Vaccination in children with congenital heart disease: an observational study in a Beijing hospital.

INTRODUCTION: Underimmunization of CHD children is a public health concern in China. This study aimed to analyze the vaccination status of CHD children to provide additional evidence on optimal vaccination strategies and to make suggestions to promote appropriate vaccination services for these children. METHODS: This cross-sectional study evaluated 155 CHD children who received at least one vaccine at Peking University First Hospital. Vaccine-specific immunization rates were calculated. A telephone questionnaire survey was conducted that covered the following: the prognosis, reasons for delayed vaccinations and getting vaccination in the hospital. All statistical analyses were performed using the SPSS version 22 software. RESULTS: The left-to-right shunt group involved 138 children, while the other type CHD group involved 17. The vaccination rate was the highest for MPSV-AC (87.1%) and the lowest for DTaP (40.1%). The most frequent reason for vaccination in the hospital was refusal from community health centers (61.5%). No participant reported vaccine-related adverse effects. CONCLUSIONS: The age-appropriate vaccine-specific immunization rates in CHD children are low, with the lowest for DTaP. Refusal of community health centers was the primary reason. Our findings support that clinically stable CHD children may be safely vaccinated on a schedule similar to that of ordinary children in China. IMPACT: From our investigation, we found that the age-appropriate vaccine-specific immunization rates in children with CHD in China are low, with the lowest for diphtheria and tetanus toxoid and acellular pertussis. Refusal of community health centers to vaccinate was the primary reason for the low rates. We believe our study provides additional evidence on optimal vaccination strategies for children with CHD and it can be used to develop strategies to promote appropriate vaccination services for these children.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children.

BACKGROUND: We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD). METHODS: Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed. RESULTS: A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system. CONCLUSION: Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.

Gut microbiota analysis and its significance in vasovagal syncope in children.

BACKGROUND: Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance. METHODS: Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test. RESULTS: No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P < 0.05), and LEfSe analysis revealed Ruminococcaceae as a discriminative feature (linear discriminant analysis [LDA] score > 4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients. CONCLUSION: Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.

The configuration exchanging theory for transport properties and glass formation temperature of ionic liquids.

Understanding molecular motion in terms of molecular structure is an important issue for microscopic understanding of the nature of transport properties and glass transition, and for design of structured materials to meet specific demands in various applications. Herein, a novel molecular mechanism is proposed to connect macroscopic motion in ionic liquids with molecular structure via conformational conversions of the constituent ions or of the cation-anion pairs. New equations for description of relaxation time, diffusion coefficient, molar conductivity, and viscosity of ionic liquids are established. The equation parameters, which were determined from the temperature dependent heat capacities, self-diffusion coefficients, molar conductivities, and viscosities of typical ionic liquids, were used to produce predictions for the corresponding properties of other ionic liquids and for the glass transition temperatures of representative ionic liquids. All predictions are in nice agreements with the experimental results.

[Clinical analysis and follow-up study of cardiavascular system involvement in 10 children with methylmalonic aciduria combined with hyperhomocysteinemia].

OBJECTIVE: To study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC). METHODS: The clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up. RESULTS: In the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations. CONCLUSIONS: Metabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.

[Adrenomedullin alleviates collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary hypertension].

OBJECTIVE: To observe the effect of adrenomedullin (ADM) on the pulmonary vascular collagen metabolism in hypoxic rats in order to study the effect of ADM on chronic hypoxic pulmonary vascular structural remodeling and its possible mechanism. METHODS: Nineteen male Wistar rats were randomly divided into three groups: normal control (n=6), hypoxia (n=7) and ADM-treated hypoxia (n=6). ADM was subcutaneously administered into rats of the ADM-treated hypoxia group by mini-osmotic pump (300 ng/h) for two weeks. After two weeks of hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass[RV/ (LV+S)] was measured. The changes of pulmonary vascular microstructure were observed. Meanwhile, the expression levels of collagen I, collagen III and transforming growth factor (TGF)-ß in pulmonary arteries were detected by immunohistochemical assay. RESULTS: mPAP and RV/(LV+S) increased significantly in the hypoxia group compared with normal controls (P<0.01). The muscularization of small pulmonary vessels and the relative medial thickness of pulmonary arteries increased obviously in the hypoxia group compared with those in the normal control group (P<0.01). Meanwhile, the expression levels of collagen I, collagen III and TGF-ß of pulmonary arteries in the hypoxia group increased markedly compared with those in the normal control group. However, mPAP and RV/(LV+S) were significantly reduced in the ADM-treated hypoxia group compared with those in the hypoxia group (P<0.01). ADM ameliorated pulmonary vascular structural remodeling of hypoxic rats, with a decrease in the expression of collagen I, collagen III and TGF-ß of pulmonary arteries. CONCLUSIONS: ADM might play a regulatory role in the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular remodeling, through inhibiting the expression of TGF-ß and alleviating the collagen accumulation of pulmonary arteries.

