Sirtuin 1 Mediates Hydrogen Sulfide-induced Cytoprotection Effects in Neonatal Mouse Cardiomyocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Current knowledge indicates that oxidative damage and the following inflammation is pivotal pathway for myocardial cell death. In recent decades, hydrogen sulfide (H2S) has been identified as a novel endogenous vasodilator and neuromodulator due to its antioxidation capacity. However, whether H2S pretreatment in neonatal mouse cardiomyocytes is a protection effect against oxidative stress remains elusive.</p><p><b>METHODS</b>Primary neonatal mouse cardiomyocytes were isolated and cultured, subsequently, pretreated with the H2S donor, sodium hydrosulfide (NaHS). Cell viability, lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) production are evaluated. The levels of superoxide dismutase (Sod2) and Sirtuin 1 (Sirt1), a deacetylation enzyme, were detected by Western blotting. The statistics was performed using independent-sample t-test.</p><p><b>RESULTS</b>NaHS (100 μmol/L) had no toxicity to primary neonatal mouse cardiomyocytes. Furthermore, NaHS pretreatment significantly improved neonatal mouse cardiomyocytes survival after H2O2-induced cell death, indicated by the decrease in LDH release (40.00 ± 2.65% vs. 65.33 ± 4.33%, P < 0.01) and ROS production (1.90 ± 0.33 vs. 4.56 ± 0.56, P < 0.05), and that the salubrious effect was accompanied by the upregulation of Sod2 expression. In addition, the study showed that NaHS pretreatment improved mitochondrial DNA number in neonatal mouse cardiomyocyte. Furthermore, the result demonstrated NaHS increased the expression of Sirt1 in neonatal mouse cardiomyocyte. Ex 527, an inhibitor of Sirt1, could attenuate these effects of NaHS-induced Sod2 expression and mtDNA number increase, furthermore, abrogate the cytoprotective effects of NaHS for neonatal mouse cardiomyocytes.</p><p><b>CONCLUSION</b>Sirt1 mediated H2S-induced cytoprotection effects in neonatal mouse cardiomyocytes.</p>

Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Animal models that demonstrate changes of renal function in response to acute lung injury (ALI) and mechanical ventilation (MV) are few. The present study was performed to examine the effect of ALI induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets.</p><p><b>METHODS</b>Twelve Chinese mini-piglets were randomly divided into two groups: the OA group (n = 6), animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALI induced by administration of OA, and the control group (n = 6), animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline.</p><p><b>RESULTS</b>Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALI, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6 ± 1.3) and (7.4 ± 1.5) times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group.</p><p><b>CONCLUSIONS</b>OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-α and IL-6 in plasma, lung and renal tissues.</p>

Total liquid ventilation reduces oleic acid-induced lung injury in piglets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. The aim of this study is to investigate the effect of total liquid ventilation on oleic acid (OA)-induced lung injury in piglets.</p><p><b>METHODS</b>Twelve Chinese immature piglets were induced acute lung injury by OA. Twelve piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes. Samples for blood gas analysis were collected before, and at 60-minute intervals after OA-induced lung injury. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were analyzed.</p><p><b>RESULTS</b>Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group (P < 0.05). The total lung injury score was also reduced in the study group (P < 0.05). The concentrations of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were significantly reduced in the study group (P < 0.05).</p><p><b>CONCLUSIONS</b>Total liquid ventilation reduces biochemical and histologic OA-induced lung injury in piglets.</p>

Surgical closure of apical multiple muscular septal defects via right ventriculotomy using a single patch with intermediate fixings / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multiple apical muscular ventricular septal defects (VSDs) remain a challenge for surgeons because of their anatomical features. We used single patch with intermediate fixations to repair multiple apical muscular VSDs through right ventriculotomy.</p><p><b>METHODS</b>We analysed the data of 16 children (median age 8 months, range 2 months to 144 months) with multiple apical muscular VSDs who underwent a single patch technique via apical right ventriculotomy. Perioperative data were collected and analysed, and the patients were followed up for three months to 66 months (median, 46 months) to investigate the outcomes.</p><p><b>RESULTS</b>All patients recovered from cardiopulmonary bypass easily with median of cardiopulmonary bypass time 87 minutes and of aortic crossclamp time 53 minutes. No surgically related death occurred and no patient required reoperation. One patient died of pseudomonas pyocyanea infection on day 11 postoperatively. Residual shunt happened in one patient with a diameter of 2 mm and spontaneously closed in 12 months after operation. Two patients presented slightly reduced right ventricular volume and apical hypokinesia postoperatively and recovered 24 and 36 months later respectively. No other complication was found during the three months to 66 months follow-up.</p><p><b>CONCLUSION</b>Our experiences using a single patch technique with intermediate fixations via right ventriculotomy in the management of multiple muscular VSDs had favourable outcomes.</p>

Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALI) in rats.</p><p><b>METHODS</b>Rats were randomly assigned to three groups (n = 6 in each group). Rats in the control group received a 0.9% solution of NaCl (1 ml × kg(-1) × h(-1)) by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously, and then the 0.9% NaCl infusion was restarted. Rats in the ALI group received a 0.9% NaCl solution (1 ml × kg(-1) × h(-1)) intravenous infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the 0.9% NaCl infusion was restarted. Rats in the hANP-treated ALI group received a hANP (0.1 µg × kg(-1) × min(-1)) infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels.</p><p><b>RESULTS</b>Serum interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours. The levels of all factors were significantly lower in the hANP treated rats (P < 0.005). Similarly, levels of IL-1β, IL-6, IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours. hANP treatment significantly reduced the levels of these factors in the lungs (P < 0.005). Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation.</p><p><b>CONCLUSION</b>hANP can attenuate inflammation in an OA-induced lung injury in rat model.</p>

Clinical results of combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital heart defects with intractable hypoplasia of the pulmonary arteries without intercourse or with intercourse stenosis is unsuitable for surgical correction or regular palliative procedures. We reported our experience with combined palliative procedures for congenital heart defects with intractable hypoplasia pulmonary arteries.</p><p><b>METHODS</b>From 2001 to 2012, a total of 41 patients with cyanotic congenital heart defects and intractable hypoplasia of the pulmonary arteries underwent surgical procedures. From among them, 31 patients had pulmonary atresia with ventricular septal defect (VSD) and the other 10 cases had complicated congenital heart defects with pulmonary stenosis. Different kinds of palliative procedures were performed according to the morphology of the right and left pulmonary arteries in every patient. If the pulmonary artery was well developed, a Glenn procedure was performed. A modified Blalock-Taussig shunt or modified Waterston shunt was performed if pulmonary arteries were hypoplastic. If the pulmonary arteries were severely hypoplastic, a Melbourne shunt was performed. Systemic pulmonary artery shunts were performed bilaterally in 25 cases. A systemic-pulmonary shunt was performed on one side and a Glenn procedure was performed contralaterally in 16 cases. Major aortopulmonary collateral arteries were unifocalized in six cases, ligated in two cases and interventionally embolized in two cases. There was one early death because of cardiac arrest and the hospital mortality was 2.4%.</p><p><b>RESULTS</b>Five patients suffered from postoperative low cardiac output syndrome, three had perfusion of the lungs, and two pulmonary infections. Systemic pulmonary shunts were repeated after the original operation in three cases due to the occlusion of conduits. The mean follow-up time was 25 months. The pre- and the post-operation left pulmonary indices were (8.13 ± 3.68) vs. (14.9 ± 6.21) mm(2)/m(2). The pre- and post-operation right pulmonary indices were (12.7 ± 8.13) vs. (17.7 ± 7.78) mm(2)/m(2). The pre- and post-operational pulmonary indices were (20.87 ± 9.43) vs. (32.6 ± 11.7) mm(2)/m(2). They were all significantly increased (P < 0.001). The diameter of the pulmonary artery increased after the modified Blalock-Taussig shunt ((5.51 ± 0.94) mm(2)/m(2) pre-operation vs. (7.01 ± 1.97) mm(2)/m(2) post-operation), the modified Waterston shunt ((5.70 ± 3.96) mm(2)/m(2) pre-operation vs. (9.17 ± 3.62) mm(2)/m(2) post-operation) and the Melbourne shunt ((2.17 ± 0.41) mm(2)/m(2) pre-operation vs. (7.35 ± 2.49) mm(2)/m(2) post-operation) (all P < 0.05). Bilateral pulmonary arteries developed well as compared to their pre-operation development. Hemoglobin decreased from (194 ± 27) to (174 ± 24) g/L (P < 0.05) and peripheral oxygen saturation increased from (65 ± 11)% to (84 ± 6)% (P < 0.001). During the follow-up of 27 to 49 months, ultimate complete repair was performed in four cases and one patient underwent a Glenn procedure.</p><p><b>CONCLUSIONS</b>The procedures should be considered on a case to case basis in patients having hypoplasia of the pulmonary arteries with cyanotic congenital heart defects. Combined palliative operations could be an adequate strategic treatment.</p>

