Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Extracorporeal membrane oxygenation as a bridging therapy for patients with thiamine deficiency-induced pulmonary arterial hypertension

Thiamine deficiency is characterized by a deficiency of thiamine(vitamin B1),lactic acidosis,pulmonary arterial hypertension(PAH),right-sided heart failure,and peripheral nerve damage.Thiamine deficiency is easily misdiagnosed and missed during clinical practice and is associated with death in severe cases.[1,2]Here we reported a patient who was admitted to the hospital with severe metabolic acidosis and pulmonary hypertension and finally diagnosed with thiamine deficiency by detecting plasma vitamin B1 levels.Since clinically obvious thiamine deficiency is rare,and cases of thiamine deficiency requiring extracorporeal membrane oxygenation(ECMO)treatment are rarer,we believe that our case will be helpful for emergency clinicians.

Effects of combined aerobic,resistance and inspiratory training in patients with pulmonary hypertension:A systematic review

BACKGROUND Pulmonary hypertension(PH)is a serious progressive disorder of the modern world,characterized by endothelial dysfunction and impaired vasoreactivity.Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity.Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities.However,data regarding the effects of combined exercise training programs in patients with PH still remains limited.AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.METHODS Our search included all available randomized controlled trials(RCTs)regarding combined aerobic,resistance and inspiratory training programs in patients with PH in 4 databases(Pubmed,PEDro,Embase,CINAHL)from 2012 to 2022.Five RCTs were included in the final analysis.Functional capacity,assessed by peak VO_(2)or 6-min walking test(6MWT),as well as quality of life,assessed by the SF-36 questionnaire,were set as the primary outcomes in our study.RESULTS Peak VO_(2)was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs.Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs(P<0.05).Quality of life was measured in 4 out of 5 RCTs.Although patients improved their quality of life in each group,however,only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.CONCLUSION By this systematic review,we have demonstrated that combined aerobic,resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH.Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Pulmonary Hypertension Crisis in Patient with Tetralogy of Fallot and Mixed Total Anomalous Pulmonary Vein Connection after the Primary Correction:A Rare Case Report

Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.

“Treat-Repair-Treat”:Management of Left Main Coronary Compression by a Pulmonary Artery Aneurysm in a Patient with Atrial Septal Defect and Significant Pulmonary Hypertension

Left main coronary compression syndrome(LMCS)may complicate pulmonary artery aneurysms(PAA),usually developed in the context of pulmonary arterial hypertension(PAH).We report the case of a 51-year-old female patient with an atrial septal defect(unsuitable for device closure)complicated by a PAA generating a 90%left main stenosis.The significant PAH held us back from immediate surgery.After specific dual PAH-targeted therapy(sildenafil and bosentan),the atrial septal defect could be closed with a unidirectional valved patch;the PAAinduced LMCS was treated by reductive arterioplasty.The postoperative course was uneventful.Follow-up showed clinical improvement,but PAH treatment was still needed.After three months,coronary angiography showed only an insignificant residual left main stenosis,proving that reductive pulmonary arterioplasty was effective in treating LMCS.Any PAA requires further evaluation for LMCS,a dangerous but treatable complication.The“treat-repair-treat”strategy and shunt-closure with a unidirectional valved patch can both improve surgical prospects of LMCS with shunt-related PAH.

Cardiac amyloidosis presenting as pulmonary arterial hypertension:A case report

BACKGROUND Pulmonary hypertension is a rare cardiopulmonary disease,with an insidious onset that usually worsens rapidly.Amyloid light chain(AL)amyloidosis is a rare systemic disease caused by extracellular deposition of pathologic,insoluble,and proteinaceous fibrils in organs and tissues;however,it is difficult to diagnose given its varied and nonspecific symptoms.To date,rare cases of amyloidosis with pulmonary hypertension have been reported.Of note,the optimal treatments for cardiac amyloidosis complicated with pulmonary hypertension remain unclear.CASE SUMMARY We report a case of a 51-year-old woman who presented with progressively worsening dyspnea.Transthoracic echocardiography indicated severe pulmonary hypertension.Twenty-seven months after first admission,the patient returned with symptoms of progressive heart failure.A myocardial tissue sample stained with Congo red was positive,and the patient was ultimately diagnosed with AL amyloidosis with cardiac involvement.CONCLUSION Although pulmonary hypertension may be idiopathic,it is frequently associated with other conditions.In rare cases,pulmonary hypertension can be a complication of AL amyloidosis,which should be seriously considered in any adult presenting with nonspecific signs or symptoms of cardiac distress.