[Clinical characteristics and follow-up study of tachycardia-induced cardiomyopathy in 12 children].

OBJECTIVE: Tachycardia induced cardiomyopathy (TIC), secondary to various tachyarrhythmias, is a reversible condition which can lead to cardiac enlargement and heart failure. The impairment of both structure and function of heart can be reverted completely or partially if tachyarrhythmias are ceased without delay. This study aimed to explore the clinical characteristics, therapeutic regimen and outcome of TIC in children. METHODS: Clinical data of 12 children with TIC, who came from Peking University First Hospital from Feb. 2003 to Jun. 2009, were retrospectively analyzed and followed up. The echocardiogram data on admission were compared with those from 12 homochronous cases with idiopathic dilated cardiomyopathy matched with 12 TIC cases in age and gender. RESULTS: Atrial tachycardia is the commonest arrhythmia in 12 TIC cases (75%). Four cases underwent catheterization for radiofrequency ablation and all succeeded. The cardiac rhythm of 6 out of 8 cases treated with drugs became sinus rhythm after 3 days to 2 weeks antiarrhythmic drugs treatment. The remaining 2 cases still retained atrial rhythm, but the ventricular heart rates declined to normal. The left ventricular end-diastolic dimensions of the 12 cases were decreased compared with those of pretherapy [(37.5 ± 5.3) mm vs. (43.0 ± 5.7) mm, P < 0.01], and the left ventricular ejection fractions were increased [(60.5% ± 5.6%) vs. (33.7% ± 10.3%), P < 0.01], after (3.4 ± 2.3) months. In our (4.3 ± 2.4) year-follow-up, all cases were fine, except in one case the tachyarrhythmia relapsed because of discontinuation of the drug treatment by her parents. The left ventricular end-diastolic dimensions in 12 TIC cases were smaller than those of the 12 age- and gender-matched idiopathic dilated cardiomyopathy [(43.0 ± 5.7) mm vs. (54.8 ± 7.5) mm, t = 7.9, P < 0.01], and the ejection fractions were higher [(33.7% ± 10.3%) vs. (21.8% ± 7.5%), t = 3.7, P < 0.01]. CONCLUSION: The diagnosis of TIC should be considered for the children with tachycardia, cardiac enlargement and cardiac insufficiency. The degree of cardiac enlargement and cardiac insufficiency might be of value for the differential diagnosis between TIC and idiopathic dilated cardiomyopathy. The rhythm control and ventricular rates control could all result in a favorite therapeutic efficacy.

[Genotype, phenotype analysis and follow-up study on patients with Duchenne/Becker muscular dystrophy].

OBJECTIVE: To improve the diagnosis and management of Duchenne/Becker muscular dystrophy(DMD/BMD). METHODS: Clinical features of 90 cases of DMD/BMD were collected. Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes, and multiplex ligation-dependent probe amplification (MLPA) was applied to detect DMD gene to identify genetic mutation. For those patients whose deletion/duplication mutation was not identified, FKRP gene mutation analysis was performed using PCR-DNA direct sequence. All the cases were followed up. RESULTS: Among the 90 cases of clinically diagnosed DMD/BMD, exons deletion of DMD was detected in 58 cases (64.44%), and exons duplication in 9 (10.00%). Among the 34 mothers with an affected boy but without previous genetic conformation, 17 were confirmed to be carriers with gene deletion/duplication. None of the 23 cases, without detected DMD gene deletion/duplication, carried FKRP gene mutation. Fourteen children were given short-term intermittent prednisone therapy (0.75 mg/kg daily during the first 10 days of each month). The course was not long enough and the sample size was too small to conclude any benefits or side effects. Prenatal diagnosis was provided for one mother in her next pregnancy detecting a female carrier fetus. CONCLUSION: DMD gene deletions mainly occurs between exons 45 and 54, while duplications mostly at 5'-terminus. Identification of the characteristics and types of gene mutation may facilitate the recognition and prognosis prediction of DMD/BMD. MLPA is a non-complex and quick diagnostic tool for DMD/BMD and its carriers, and also helpful in genetic counseling.

[Clinical characteristics of cardiac syncope in children].