Early prediction of acute kidney injury in infants and young children after cardiopulmonary bypass surgery / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the incidence of acute kidney injury (AKI) in infants and toddlers and evaluate the possibility of predicting AKI with urine neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), microalbumin (MA) and α1-microglobulin (α1-MG) after surgeries for congenital heart diseases with cardiopulmonary bypass (CPB).</p><p><b>METHOD</b>Fifty-eight children (ages ≤ 3 years) who had undergone surgery for congenital heart diseases with CPB were enrolled. Urinary samples were collected before and 4 h, 6 h, 12 h, 24 h post CPB to detect the concentration of NGAL, IL-18, NAG, MA and α1-MG.</p><p><b>RESULT</b>The AKI group had 29 cases, none AKI group also had 29 cases. Urinary concentration of NGAL 4, 6, and 12 h post CPB were significantly higher in AKI group (2820 µg/g, 905.7 µg/g, 76.1 µg/g separately) than in none AKI group (27.6 µg/g, 19.5 µg/g, 16.0 µg/g separately, P < 0.01). Urinary concentration of IL-18 4, 6, 12 and 24 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of NAG 4 h and 6 h post CPB were significantly higher in AKI group than in none AKI group (P < 0.01). Urinary concentration of MA/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.05). Urinary concentration of α1-MG/UCr post CPB 4 h, 6 h and 12 h were significantly higher in AKI group than in none AKI group (P < 0.01). All the five biomarkers had predictive abilities at 4-hour after surgery.</p><p><b>CONCLUSION</b>Urine biomarkers NGAL, IL-18, NAG, MA and α1-MG were valuable early predictors of AKI after CPB surgery.</p>

Comparative analysis of early and middle outcomes of the arterial switch operation in children with complete transposition of the great arteries with ventricular septal defect and severe pulmonary artery hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The best age for the arterial switch operation (ASO) in complete transposition of great arteries with ventricular septal defect is usually considered to be within six months. This is because of severe pulmonary arterial hypertension and pulmonary arterial obstructive pathological changes. There are few reports on ASO surgery in children older than three years old.</p><p><b>METHODS</b>We studied 41 children, including 24 males and 17 females, from January 2010 to December 2011. They were divided into three groups by operation age; 15 patients were < 1 year old, 13 were 1 - 3 years old, and 13 were > 3 years old. Associated cardiac abnormalities included patent ductus arteriosus in six cases, atrial septal defect in five cases, and mitral regurgitation in two cases. All the patients had echocardiography before the operation. Seventeen patients underwent a coronary computed tomography examination and five patients underwent right heart catheterization. All ASO surgeries were performed under inhalation anesthesia and hypothermic cardiopulmonary bypass.</p><p><b>RESULTS</b>Three operative deaths occurred. Two were in the < 1 year old group, who died from severe postoperative low cardiac output. The other was two years old and died of postoperative multiple organ failure. There was no significant difference in postoperative mortality and the recent mid-term survival rate among the three groups. Thirty-eight cases were followed up for an average of 11.2 months, ranging 6 - 20 months. One seven years old patient died of acute diarrhea and electrolyte disturbance arrhythmia caused by food poisoning. Three patients more than three years old still had residual pulmonary arterial hypertension.</p><p><b>CONCLUSION</b>Children older than three years old can still undergo the ASO procedure, but residual pulmonary hypertension is present.</p>

