h later, which was longer than that of children with early stage shock. The accelerated spontaneous respiratory rate was slowed down by 7 +/- 4 per minute 4 h later, PO2/FiO2 rose from (177.7 +/- 53.1) mmHg before CBP to (341.0 +/- 60.2) mmHg 4 h after CBP in children with respiratory failure and reached the normal value (5.3 +/- 2.1) h later. FiO2 declined to less than 50%. Pediatric critical illness score was 62.2 +/- 7.4 on admission and elevated to (86.6 +/- 9.0) 24 h later, which was a significant elevation as compared to that of children with sepsis who were not treated with CBP seen between Aug. 2001 and July 2003. The survival rate was 72.7% after CBP and the effective rate of the treatment was 90.9%, but was 36% in children who were not treated with CVVHDF. CONCLUSION: CBP can effectively improve the vital organ's function of children with sepsis and MODS and raise their survival rate. Replacement fluid of modified Ports formula was useful for stability of serum potassium and sodium, but resulted in elevation of serum glucose, calcium, and osmolarity. The application of CBP in children with sepsis can lead to slight drop of blood pressure at the beginning and to bleeding during CBP.