OBJECTIVES: To explore the clinical characteristics of cardiac syncope (CS) in children, and understand their significance in predicting the cardiac syncope. METHODS: Twenty-three patients were referred to our department for evaluation of syncope. The diagnosis of the above cases was cardiac syncope. Each patient was interviewed using a standard questionnaire. The clinical histories and standard baseline electrocardiogram were analyzed to identify the variables contributing to the diagnosis of CS in children. RESULTS: A cardiac cause was identified in 23 syncopal patients presenting to the Department of Pediatrics, Peking University First Hospital: sick sinus syndrome in 7, congenital long QT syndrome in 4, third degree atrioventricular block in 2, supraventricular tachycardia in 2, ventricular tachycardia in 1, atrial fibrillation in 1, pacemaker dysfunction in 1, idiopathic pulmonary hypertension in 3, hypertrophic cardiomyopathy in 1, and dilated cardiomyopathy in 1. The average age of CS patients was 9 years. In totally 23 patients, exertion related syncope spells were found in 14 cases (60.9%), syncope spells at various position 7/23 (30.4%), absence of prodromes in 12/23 (52.2%), syncope spells with incontinence in 4/23 (17.4%), history of heart disease in 4/23 (17.4%). Abnormal standard baseline electrocardiogram was found in 21 cases (91.7%). CONCLUSIONS: The children with cardiac syncope have overt clinical features, especially abnormal findings in electrocardiogram and exertion related syncope spells are the most common clinical features.

[Clinical characteristics and therapy of severe Mycoplasma pneumonia in children].

OBJECTIVE: To study the clinical characteristics, therapeutic regimen and outcome of severe Mycoplasma pneumonia (MP) in children. METHODS: Clinical data of 79 children with MP, including 69 mild and 10 severe cases, were retrospectively analyzed. The 10 children with severe MP were followed-up. RESULTS: In severe MP cases, the fever duration prior to hospitalization and the total fever duration were more prolonged, peripheral blood leucocytes counts, C-reactive protein and erythrocyte sedimentation rate increased, and serum IgM and IgE levels increased as compared to mild MP cases. Of the 10 cases of severe MP, 4 manifested as pulmonary consolidation, 4 as pulmonary consolidation complicated by moderate to large pleural effusion and 2 as progressively worsening pulmonary radiographic findings. Nine severe MP cases were administered with glucocorticoid as well as antibiotics, and the therapeutic effect was satisfactory. In the convalescence stage, bronchofiberoscope lavages were used in 5 severe cases because of persistent pulmonary consolidation. CONCLUSIONS: Severe MP was characterized by rapid progression, pulmonary consolidation, moderate to severe pleural effusion, obviously increased inflammatory indexes, and poor therapeutic reaction to simple macrolide antibiotics. Besides antibiotics, glucocorticoid should be used for severe MP cases as soon as possible. For severe cases with persistent pulmonary consolidation, bronchofiberoscope lavages are recommended.

[Alterations of proadrenomedullin N-terminal 20-peptide in rats with pulmonary hypertension induced by high pulmonary blood flow].

OBJECTIVE: The mechanism of high pulmonary blood flow-induced pulmonary hypertension remains unclear. The aim of this study was to explore the effect of proadrenomedullin N-terminal 20-peptide (PAMP) on pulmonary hypertension, through examining the alterations of pulmonary PAMP expression and plasma PAMP concentration in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Sixteen male Sprague-Dawley rats were randomly divided into control (n=8) and shunt groups (n=8). Aortocaval shunting was produced in the shunt group. After 11 weeks of shunting, systolic pulmonary artery pressure (sPAP), diastolic pulmonary artery pressure (dPAP) and mean pulmonary artery pressure (mPAP) were evaluated by using a right cardiac catheterization procedure. The ultrastructural changes in intra-acinar pulmonary arteries were observed. The concentration of plasma PAMP was measured by radioimmunoassay. The expression of PAMP in pulmonary arteries was detected by immunohistochemical assay. RESULTS: sPAP, dPAP and mPAP were significantly increased in shunt rats compared with controls (P < 0.01). Ultrastructural changes, such as hyperplasia and swelling of endothelial cells, irregularity of internal elastic laminar, and hypertrophy and increased number of synthetic phenotype of smooth muscle cells, were found in intra-acinar pulmonary muscularized arteries in the shunt group. Plasma PAMP concentration (616 +/- 195 pg /mL vs 427 +/- 90 pg /mL) and PAMP expression in endothelial cells (0.62 +/- 0.09 vs 0.38 +/- 0.12) and in smooth muscle cells (0.24 +/- 0.07 vs 0.14 +/- 0.05) of pulmonary arteries increased significantly in the shut group compared with controls. CONCLUSIONS: The up-regulation of pulmonary and plasm PAMP expression might be involved in the development of high pulmonary blood flow-induced pulmonary hypertension.

