ObjectiveTo investigate the effect and incidence of residual leakage after surgical repair of large ventricular septal defects with moderate to severe pulmonary hypertension using cross-linkage mattress suture, a suture method invented by us, as compared with interrupted mattress suture. MethodsWe retrospectively analyzed the clinical data of 41 patients of large ventricular septal defect with moderate to severe pulmonary hypertension underwent surgery using cross-linkage mattress suture in Beijing Anzhen Hospital from February 2011 through April 2013. The 41 patients were as a cross-linkage group (average age 18.7±12.3 years, the ratio of male to female 31:10). Another 41 patients, who were repaired using interrupted mattress suture, were retrospectively chosen by matching age, size and location of the defects, pulmonary artery pressure and vascular resistance with members from the cross-linkage group, and were assigned as a control group (average age 17.4±11.8 years, the ratio of male to female 31:10). ResultsThere was no operative mortality and no new perioperative atrioventricular conduction block. Postoperative echocardiography revealed the incidence of residual leakage was 31.7% (13/41) in the control group, 0% (0/41) in the cross-linkage group with a statistical difference (χ2=13.164, P=0.000). With a follow-up of 18.2±6.1 months, no late death and no new atrioventricular conduction block occurred. There was no statistical difference in New York Heart Association functional class or pulmonary artery pressure measured through echocardiography between the two groups. While there was a statistical difference in incidence of residual leakage between the the cross-linkage group and the control group (0% (0/41) versus 26.8% (11/41), χ2=10.499, P=0.001). ConclusionThere is a high incidence of residual leakage after the surgical repair of large ventricular septal defect complicated with moderate to severe pulmonary hypertension using interrupted mattress suture, while the use of cross-linkage mattress suture can effectively reduce the incidence of residual leakage.
Pulmonary arterial hypertension is a kind of intractable disease which threatens human health severely. The results of operation are unsatisfactory. Clinical drug therapy is the major treatment which aims to relieve symptoms, improve the quality of life, and prevent the disease from progressing. Over the last several years, the studies of stem cells provide a new direction for the treatment of pulmonary arterial hypertension. It's demonstrated that the therapeutic effects of stem cells are better than that of the traditional methods. With the deepening of the researches, the therapy of stem cells is more and more compelling. The therapy of stem cells for pulmonary arterial hypertension is reviewed in this paper.
Objective To make an individualized treatment plan concerning a newborn with meconium aspiration syndrome combined with persistent pulmonary hypertension. Methods Based on the clinical questions raised by a newborn with meconium aspiration syndrome combined with persistent pulmonary hypertension, we searched The Cochrane Library (Issue 3, 2009), MEDLINE (1980 to June 2009), ACP Journal Club (1991 to June 2009), and Chinese Journal Fulltext Database (1994 to June 2009) for systematic reviews, randomized controlled trials (RCTs) and case-control studies. The quality of the included studies was assessed. Results A total of 9 RCTs, 1 health economic evaluation, 1 meta analysis, and 2 systematic reviews were considered eligible. The evidence indicated that the use of ECMO in infants of PPHN had shown a decreased risk of death, but not cost-saving from a societal perspective; iNO treatment could improve the PaO2 and resulted in a reduction in the incidence of requirement for ECMO; there were not randomized controlled trials regarding the treatment of PPHN by hyperventilation, high-frequency ventilation, alkali infusion, pulmonary vasodilators (magnesium sulfate, tolazoline, prostaglandin or prostacyclin, milrinone), surfactant therapy; oral sildenafil could lower oxygenation index (OI) and result in a reduction in the incidence of death. The individualized treatment plans of oral sildenafil were developed based on the available evidence, existing conditions of the hospital, and the values of children with families. After 1 month of treatment, the FiO2 returned to normal and symptoms were alleviated. Conclusion The treatment efficacies and the survival rates in meconium aspiration syndrome combined with PPHN have been improved by determining an individualized treatment plan according to evidence-based methods.
Objective To investigate the preventive effect of simvastatin，a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor，on hypoxic pulmonary hypertension and the relation between it and the angiotensin Ⅱ receptor-1（AT1R） expression in pulmonary arteriole.Methods Thirty male Sprague-Drawley rats were randomly allocated into three groups：a control group，a hypoxic group and a simvastatin preventive group.The animal model of hypoxic pulmonary hypertension was established by exposing the rats to normobaric hypoxic condition（8 h×6 d×3 w），and the preventive group were treated with simvastatin 10 mg/kg before hypoxic processing while the control and hypoxic groups were treated with sodium chloride.The mean pulmonary pressure（mPAP），serum cholesterol concentration，right ventricular hypertrophy index [RV/（LV+S）]，percentage of the wall thickness in the external diameter（WT%），percentage of the wall area in the total vascular area（WA%），and the AT1R expression in pulmonary arterioles were measured.Results When compared with the hypoxic group，in the preventive group，the mPAP and RV/（LV+S）obviously reduced [（22.6±3.86）mm Hg vs （29.3±2.27）mm Hg，（25.13±0.75）% vs （33.18±1.58）%，Plt;0.01 respectively]，the indices of wall thickness of rat pulmonary arteriole and area also decreased significantly [WT%：（15.98±1.96）% vs （25.14±1.85）%；WA%：（54.60±3.94）% vs 74.77±4.52）%；Plt;0.01 respectively]，and the positive degree of AT1R still lessened noticeably（1.23±0.09 vs 1.57±0.13，Plt;0.01）.All of the indices above in the hypoxic group increased markedly compared with the control group（Plt;0.01 respectively）.However，the differences of serum cholesterol among three groups were not significant（Pgt;0.05）.Conclusions Simvastatin can suppress the expression of AT1R in pulmonary vessel and prevent hypoxic pulmonary hypertension.
Objective To investigate the diagnosis and treatment of pulmonary arterial hypertension ( PAH) due to rare causes. Methods The clinical presentation, laboratory testing, diagnosis and treatment of 4 patients with PAH associated with rare causes in Beijing Anzhen Hospital from January 2001 to March 2008 were analysed retrospectively. Results Primary biliary cirrhosis, hyperthyroidism, antiphospholipid syndrome and pulmonary artery sarcoma may cause PAH, which were improved after corresponding diagnosis and management. Conclusion PAH can result from rare causes. The enhancement of its recognition will help earlier diagnosis and treatment and improve the prognosis.
Objective To investigate the role of Kv1. 5 in the pathogenesis of pulmonary hypertension simulated by hypobaria and hypoxia, and the effects of dichloroacetate ( DCA) on the Kv1. 5 expression in pulmonary arterial smooth muscle cells ( PASMCs ) and mean pulmonary arterial pressure ( mPAP) . Methods Twenty-four SD rats were randomly divided into a normal group ( N group) , a high altitude group ( HA group) , and a DCA treated group ( DCA group) . The N group were fed in normalconditions, the HA group and DCA group were fed in a hypobaria and hypoxia chamber simulated to an altitude of 5000 meters. In addition, the DCA group rats were gastric gavaged with DCA ( 70 mg · kg - 1 · d - 1 ) .Twenty-one days later, percentage of wall thickness ( WT% ) and percentage of wall area ( WA% ) of the pulmonary arteriole, mPAP, and the ratio of right ventricle / left ventricle and septum ( RV/ LV + S) were evaluated. Real-time PCR, immunohistochemistry and Western blot were carried out to detect the Kv1. 5 expression in PASMCs. Results In the HA group, WT% , and WA% of pulmonary arteriole, mPAP and RV/ ( LV + S) all increased significantly compared with the N group ( P lt;0. 01) . These changes in the DCA group were significantly lower than those in the HA group( P lt; 0. 01) . Furthermore, the protein and mRNA expression of Kv1. 5 in the PASMCs deceased significantly in the HA group compared with the N group( P lt;0. 01) , but recovered in the DCA group ( P lt;0. 01) . Conclusions The expression of Kv1. 5 in PASMCs is tremendously inhibited in rats fed in high altitude, which might be a important role of pulmonaryhypertension. DCA can inhibit the remodeling of pulmonary arterials probably by recovering Kv1. 5 expression.
Objective To investigate the dynamic expression of small ubiquitin-related modifiers-1 ( SUMO-1) in lung tissue in different phases of rat model of hypoxic pulmonary hypertension( HPH) .Methods Forty Wistar rats were randomly divided into 5 groups, and exposed to normoxia or to normobaric intermittent hypoxia for 3, 7, 14 or 21 days, respectively. Mean pulmonary arterial pressure( mPAP) , right ventricle hypertrophy index ( RVHI) , and the ratio of the vessel wall area to the total area( WA% ) weremeasured. RT-PCR and in situ hybridization were used to determine the mRNA expression of SUMO-1.Immunohistochemistry and Western blot were used to determine the protein expression of SUMO-1. Results The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 days of hypoxia,with WA% and mPAP significantly higher than those in the normal control. Pulmonary vascular remodeling aggravated with much higherWA% and mPAP afer 14 days of hypoxia, and reached the peak afer 21 days of hypoxia. SUMO-1 mRNA and protein expression markedly increased after 3 days of hypoxia, and reached peak after 14 days. After 21 days of hypoxia, SUMO-1 mRNA expression weakened but still higher than that in the normal control ( P lt; 0. 05) , and SUMO-1 protein expression remained stable. SUMO-1 mRNA and protein expression were positively correlated with mPAP, WA% and RVHI( all P lt; 0. 01) . Conclusion SUMO-1 is transcriptionally induced in lung tissue under chronic hypoxia, and thus involves in the pathogenesis of HPH.