Rutaecarpine attenuates monocrotaline-induced pulmonary arterial hypertension in a Sprague-Dawley rat model

Background:Pulmonary arterial hypertension presents with obliterative remodeling of the pulmonary arteries and progressive elevation of pulmonary vascular resistance,which increase the risk of right ventricular failure and death.It has been reported in previous studies that rutaecarpine plays a crucial role in anti-inflammatory and antioxidant activities,which may help regulate cell apoptosis and cell proliferation.The purpose of this study was to determine the effects of rutaecarpine in the rat model of monocrotaline-induced pulmonary hypertension.Methods:We induced pulmonary arterial hypertension in adult Sprague-Dawley rats by injecting monocrotaline(60 mg/kg)and then treated with rutaecarpine(40 mg/kg·d)or sildenafil(30 mg/kg·d)(positive control).Subsequently,pulmonary function,inflammation,cytokines and pulmonary vascular remodeling or proliferation were assessed.Results:Rutaecarpine was found to improve monocrotaline-induced mean pulmonary artery pressure,cardiac index,right heart index,right ventricular hypertrophy index,pulmonary artery remodeling and pulmonary function.reverse transcription-quantitative polymerase chain reaction demonstrated a decrease in tumor necrosis factor-α,interleukin-6 and interleukin-1β,whereas western blots a significantly decrease in the expression of nuclear factor kappa-B,endothelin-1,extracellular signal-regulated kinases 1/2,B cell lymphoma-2,Beclin1 and microtubule-associated protein1 light chain 3-II protein,and increase in the expression of Bax,caspase-3 and p62 protein.Conclusion:Rutaecarpine attenuated pulmonary arterial hypertension by inhibiting inflammation,oxidative stress,cell proliferation and autophagy,while promoting apoptosis.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Twin pregnancy with sudden heart failure and pulmonary hypertension after atrial septal defect repair: A case report

BACKGROUND Pulmonary arterial hypertension(PAH)in pregnancy is one of the major obstetric complications and is considered a contraindication to pregnancy as it is classified as a class IV risk in the revised risk classification of pregnancy by the World Health Organisation.Pregnancy,with its adaptive and expectant mechanical and hormonal changes,negatively affects the cardiopulmonary circulation in pregnant women.Do patients with repaired simple congenital heart disease(CHD)develop other pulmonary and cardiac complications during pregnancy?Can pregnant women with sudden pulmonary hypertension be treated and managed in time?In this paper,we present a case of a 39-year-old woman who underwent cesarean section at 33 wk'gestation and developed PAH secondary to repaired simple CHD.Our research began by a PubMed search for"pulmonary hypertension"and"pregnancy"and"CHD"case reports.Three cases were selected to review PAH in pregnancy after correction of CHD defects.These studies were reviewed,coupled with our own clinical experience.CASE SUMMARY Herein,a case involving a woman who underwent atrial septal defect repair at the age of 34,became pregnant five years later,and had a sudden onset of PAH and right heart failure secondary to symptoms of acute peripheral edema in the third trimester of her pregnancy.As a result,the patient underwent a cesarean section and gave birth to healthy twins.Within three days after cesarean delivery,her cardiac function deteriorated as the pulmonary artery pressure increased.Effec-tive postpartum management,including diuresis,significant oxygen uptake,vasodilators,capacity and anticoagulants management,led to improvements in cardiac function and oxygenation.The patient was discharged from hospital with a stable recovery and transferred to local hospitals for further PAH treatment.CONCLUSION This case served as a reminder to obstetricians of the importance of pregnancy after repair of CHD.It is crucial for patients with CHD to receive early correction.It suggests doctors should not ignore edema of twin pregnancy.Also,it provides a reference for the further standardization of antenatal,in-trapartum and postpartum management for patients with CHD worldwide.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography

BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension(CTEPH),approximately 20%-29%of patients exhibit a restrictive pattern on pulmonary function testing.AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area(CSA)in patients with CTEPH.METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019,we evaluated 15 patients with CTEPH who had chest computed tomography(CT)performed at baseline and after at least 6 mo of therapy.We matched the CTEPH cohort with 45 control patients by age,sex,and observation period.CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.RESULTS Total,right lung,and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline(total,P=0.004;right lung,P=0.003;right lower lobe;P=0.01).In the CTEPH group,the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group(total,P=0.01;right lung,P=0.007;right lower lobe,P=0.01;CSA,P=0.0002).There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.CONCLUSION After at least 6 mo of treatment,CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

A rare cause of pulmonary hypertension in an elderly woman

Diastolic dysfunction is a common substrate of pulmonary hypertension(PH) in the elderly.A minority of them,however,has another etiology of PH with diastolic dysfunction as a confounder,the alarming echocardiographic features of which are important to recognize.For example,dilated coronary sinus is unusual,as is significantly dilated right atrium.

Research progress in the etiology of pulmonary hypertension

Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.

Prevalence of pulmonary hypertension among children with Down syndrome:A systematic review and meta-analysis

BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension:State of the art

Chronic thromboembolic pulmonary hypertension(CTEPH)is a complex chronic disease in which pulmonary artery stenosis or obstruction caused by organized thrombus can lead to increased pulmonary artery pressure and pulmonary vascular resistance,ultimately triggering progressive right heart failure and death.Currently,its exact mechanism is not fully understood.Pulmonary endarterectomy(PEA)has immediate effects with low perioperative mortality and satisfactory prognosis in experienced expert centers for CTEPH patients with proximal lesions.Nevertheless,37%of patients are deemed unsuitable for PEA surgery due to comorbidities and other factors,and nearly half of the operated patients have residual or recurrent pulmonary hypertension.Riociguat is the only approved drug for CTEPH,although its effect is limited.Balloon pulmonary angioplasty(BPA)is a promising alternative treatment for patients with CTEPH.After more than 30 years of development and refinements,emerging evidence has confirmed its role in patients with inoperable CTEPH or residual/recurrent pulmonary hypertension,with acceptable complications and comparable longterm prognosis to PEA.This review summarizes the pathophysiology of CTEPH,BPA history and development,therapeutic principles,indications and contraindications,interventional procedures,imaging modalities,efficacy and prognosis,complications and management,bridging and hybrid therapies,ongoing clinical trials and future prospects.

Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension

BACKGROUND： At present, inhalation of nitrogen monoxidum （NO） or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide （BVE-CGRP） and nitricoxide synthase （NOS） in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension. OBJECTIVE： To observe the effects of stellate block on calcitonin gene-related peptide （CGRP） of vasodilation factors, prostacyclin, endothelin-i of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase （BVE-NOS） and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension. DESIGN： Randomly controlled animal study. SETTING： Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College. MATERIALS： A total of 24 adult Japanese rabbits of both genders and weighing 2.3 - 2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system （Leica-Q500IW） was made in Germany. METHODS：The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002. ① Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition, one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block group, hypoxia group and hypoxia ＋ stellate block group, with 6 in each group. Rabbits in the normal control group were perfused with saline through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total; in addition, rabbits in the stellate block group were perfused with 2.5 g/L bupivacaine through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Rabbits in the hypoxia group were used to establish hypoxic pulmonary artery hypertension models. That was to say, the experimental rabbits were put in hypoxic box （containing sodalime and calcium chloride to absorb CO2 and water） and given various flows of oxygen and nitrogen through the two lateral wells simultaneously. And then, oxygen was monitored with oxygen-concentration monitoring device to control the concentration in （10±2）% for 8 hours per day and 2 successive weeks in total. Rabbits in the hypoxia ＋ stellate block group were used to establish hypoxia models as the same as those in the hypoxia group. Two weeks later, 2.5 g,/L bupivacaine was pushed into epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Breast was directly opened to measure mean pulmonary artery pressure.② 6 mL blood was collected through pulmonary arterial duct to measure levels of plasma CGRP, prostacyclin, endothelin-I and thromboxane with radio-immunity technique; meanwhile, immunohistochemical staining was used to observe the changes of BVE-NOS content of the experimental rabbits in all groups. MAIN OUTCOME MEASURES： Changes of CGRP, prostacyclin, endothelin-1 and thromboxane and BVE-NOS. RESULTS： A total of 24 experimental rabbits were involved in the final analysis. ①As compared with those in the normal control group, hypoxic pulmonary artery hypertension of the experimental rabbits was higher in the hypoxia group and hypoxia ＋ stellate block group after hypoxia [（3.8±0.30）, （3.16±0.45）, （2.60± 0.27） kPa, P 〈 0.05, 0.01]; CGRP was lower [（68.20 ±8.78）, （108.24 ±14.35）, （130.25 ±22.70） ng/L, P 〈 0.05, 0.01]; prostacyclin was lower [（94.45± 10.68）, （98.77± 12.31）, （155.27±20.67） ng/L, P 〈 0.01]; endothelin-1 was higher [（184.7±29.66）, （115.27± 13.62）, （98.20±11.52）, ng/L, P 〈 0.05, 0.01]; thromboxan was higher [（226.27 ±30.46）, （207.67 ±27.32）, （124.25 ± 16.89） ng/L, P 〈 0.01 ]. As compared with that in hypoxia group, hypoxic pulmonary artery hypertension was decreased in hypoxia ＋ stellate block group （P 〈 0.05）, CGRP was increased （P 〈 0.01）, and endothelin-1 was decreased remarkably （P 〈 0.05）. ② Level of BVE-NOS of the experimental rabbits was higher in stellate block group, hypoxia group and hypoxia ＋ stellate block group than that in the normal control group [（0.25±0.06）, （0.27±0.07）, （0.46± 0.12）, （0.14±0.03）, P 〈 0.05], and NOS level was higher in the hypoxia ＋ stellate block group than that in hypoxia group （P 〈 0.05）. CONCLUSION： Mean arterial pressure is decreased in rabbits with hypoxic pulmonary artery hypertension after stellate block and level of endothelin-1 is also decreased; however, levels of CGRP and NOS are increased respectively.

Role of Adrenomedullin in Congenital Heart Disease Associated with Pulmonary Hypertension

The changes of adrenomedullin (ADM), endothelin-1 (ET-1) and nitric oxide (NO) levels before and after operation in congenital heart disease (CHD) associated with pulmonary hypertension (PH) were observed in order to investigate their role in CHD with PH and their clinical significance. The CHD patients were divided into 3 groups according to pulmonary artery systolic pressure (PASP): Non-PH group: PASP≤30 mmHg ( n =11); mild-PH group: PASP 31-49 mmHg ( n =10); moderate or severe-PH group: PASP≥50 mmHg ( n =12). The control group consisted of 15 health children. Plasma ADM, ET-1 and NO levels were determined by radioimmunoassay and colorimetry methods. The correlation between ADM and ET-1, NO, PASP was analyzed. The changes in plasma ADM, ET-1 and plasma NO on the 7th day after operation among the groups were compared. The results showed that plasma ADM levels in non-PH group were significantly higher than that in control group ( P <0.05), but there was no significant difference in ET-1 and NO levels between the two groups ( P >0.05). ADM and ET-1 levels in mild-PH group were significantly elevated as compared with those in non-PH group (both P <0.05), but NO levels were decreased ( P <0.05). ADM and ET-1 levels in moderate or severe-PH groups were increased as compared with those in mild-PH group (both P <0.01), but NO level significantly declined ( P <0.05). On the 7th day after operation, plasma ADM and ET-1 levels in PH group were significantly decreased ( P <0.05, P <0.01) as compared with those before operation, but there was no significant difference in NO levels ( P >0.05). But NO levels in non-PH group were significantly increased ( P <0.05). Plasma ADM levels in CHD were positively correlated with PASP and ET-1 ( r =0.77, P <0.01; r =0.82, P <0.01), negatively correlated with NO ( r =-0.56, P <0.05). It was concluded that during the progression of PH in the cases of CHD, plasma ADM, ET-1 and NO might play an important role in the development of PH. The increased ADM may represent a compensatory mechanism. It can interact with NO and ET-1 to regulate pulmonary circulation in the pathophysiology of PH with CHD. ADM may be involved in the defence mechanism against further increase of pulmonary arterial pressure. ADM could be used as a reliable indicator of the severity of CHD associated PH.

Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.