Imbalance of endogenous homocysteine and hydrogen sulfide metabolic pathway in essential hypertensive children.

BACKGROUND: Hypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension. METHODS: Twenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio. RESULTS: Plasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05. CONCLUSION: There was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.

Chronic administration of adrenomedullin attenuates hypoxic pulmonary vascular structural remodeling and inhibits proadrenomedullin N-terminal 20-peptide production in rats.

Adrenomedullin (ADM) is a novel cardiovascular-active peptide involved in vasodilation, reducing blood pressure and inhibiting vascular smooth muscle cell migration and proliferation. Previous research showed that ADM might be involved in the development of pulmonary hypertension. In this study, we investigated the effect of ADM subcutaneously administered by mini-osmotic pump (300 ng/h) on pulmonary hemodynamics and pulmonary vascular structure in hypoxic rats, as well as the influence of ADM on the proadrenomedullin N-terminal 20-peptide (PAMP) protein and mRNA expressions and its plasma concentrations. The results showed that ADM obviously decreased mean pulmonary artery pressure and the ratio of right ventricular mass to left ventricular plus septal mass in hypoxic rats. Chronic infusion of ADM lessened the muscularization of small pulmonary vessels, attenuated relative medial thickness and relative medial area of pulmonary arteries, and alleviated the ultrastructural changes in pulmonary arteries of hypoxic rats. ADM inhibited the proliferation of pulmonary artery smooth muscle cells, represented by a decrease in the expression of proliferative cell nuclear antigen (PCNA) in the pulmonary artery. Meanwhile, plasma PAMP concentration and the expression of PAMP protein and mRNA by pulmonary arteries in rats of hypoxia with ADM group were markedly decreased compared with those in hypoxic group. The results suggest that ADM ameliorated the development of hypoxic pulmonary vascular structural remodeling. Intramolecular regulation of ADM may play an important role in the regulation of hypoxic pulmonary hypertension by ADM.

[Effect of adrenomedullin 1-50 on chronic hypoxic pulmonary hypertension in rats].

OBJECTIVE: To explore the effect of adrenomedullin(1-50) (ADM(1-50)) on hypoxic pulmonary hypertension and pulmonary vascular structural remodeling and the plasma concentration of nitric oxide (NO) and hydrogen sulfide (H(2)S) in rats. METHODS: Twenty male Wistar rats were randomly divided into control group (n=7), hypoxic group (n=6) and hypoxic with ADM(1-50) group (n=7). ADM(1-50) was subcutaneously administered into rats of hypoxic with ADM(1-50) group by mini-osmotic pump (300 ng/h). After two weeks' hypoxic challenge, mean pulmonary arterial pressure (mPAP) was evaluated by using a right cardiac catheterization procedure. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+S)] was detected. Pulmonary vascular microstructure was measured and the ultrastructural changes in intra-acinar pulmonary arteries were observed. Meanwhile, plasma concentrations of NO and H(2)S were measured. RESULTS: mPAP was significantly increased in hypoxic rats than that in controls [(24.9+/-6.8) mmHg vs (14.3+/-2.4) mmHg, P<0.01,1 mmHg=0.133 kPa]; RV/(LV+S) was also significantly increased in hypoxic rats than that in controls [(0.318+/-0.054) vs (0.182+/-0.007), P<0.01]. Microstructure and ultrastructure of pulmonary arteries changed obviously in hypoxic rats with the development of hypoxic pulmonary vascular structural remodeling. Meanwhile, plasma NO and H(2)S concentrations in hypoxic rats were markedly decreased compared with controls. However, mPAP was significantly decreased in hypoxic rats treated with ADM(1-50) than that in hypoxic rats [(14.9+/-3.0) mmHg vs (24.9+/-6.8) mmHg, P<0.01]; RV/(LV+S) was also significantly decreased than that in hypoxic rats [(0.185+/-0.011) vs (0.318+/-0.054), P<0.01]. ADM(1-50) ameliorated pulmonary vascular structural remodeling of hypoxic rats in association with an increase in plasma NO and H(2)S concentrations. CONCLUSION: ADM(1-50) plays an important role in regulation of the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular structural remodeling, through promoting NO and H(2)S production in hypoxic rats.

Effect of L-arginine on pulmonary artery smooth muscle cell apoptosis in rats with hypoxic pulmonary vascular structural remodeling.