Lung microRNA profile in chronic cyanotic piglets with decreased pulmonary blood flow / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia, hypoxia, and others lead to infant morbidity and mortality more than acyanotic heart disease does. Despite the great effort of medical research, their genetic link and underlying microRNAs molecular mechanisms remain obscure. In this study, we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.</p><p><b>METHODS</b>Cyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding. Four weeks later, hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals. We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization. Furthermore, we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.</p><p><b>RESULTS</b>After surgical procedure 4 weeks later, the cyanotic model produced lower arterial oxygen tension, arterial oxygen saturation, and higher arterial carbon dioxide tension, hematocrit and hemoglobin concentration than controls (all P < 0.05). In 1273 miRNAs expressed in the immature piglets lungs, 2 most abundant microRNAs (miR-370 and miR-320) demonstrated significant difference between cyanotic and control group (all P < 0.05).</p><p><b>CONCLUSION</b>Our results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.</p>

Efficacy of sotalol hydrochloride on supraventricular tachycardia after surgery in children with congenital heart / 中华实用儿科临床杂志

Objective To observe the efficacy of sotalol hydrochloride on supraventricular tachycardia after surgery in children with congenital heart disease(CHD).Methods Twenty-one cases were observed from Sep.2005 to Mar.2012 from Beijing Anzhen Hospital Affiliated to Capital Medical University,who had sotalol hydrochloride for supraventricular tachycardia after CHD surgery.All patients were divided into 3 groups according to different dosage of sotalol hydrochloride,group Ⅰ:≤0.30 mg/(kg · dose),group Ⅱ:0.31-0.80 mg/(kg · dose),group Ⅲ:0.81-2.00 mg/(kg · dose).The efficacy,the heart rate (HR),systolic blood pressure (SBP),central venous pressure (CVP) were compared at different time.If bradycardia,long QT syndrome,torsade de pointes and other arrhythmia happened were observed.Results The efficacy were 16.7％,20.0％ and 100％ in group Ⅰ,group Ⅱ and group Ⅲ.The efficacy in group Ⅲ was the highest and there was statistical difference in 3 groups(P ＜0.05).The heart rate dropped separately 17.2％,21.5％,34.9％ in 3 groups and the HR in group Ⅲ was lower than group Ⅰ and group Ⅱ at different times,but it had statistically significant difference only at time of 8 hours after administration(P ＜ 0.05).The SBP and CVP dropped slightly and there was no statistical difference in SBP and CVP in 3 groups(all P ＞ 0.05).There were no bradycardia,long QT syndrome and torsade de pointes,etc.Conclusions Sotalol hydrochloride is a safe and effective drug with slight side effect on supraventricular tachycardia after CHD surgery.The higher the dose,the better the efficacy.

Clinical diagnosis and surgical treatment of diaphragmatic paralysis in infants with congenital heart disease after cardiac surgery / 中华实用儿科临床杂志

Objective To investigate the clinical manifestations,diagnosis and treatment of diagrammatic paralysis in infants with congenital heart disease (CHD) after cardiac surgery.Methods Thirty-one cases of diaphragmatic paralysis after cardiac surgery were selected from Jan.2006 to Jun.2012,including 23 cases were male and 8 cases were female.The age at operation was 20 days to 25 months,(8.0 ± 5.5) months on the average.The body weight at operation was 3.1-12.2 kg,(6.8 ± 2.3) kg on the average.All children received machine auxiliary breathing,and they had breathing difficulty without the machine.Diaphragmatic plication via 6-8 intercostal was performed under general anesthesia and endotracheal intubation.Lateral position,with uninjured side downward,was taken to perform chest posterolateral incision or chest lateral incision.Relaxing and weak diaphragm muscles were resected or directly sutured after folding.The clinical manifestations and diagnosis of children were summarized,and the effectiveness of diaphragmatic plication was evaluated.Results In 31 cases with diaphragmatic paralysis,there were 15 cases with left diaphragmatic paralysis,12 cases with right diaphragmatic paralysis,and 4 cases with bilateral diaphragmatic paralysis.Thirty-one cases had dyspnea after weaning of ventilator,and 28 cases received reintubation,23 cases with ventilator-as-sociated pneumonia,and 10 cases with tracheotomy.Diaphragmatic plication was performed in 28 cases,and all of them were weaned off ventilator successfully after the placation.The time of preoperative mechanical ventilation lasted 119-827 hours [(447 ± 225) hours],postoperative ventilator assistance time was 12-206 hours [(71 ± 52) hours],which showed significant difference in time of ventilation(P ＜0.05).Conservative treatment was given to the remaining 3 cases,and they were weaned off ventilation successfully with a better recovery.Conclusions Diaphragmatic paralysis in infants after CHD surgery affects their recovery.Diaphragm plication is a safe and effective method to treat the diaphragm paralysis.

Angiotensin-converting enzyme 2 activation protects against pulmonary arterial hypertension through improving early endothelial function and mediating cytokines levels / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Increasing evidences indicate that an activated renin-angiotensin system (RAS) causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension (PAH). Angiotensin-converting enzyme 2 (ACE2), a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet.</p><p><b>METHODS</b>Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction (RT-PCR), Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established.</p><p><b>RESULTS</b>Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure (PAP) started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines (tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6) and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis.</p><p><b>CONCLUSIONS</b>These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.</p>

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.</p><p><b>METHODS</b>Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified. ALI was induced in rats byoleic acid (OA), and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection.</p><p><b>RESULTS</b>The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge.</p><p><b>CONCLUSIONS</b>Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.</p>

Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pediatric patients are susceptible to lung injury. Acute lung injury in children often results in high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).</p><p><b>METHODS</b>Twelve Chinese immature piglets were induced acute lung injury by OA. The animals were randomly assigned to two groups of six animals, (1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.</p><p><b>RESULTS</b>Compared with MV group, the PLV group had better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2). PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P < 0.05).</p><p><b>CONCLUSION</b>PLV provides protective effects against TNF-α response in OA-induced acute lung injury in immature piglets.</p>

Fasudil inhibits platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation by up-regulation of p27kip¹ via the ERK signal pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>RhoA/Rho kinase (ROCK) pathway is involved in pulmonary arterial hypertension (PAH) and pulmonary artery smooth muscle cell (PASMC) proliferation. Inhibition of ROCK has been proposed as a treatment for PAH. But the mechanism of RhoA/ROCK pathway and its downstream signaling in proliferation of human PASMCs is unclear. We investigated the effect of fasudil, a selective ROCK inhibitor, on platelet-derived growth factor (PDGF) induced human PASMC proliferation, and the possible association between RhoA/ROCK and extracellular signal-regulated kinase (ERK), p27(Kip1).</p><p><b>METHODS</b>Human PASMCs were cultured with the stimulation of 10 ng/ml PDGF, and different concentrations of fasudil were added before the addition of mitogen. Cell viability and cell cycle were determined with MTT and flow cytometry respectively. ROCK activity, ERK activity and protein expression of proliferating cell nuclear angigen (PCNA) and p27(Kip1) were measured by immunoblotting.</p><p><b>RESULTS</b>By MTT assay, PDGF significantly increased the OD value that represented human PASMC proliferation, and pretreatment with fasudil significantly reversed this effect in a dose-dependent manner. After PDGF stimulation, the percentage of cells in S phase increased dramatically from 15.6% to 24.3%, while the percentage in G(0)/G(1) phase was reduced from 80.6% to 59%. And pretreatment with fasudil reversed the cell cycle effect of PDGF significantly in a dose-dependent manner. PDGF markedly induced ROCK activity and ERK activity with a peak at 15 minutes, which were significantly inhibited by fasudil. In addition, fasudil significantly inhibited PDGF-induced PCNA expression and fasudil also upregulated p27(Kip1) expression in human PASMCs, which decreased after PDGF stimulation.</p><p><b>CONCLUSION</b>RhoA/ROCK is vital for PDFG-induced human PASMC proliferation, and fasudil effectively inhibited PDGF-induced human PASMC proliferation by up-regulation of p27(Kip1), which may be associated with inhibition of ERK activity.</p>

Expression of ghrelin and insulin-like growth factor-1 in immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons. Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities. The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.</p><p><b>METHODS</b>Twelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured. Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction.</p><p><b>RESULTS</b>Four weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ± 15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12) mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P < 0.05). Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P = 0.004), and the plasma IGF-1 level was significantly lower than control (P = 0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P = 0.000), and the expression of IGF-1 mRNAs was elevated (P = 0.001).</p><p><b>CONCLUSIONS</b>Chronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and myocardial ghrelin mRNA expression were down-regulated in the chronic cyanotic immature piglets. The ghrelin system may be an important part of the network regulating cardiac performance.</p>

Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.</p><p><b>METHODS</b>Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n = 5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.</p><p><b>RESULTS</b>Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio, partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P < 0.05 or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P < 0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P < 0.05).</p><p><b>CONCLUSIONS</b>Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.</p>

A novel, stable and reproducible acute lung injury model induced by oleic acid in immature piglet / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Young children are susceptible to pulmonary injury, and acute lung injury (ALI) often results in a high mortality and financial costs in pediatric patients. A good ALI model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome (ARDS) more accurately and liberally. This study aimed to establish a hemodynamically stable and reproducible model with ALI in piglet induced by oleic acid.</p><p><b>METHODS</b>Six Chinese mini-piglets were used to establish ALI models by oleic acid. Hemodynamic and pulmonary function data were measured. Histopathological assessment was performed.</p><p><b>RESULTS</b>Mean blood pressure, heart rate (HR), cardiac output (CO), central venous pressure (CVP) and left atrial pressure (LAP) were sharply decreased after oleic acid given, while the mean pulmonary arterial pressure (MPAP) was increased in comparison with baseline (P < 0.05). pH, arterial partial pressure of O2 (PaO2), PaO2/inspired O2 fraction (FiO2) and lung compliance decreased, while PaCO2 and airway pressure increased in comparison with baseline (P < 0.05). The lung histology showed severe inflammation, hyaline membranes, intra-alveolar and interstitial hemorrhage.</p><p><b>CONCLUSION</b>This experiment established a stable model which allows for a diversity of studies on early lung injury.</p>

The analysis of the recent effectiveness of the total anomalous pulmonary venous connection repairs on infants / 中华外科杂志

<p><b>OBJECTIVE</b>To review the efficacy of total anomalous pulmonary venous connection (TAPVC) repair and to conclude the factors impacting the peri-operative death rate.</p><p><b>METHODS</b>The clinical data of 145 infants under 1 year old who underwent the TAPVC repair from January 2001 to July 2008 was analyzed. There were 94 male and 51 female patients. The mean age when the repair was performed was (7 ± 3) months, and the average weight was (6.3 ± 1.6) kg. As to the pulmonary connection type, 77 patients were supracardiac (53.1%), 47 patients were cardiac (32.4%), 9 patients were intracardiac (6.2%), and the remaining 12 patients were mixed (8.3%). Pre-surgery echocardiography showed that 21 patients had pulmonary venous obstruction (12 patients were supracardiac type, 3 patients were cardiac type, 3 patients were intracardiac type, and 3 patients were mixed type).</p><p><b>RESULTS</b>All patients underwent two-ventricle anatomy correction (the cases of complex malformations had been excluded). Peri-operative mortality was 11.7% (17/145). Because of the significant improvement in the surgical techniques, anesthesiology, cardiopulmonary bypass and the management of ICU in January 2006, the population was divided into two groups: A (before January 2006) and B (after January 2006). Peri-operative mortality decreased from 19.0% in group A to 6.2% in group B(P = 0.020). After analysis, it was determined that the factors impacting mortality were which group the patient belongs to, whether he/she had preoperative pulmonary vein obstruction and how big the atril septel connection was. The operative technique to keep the anastomotic aperture adequate and prophylaxis pulmonary hypertensive episodes contributed to the improvement on the mortality rate. There had been no case of repeating the surgery because of pulmonary venous obstruction during peri-operative care period.</p><p><b>CONCLUSIONS</b>Improvements of the surgical technique as well as the treatment in preoperative and postoperative have led to the reduction of the mortality. Preoperative pulmonary vein obstruction is still an important factor that contributes to early mortality.</p>

Effect of partial liquid ventilation on oleic acid-induced inflammatory responses in piglets / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pediatric patients are susceptible to lung injury. Acute lung injury (ALI) in children often results in a high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA).</p><p><b>METHODS</b>Twelve Chinese immature piglets were induced to develop ALI by oleic acid. The animals were randomly assigned to two groups (n = 6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.</p><p><b>RESULTS</b>Compared with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha both in plasma and tissue concentrations compared with MV group (P < 0.05).</p><p><b>CONCLUSIONS</b>Partial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.</p>