Objective To investigate the effects of simvastatin on monocrotaline-induced pulmonary hypertension in rats, and explore the potential mechanism of simvastatin by blocking heme oxygenase-1( HO-1) expression. Methods 52 male Sprague-Dawley rats were randomly divided into five groups, ie. a control group, a simvastatin control group, a pulmonary hypertension model group, a simvastatin treatment group, a ZnPP ( chemical inhibitor of HO) group. Mean pulmonary arterial pressure ( mPAP) and right ventricular systolic pressure ( RVSP) were detected by right heart catheter at 5th week. Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysis system.Immunohistochemical analysis was used to investigate the expression and location of HO-1. HO-1 protein level in lung tissue were determined by western blot. Results Compared with the model group, simvastatin treatment decreased mPAP and RVHI significantly [ ( 35. 63 ±5. 10) mm Hg vs. ( 65. 78 ±15. 51) mm Hg,0. 33 ±0. 05 vs. 0. 53 ±0. 06, both P lt; 0. 05 ] . Moreover, simvastatin treatment partially reversed the increase of arterial wall area and arterial wall diameter [ ( 50. 78 ±9. 03 ) % vs. ( 65. 92 ±7. 19) % ,( 43. 75 ±4. 23) % vs. ( 52. 00 ±5. 35) % , both P lt; 0. 01) . In the model group, HO-1 staining was primarily detected in alveolar macrophages. Simvastatin treatment increased HO-1 protein expression significantly, especially in the thickened smooth muscle layer and alveolar macrophages. Inhibiting HO-1 expression using ZnPP resulted in a loss of the effects of simvastatin. mPAP in the ZnPP group was ( 52. 88±17. 45) mm Hg, while arterial wall area and arterial wall diameter were ( 50. 78 ±9. 03) % and ( 52. 00 ±5. 35) % , respectively. Conclusions Simvastatin attenuates established pulmonary arterial hypertension andpulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats. The effect of simvastatin is associated with HO-1.
【Abstract】 Objective To improve the knowledge of idiopathic pulmonary arterial hypertension ( IPAH) to elevate the levels of early diagnosis and treatment. Methods The clinical data of 39 IPAH patients admitted in Beijing Anzhen Hospital from October 1997 to June 2010 were reviewed. Results Of the 39 IPAH patients, 14 cases were male and 25 cases were female, with an average age of ( 29. 7 ±16. 4)years old. Main clinical manifestations were exertional dyspnea/breathlessness ( 90. 9% ) , chest tightness( 72. 7%) , chest pain ( 30. 7% ) , cough ( 41. 0% ) , fatigue ( 48. 7% ) , syncope ( 35. 9% ) , cyanosis( 28. 2% ) , edema of lower extremity ( 43. 6%) , etc. As revealed through echocardiography, 39 cases had a mean systolic pulmonary arterial pressure ( SPAP) of ( 88. 8 ±24. 2) mmHg, with right ventricle enlargementin 37 cases and normal in 2 cases. Pulmonary angiography showed central pulmonary arterial dilatation with pruning of the peripheral blood vessels in 36 cases and normal in 3 cases. Right heart catheterization and acute vasodilator testing was performed with iloprost in 15 patients, systolic pulmonary arterial pressure was( 77. 6 ±27. 8 ) mm Hg, and positive rate was 20. 0% . 24 cases were misdiagnosed at admission, and misdiagnosis rate was 61. 5% . The average time of misdiagnosis was ( 26. 0 ±24. 5) months. 20 cases were treated with general medical therapy and 1 case was managed with lung transplantation before April 2008.Then 13 cases were given pulmonary arterial hypertension-targeted therapies, including sidenafil, iloprost or bosentan. Two patients died in hospital with a mortality rate of 5. 1% . Conclusions IPAH is uncommon and often occurs in young and middle-aged women. The symptoms are nonspecific and easily misdiagnosed.Echocardiography and pulmonary angiography are helpful in diagnosis. Right heart catheterization and acute vasodilator testing should be carried out if available. The patients should be early treated with pulmonary arterial hypertension-targeted therapies. Lung transplantation may be an option for end-stage cases.