This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

[Regulation of endogenous cystathionine-gamma-lyase gene expression in high pulmonary flow by nitric oxide precursor].

AIM: Pulmonary hypertension is a common complication of congenital heart disease with a left-to right shunt. The mechanism of pulmonary hypertension induced by high pulmonary blood flow is still not fully understood. Recent studies showed that hydrogen sulfide (H2S) could relax vascular smooth muscle cells. But the change of the system of H2S in pulmonary hypertension induced by high pulmonary blood flow was not reported. We studied the influence on expression of CSE mRNA and production of hydrogen sulfide in rat lung tissues by L-Arginine, in order to demonstrate a regulating role of nitric oxide (NO) in the regulation of cystathionine-gamma-lyase/hydrogen sulfide system (CSE/H2S). METHODS: Thirty male SD rats were randomly divided into shunting group, shunting with L-Arginine group, and control group. Abdominal aorta and inferior vena cava shunting was produced in rats of the later group. Pulmonary artery mean pressure (mPAP) and the hypertrophy of right ventricle of each rat were analyzed. The expression of lung tissue CSE mRNA was measured using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. The activity of CSE in lung tissue was measured according to chemical analysis. RESULTS: mPAP was significantly increased in shunted rats compared with normal control (P < 0.01), the expression of lung tissue CSE mRNA and the activity of CSE in lung tissue were decreased in shunt group (P < 0.01). However, L-arginine significantly attenuated pulmonary artery pressure, but augmented the expression of lung tissue CSE mRNA as well as the activity of CSE in lung tissue. CONCLUSION: L-Arginine reverses the down-regulation of CSE/H2S system in high pulmonary blood flow-induced pulmonary hypertension.

[Impact of high pulmonary blood flow on pulmonary vascular structure and human urotensin II in intrapulmonary arteries of rats].

AIM: To study human urotensin II (hUII) expression in intrapulmonary arteries of rats with pulmonary hypertension induced by high pulmonary blood flow and explore the role of hU II in the development of pulmonary hypertension induced by left to right shunt. METHODS: Aortocaval shunting was produced for 11 weeks in rats. Pulmonary artery mean pressure (PAMP) of each rat was evaluated using right cardiac catheterization. The pulmonary vascular structural changes, including the percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of intra-acinar pulmonary arteries were examined. Meanwhile, the expression of hU II by pulmonary arteries was detected by immunohistochemistry. RESULTS: After 11-week aortocaval shunting, PAMP was significantly increased. The percentage of muscularized arteries of small pulmonary vessels and relative medial thickness of pulmonary arteries were obviously increased in shunting rats compared with controls (P < 0.01, respectively). Meanwhile, hU II expression by pulmonary artery endothelial cells and smooth muscle cells was significantly augmented in rats of shunt group, which was positively correlated with PAMP and the structural changes in pulmonary arteries. CONCLUSION: The up-regulation of hU II in pulmonary arteries might be involved in the development of pulmonary vascular structural remodeling and pulmonary hypertension induced by high pulmonary blood flow.

[Endogenous nitric oxide pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling].

OBJECTIVE: Pulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left-to-right shunt. However, the mechanism is still not clear. The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow. METHODS: Sixteen male SD rats were randomly divided into control group (n = 8) and shunting group (n = 8). Aortocaval shunting was produced for 11 weeks in shunt rats. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] was detected. Pulmonary vascular micro-and ultra-structure was examined by using a light microscope and a transmitted electronic microscope. Meanwhile, the concentration of plasma NO was measured by spectrophotometry. The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively. RESULTS: After 11-week aortocaval shunting, mPAP was significantly increased [(22.5 +/- 2.6) mmHg vs. (15.8 +/- 2.8) mmHg, 1 mmHg = 0.133 kPa, t = 4.97, P < 0.01], and RV/(LV + S) was also markedly increased (0.267 +/- 0.022 vs. 0.221 +/- 0.016, t = 4.85, P < 0.01). The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23.2 +/- 2.4)% vs. (13.5 +/- 2.1)%, t = 7.82, P < 0.01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery: (7.76 +/- 0.56)% vs. (4.82 +/- 1.03)%, t = 6.23, P < 0.01; small pulmonary artery: (11.94 +/- 0.66)% vs. (6.91 +/- 0.53)%, t = 14.96, P < 0.01]. Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased [(30.2 +/- 7.9) micromol/L vs (19.7 +/- 5.7) micromol/L, t = 3.05, P < 0.01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group. CONCLUSION: The upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling.