“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.

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.

Compression of Left Main Coronary Artery in Patients with Pulmonary Artery Aneurysm and Pulmonary Hypertension

Background: Pulmonary artery aneurysm (PAA) is an unusual finding and its association with left main coronary (LMCA) compression is even more infrequent. Cardiac CT evaluates of presence and size of PAA and the degree of LMCA compression. The aim of this study is to describe two cases of adults with compression of LMCA with PAA associated with PDA and pulmonary hypertension. Case presentation: The first case is a 27-year-old man with PAA (78 mm diameter) and LMCA compression of 70% between the aortic sinus and the PAA. He presented angina as a manifestation of the LMCA compression. During follow-up the patient died. The second case is a 28-year-old man with PAA (110 mm diameter) that compresses LMCA in 55%, he rejected surgical treatment, but he is in close follow-up with medical treatment. Conclusion: Cardiac computed tomography played an important role both in the diagnosis and identification of high-risk PAA patients.

Early Results of Mitral Valve Replacement in Severe Pulmonary Artery Hypertension—An Institutional Prospective Study

Introduction: In patients undergoing surgery for mitral valve replacement (MVR) for valvular heart disease, pulmonary artery hypertension (PAH) has been considered a major risk factor. In this prospective study, we have studied the early hemodynamic changes and post-operative outcomes of MVR among patients with severe PAH. Methods: 68 consecutive patients who underwent mitral valve replacement for severe rheumatic mitral valve disease with severe PAH (pulmonary artery pressure (PAP) > 50 mmHg) were studied prospectively for immediate postoperative hemodynamics and outcomes. The mean age of the patients was 32.1 years. 32 (47.05%) patients had mitral stenosis, 13 (19.11%) had mitral regurgitation and 23 (33.82%) had mixed lesions. Patients were divided into two groups based on preoperative pulmonary artery pressures. In 56 patients (82.35%, group I) PAP was sub-systemic or systemic, with a mean of 58.4 mmHg. Twelve patients (17.65%, group II) had supra-systemic PAP with a mean of 82.4 mmHg. Results: After mitral valve replacement, the PAP and pulmonary vascular resistance (PVR) decreased significantly in group I to near normal levels. In group II also the PAP and PVR decreased significantly but significant residual PAH remained. Operative mortality was 3.5% in group I and 16.6% in group II. Conclusions: MVR is safe and effective at the presence of severe PAH as long as the PAP is below or equal to systemic pressures. With suprasystemic PAP, MVR carries a high risk of mortality and the patient continues to have severe PAH in the postoperative period.

Chronic thromboembolic pulmonary hypertension(CTEPH):outcomes of surgical effect in patients with unilateral main pulmonary artery occlusion

Objective To summarize the clinical characteristics and the effect of pulmonary endarterectomy(PEA)in CTEPH patients with unilateral main pulmonary artery occlusion.Methods Of 160 CTEPH patients operated between January2004 and March 2018 at our center,13(8.1%)had complete main pulmonary artery occlusion.Patients were included if the ventilation/perfusion(V/Q)scan revealed nonperfusion of an entire lung and the pathological examination showed chronic thromboembolic.

Role of Na^+/H^+ antiporter in pulmonary artery smooth muscle of hypoxic pulmonary hypertension in the rat

Objective: To investigate the role of Na+ /H+ antiporter in the hypoxic pumonary hypertension ofrats. Methods: Thirty Wistar rats were randomly divided into 3 groups with 10 in each group: controlgroup, 3--week hypoxia group and 8--week hypoxia group. After the isolation of pulmonary artery smoothmuscles, pHi was determined by fluorescence measurement of the pH--sensitive dye BCECF and theexpression of NHE--1 mRNA was detected with reverse transcription--polymerase chain reaction. Results: ThepHi and expression of NHE-1 mRNA of pulmonary artery smooth muscle cell in the hypoxia groups weresignificantly increased than those in the normal group (P < 0. 01 ). There was no remarkable differencebetween the hypoxia groups. Conclusion: With the function of regulation pHi., NHE--1 may play an importantrole in the pulmonary vascular remodeling of pulmonary hypertension. The result provides a new therapeuticmethod with NHE--1 inhibitors and/or gene therapy for the hypoxic pulmonary hypertension.

Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:Current guidelines for managing pulmonary arterial hypertension(PAH)recommend a risk strati-fication approach.However,the applicability and accuracy of these strategies for PAH associated with congenital heart disease(PAH-CHD)require further validation.This study aims to validate the reliability and predictive accuracy of a simplified stratification strategy for PAH-CHD patients over a three-year follow-up.Additionally,new prognostic variables are identified and novel risk stratification methods are developed for assessing and managing PAH-CHD patients.Methods:This retrospective study included 126 PAH-CHD patients.Clinical and biochemical variables across risk groups were assessed using Kruskal-Wallis and Fisher’s exact tests.Indepen-dent risk factors were identified using ordered logistic regression,while Kaplan-Meier and Cox proportional hazards regression analyses evaluated their impact on all-cause mortality.A new stratification model for the PAH-CHD population was constructed based on these analyses.Results:Significant survival differences across stratified risk groups were observed(p<0.001),validating the effectiveness of the simplified risk stratification method in PAH-CHD patients.Prothrombin activity was a strong independent predictor of adverse outcomes of PAH-CHD patients(Hazard ratio 0.95,p<0.001,C-index 0.70).A model combining N-terminal pro-brain natriuretic peptide,prothrombin activity,albumin,and right atrial area achieved an area under the curve of 0.89 and a C-index of 0.85.Conclusions:The simplified risk stratification method is applicable to PAH-CHD patients.Prothrombin activity is a strong independent predictor of adverse outcomes.A comprehensive risk stratification approach,incorporating both established and novel biomarkers,enhances accessibility and offers predictive efficacy during follow-up for PAH-CHD patients,comparable to established models.

THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Plasma endothelin-1 and nitric oxide correlate with ligustrazine alleviation of pulmonary artery hypertension in patients of chronic cor pulmonale from high altitude plateau during acute exacerbation

Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

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.

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

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.

THE ALTERATION OF THE PULMONARY ARTERY FLOW SPECTRUM WITH PULMONARY HYPERTENSION

INTRODUCTION Pulmonaryhypertensionisacommoncomplicationinpatientwithcongenitalheartdisease.Thedegreeofthepulmonaryhypertensionisanimportantfactortodetermineinselectionoftreatmentscheme(1,2)andindicatestheprognosis(3).Thepurposeofthisstudywastoinve...

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.

Determination of the degree of pulmonary arteryhypertension by plasma atrial nateiuretic peptide levelsand pulmonary perfusion imaging

To evaluate the degree of pulmonary artery hypertension (PAH) and its significance, pulmonary perfusion tomographic imaging (PPTI) and radioimmunoassay of plasma atrial nateiuretic peptide (ANP) levels were examined in different stages of rabbit PAH models, controlled with cardiac catheterization. When the PAH was mild, ANP levels were not significantly changed (t= 1, p >0.05). The mean pulmonary artery pressures (mPAP) measured by catheterization had no significant change, but there was a significant increase of the ratio of dorsal/abdominal counts using pulmonary perfusion tomographic imaging (PPTI) (t=2.5, p <0.05). The ANP levels rose when PAH was moderate or severe, and the difference was significant compared with the control group (t=4 and 6.5, p <0.05). The other two methods also showed significant changes (p <0.01). There was positive correlation between the results of ANP/PPTI, ANP/catheterization, and PPTI/catheterizations (p <0.01). These results suggest that ANP levels can assess the degree of the PAH as a simple method, but it is not as sensitive as that of the PPTI in mild PAH.

Pulmonary arterial hypertension confirmed by right heart catheterization following COVID-19 pneumonia: A case report and review of literature

BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.

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.

NR4A1 enhances glycolysis in hypoxia-exposed pulmonary artery smooth muscle cells by upregulating HIF-1αexpression

Background:Pulmonary arterial hypertension(PAH)is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism.Alterations in nuclear receptor subfamily 4 group A member 1(NR4A1)activity alter the outcome of PAH.This study aimed to investigate the effects of NR4A1 on glycolysis in PAH and its underlying mechanisms.Methods:This study included twenty healthy volunteers and twenty-three PAH patients,and plasma samples were collected from the participants.To mimic the conditions of PAH in vitro,a hypoxia-induced model of pulmonary artery smooth muscle cell(PASMC)model was established.The proliferation of PASMCs was assessed using CCK8 assays.Results:Levels of NR4A1,hypoxia-inducible factor-1α(HIF-1α),and various glycolysis-related enzymes were measured.In addition,extracellular glucose and lactate production were assessed.The interaction between NR4A1 and HIF-1αwas evaluated by co-immunoprecipitation assays.Levels of NR4A1 and HIF-1αwas increased in PAH patients,and exposure to hypoxia resulted in increased levels of NR4A1 and HIF-1αin PASMCs.NR4A1 interacted with HIF-1α.NR4A1 overexpression enhanced hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,decreased glucose levels,increased lactate levels and promoted hypoxic PASMC viability.Conversely,silencing NR4A1 decreased hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,promoted glucose production,reduced lactate levels and inhibited hypoxic PASMC viability.Furthermore,overexpression of HIF-1αreversed the regulation of glycolysis caused by NR4A1 knockdown.Conclusion:NR4A1 enhances glycolysis in hypoxia-induced PASMCs by upregulating HIF-1α.Our findings indicate that the management of NR4A1 activity may be a promising strategy for PAH therapy.