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Background: Obstructed total anomalous pulmonary venous connection (TAPVC) typically present with severe cardiovascular decompensation and requires urgent surgical management. Pulmonary arterial hypertension (PAH) is a major risk factor affecting mortality. Perioperative management focuses on providing inotropic support and managing potential pulmonary hypertensive episodes. Milrinone and inhaled nitric oxide (iNO) efficiently reduce pulmonary artery pressure (PAP) and help to improve the outcome. The aim was to determine the outcome of patients with high PAP with milrinone alone and a combination of iNO and milrinone. Material and Method: After ethical committee approval, the study was conducted over a period of 3 years in 80 patients with obstructed TAPVC repair. A total of 80 patients having severe PAH (supra systemic arterial pressure) randomly divided into two groups with 40 patients in each (M & MN). Group M (milrinone) patients received milrinone and Group MN (milrinone & iNO) patients received both milrinone (after opening aortic cross clamp) and iNO (post operative ICU). Ventilation time, hospital stay, ICU stay, complications, in hospital mortality were compared between both groups. Result: Ventilation time, Intensive Care Unit (ICU) stay, hospital stay for group M was 8.02 � 5.74 days, 11.25 � 7.33 day, 14.92 � 8.55 days, respectively, and for group MN was 5.02 � 1.78 days, 8.27 � 3.24 days, 10.3 � 3.18 days, respectively. In hospital mortality for group M and MN was 10% and 2.5%, respectively. P value for each variable was significant < 0.05 (except mortality). Conclusion: Most of the patients with obstructed TAPVC had severe PAH. Management of severe PAH with a combination of milrinone with iNO had a better outcome than milrinone alone.
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The heavily harsh plateau environment including low pressure, hypoxia, cold, dryness and strong ultraviolet radiation, seriously threatens the physical and mental health of those who quickly enter the plateau area. Lungs are the sensitive organs for high altitude injury. High-altitude lung diseases include the acute high-altitude lung disease (i.e., high-altitude pulmonary edema), the chronic high-altitude lung disease (i.e., high-altitude pulmonary artery hypertension) and the high-altitude de-adapted reaction. This review summarizes the pathogenic mechanisms and the main therapeutic drugs of high-altitude lung diseases based on the recent research. Moreover, the related formulations and administration routes are also reviewed here. It will provide support and counsel for the diagnosis and treatment of high-altitude lung diseases.
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Heart transplantation can save the life and improve the quality of life of patients with end-stage heart failure. Nevertheless, it is not suitable for all patients with end-stage heart failure. As a common complication of end-stage heart failure, pulmonary artery hypertension may increase the incidence of right heart failure after heart transplantation, which is associated with the short- and long-term fatality risk in the recipients after heart transplantation. In clinical practice, different transplant centers have different criteria for heart transplantation indications in patients with end-stage heart failure complicated with pulmonary artery hypertension. Accurate preoperative evaluation of surgical indications plays a critical role in determining the success of heart transplantation. In this article, the definition, pathogenesis and effects on heart transplantation, diagnostic methods and reversibility judgment of pulmonary artery hypertension, diagnostic treatment of reversible pulmonary artery hypertension and indications of heart transplantation in patients with end-stage heart failure complicated with reversible pulmonary hypertension were reviewed.
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Objective To evaluate the surgical treatment for congenital heart disease plus pulmonary artery hypertension (CHD-PAH) in children weighing less than 5 kg. Methods The clinical data of 29 CHD-PAH children with body weight ≤5 kg who were treated surgically between Aug. 2016 and Aug. 2018 were collected and retrospectively analyzed. Surgical complications and death causes were analyzed. Pulmonary artery pressure (PAP), the ratio of main pulmonary artery to ascending aorta diameter (MPA/AAO), the ratio of ventricular pre-ejection period to acceleration time (PEP/AT), arterial oxygen partial pressure (PaO2), pulse oxygen saturation (SpO2), the ratio of height to normal children, the ratio of weight to normal children, and functional classification of pulmonary arterial hypertension were evaluated in 26 survival children before surgery, before discharge and at 6 months after surgery. Results The procedures were finished successfully in all the 29 children. Postoperative complications were as follows: Low cardiac output syndrome (LCOS, 2 cases), pulmonary hypertension crisis (1 case), residual shunt or recanalization (2 cases), arrhythmia (1 case), hepatic insufficiency (1 case), and delayed wound healing (2 cases). Three children (10.3%) died; of them 2 died of LCOS and one died of pulmonary hypertensive crisis. The above-mentioned indexes were significantly improved before discharge and at 6 months after surgery (P<0.05). The growth and development of 24 children reached the normal level 6 months after surgery. Conclusion Surgical treatment is safe and effective for CHD-PAH children with body weight≤5 kg, which can restore normal growth and development of the children.
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Objective To explore the role of iTr35 cells in the pathogenesis of children with pulmonary artery hypertension(PAH)in children,and the percentage of iTr35 cells and serum interleukin(IL)_35 levels in peripheral blood of patients with PAH were investigated. Their inhibitory effects on the expression of vascular cell adhesion mole_cule_1(VCAm_1)on vascular endothelial cells were also analyzed. Methods After 3 mL peripheral blood of 30 congenital heart disease( CHD)patients with PAH,22 CHD patients without PAH and 30 age or gender matched healthy controls(HC)were collected,the percentage of iTr35 cells were detected by flow cytometry and the concentra_tions of serum IL_35 were detected by Luminex,as well as soluble VCAm_1(sVCAm_1). Human pulmonary artery endothelial cells(HPAECs)were cultured in υitro and divided into control group,tumor necrosis factor( TNF)_α group and IL_35+TNF_α group. The expression of VCAm_1 and nuclear factor( NF)_κB P65 protein of each group were detected by flow cytometry and Western blot. The adhesion of peripheral blood mononuclear cells(PBmCs) to HPAECs was observed by fluorescence microscope. Results Compared to CHD patients without PAH,the percent_age of iTr35 cells[0. 86(0. 45_1. 63)% υs. 1. 14(0. 46_2. 11)%](H=20. 52,P<0. 05)in peripheral blood and serum IL_35 levels[2. 43(1. 76_2. 85)μg/L υs. 3. 17(2. 92_5. 66)μg/L]( H=119. 56,P<0. 05)were signifi_cantly decreased in CHD patients with PAH. However,serum sVCAm_1 concentration[923. 1(892. 6_1 118. 7)μg/L υs. 776. 1(743. 5_932. 3)μg/L ]in CHD patients with PAH were significant increased( H=65. 65,P<0. 05). In addition,the concentration of serum IL_35 were negatively correlated with sVCAm_1 in PAH patients(r= _0. 374 P=0. 042). In υitro,the positive rate of VCAm_1 on HPAECs was significant decreased in IL_35+TNF_α group as compared to the TNF_α group[(2. 07 ± 0. 82)% υs.(5. 83 ± 1. 34)%,F=1 197. 18,P<0. 05]. In addition,the protein expression of NF_κB P65 in HPAECs was significantly decreased in TNF_α+IL_35 group as compared to TNF_α group,as well as the adhesion of PBmCs to HPAECs(F=212. 04,2 533. 51,all P<0. 05). Conclusions The percentages of iTr35 and levels of IL_35 are reduced in the peripheral blood of patients with PAH. Through in υitro ex_periments,IL_35 is found to reduce PBmCs adhesion by inhibiting VCAm_1 expression in HPAECs.
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Objective@#To explore the role of iTr35 cells in the pathogenesis of children with pulmonary artery hypertension (PAH) in children, and the percentage of iTr35 cells and serum interleukin(IL)-35 levels in peripheral blood of patients with PAH were investigated.Their inhibitory effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells were also analyzed.@*Methods@#After 3 mL peripheral blood of 30 congenital heart disease (CHD) patients with PAH, 22 CHD patients without PAH and 30 age or gender matched healthy controls (HC) were collected, the percentage of iTr35 cells were detected by flow cytometry and the concentrations of serum IL-35 were detected by Luminex, as well as soluble VCAM-1 (sVCAM-1). Human pulmonary artery endothelial cells (HPAECs) were cultured in vitro and divided into control group, tumor necrosis factor (TNF)-α group and IL-35+ TNF-α group.The expression of VCAM-1 and nuclear factor(NF)-κB P65 protein of each group were detected by flow cytometry and Western blot.The adhesion of peripheral blood mononuclear cells (PBMCs) to HPAECs was observed by fluorescence microscope.@*Results@#Compared to CHD patients without PAH, the percentage of iTr35 cells[0.86(0.45-1.63)% vs.1.14(0.46-2.11)%](H=20.52, P<0.05) in peripheral blood and serum IL-35 levels[2.43(1.76-2.85) μg/L vs.3.17(2.92-5.66) μg/L](H=119.56, P<0.05) were significantly decreased in CHD patients with PAH.However, serum sVCAM-1 concentration[923.1(892.6-1 118.7) μg/L vs.776.1(743.5-932.3) μg/L ] in CHD patients with PAH were significant increased (H=65.65, P<0.05). In addition, the concentration of serum IL-35 were negatively correlated with sVCAM-1 in PAH patients (r=-0.374 P=0.042). In vitro, the positive rate of VCAM-1 on HPAECs was significant decreased in IL-35+ TNF-α group as compared to the TNF-α group [(2.07±0.82)% vs.(5.83±1.34)%, F=1 197.18, P<0.05]. In addition, the protein expression of NF-κB P65 in HPAECs was significantly decreased in TNF-α+ IL-35 group as compared to TNF-α group, as well as the adhesion of PBMCs to HPAECs (F=212.04, 2 533.51, all P<0.05).@*Conclusions@#The percentages of iTr35 and levels of IL-35 are reduced in the peripheral blood of patients with PAH.Through in vitro experiments, IL-35 is found to reduce PBMCs adhesion by inhibiting VCAM-1 expression in HPAECs.
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@#Objective To explore the treatment method of congenital heart disease (CHD) with pulmonary artery hypertension (PAH) in infants with Down syndrome (DS). Methods The clinical data of 60 CHD patients with PAH from March 2015 to August 2016 in our hospital were retrospectively analyzed. There were 30 infants with DS classified as a DS group (trial group, 17 males and 13 females with a mean age of 1.15±0.25 years) and the other 30 patients without DS were classified as a control group (20 males and 10 females with a mean age of 1.24±0.30 years). All the patients underwent surgical treatment and fasudil combined with sildenafil were used to prevent pulmonary hypertension crisis postoperatively. Results There was no significant difference in cardiopulmonary bypass time, aortic cross-clamping time, modified ultrafiltration time and the incidence of postoperative respiratory complications between the two groups. The pulmonary systolic blood pressure significantly decreased at 24 h after operation in the two groups (both P<0.05). The arterial oxygen pressure and oxygenation index of the trial group were lower than those of the control group at 6 h after operation (both P<0.05). The mechanical ventilation time and intensive care time of the trial group were significantly longer than those of the control group (P=0.007 and P=0.000, respectively). There were no reoperations or early death. Conclusion The effects of surgical repair of CHD with PAH in infants with DS are satisfactory by grasping the indication, protecting lung function and controlling PAH in the early postoperative period, although there is a high incidence of pulmonary complications.
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Background: Pulmonary artery hypertension (PAH) is the most common cause of right heart failure and right ventricular dysfunction(RVD). Portopulmoanry hypertension (POPH) is a form of pulmonary arterial hypertension (PAH) associated with portal hypertension with or without underlying chronic liver disease leading to right venricular dysfunction. The aim of this study is to evaluate prevalence of right ventricular dysfunction and its association with pulmonary artery hypertension, body mass index(BMI), systemic hypertension and smoking. Material and methods: This is a cross-sectional observation study, it was conducted on 84 patients with portal hypertension. Trans-thoracic echocardiography was done for calculation of PASP (pulmonary artery systolic pressure) and TAPSE(tricuspid annulus plane systolic excursion), TDI( tissue doppler imaging) S’ for RVD. Observation: Prevalence of RVD was was 14.28%%, in male it was 15.6% and female it was 20.0%. Sex was insignificant in RVD with p value of 0.74. Mean age of POPH patients were 53.33+ 8.3 year, age was insignificant with p-value 0.86. BMI,hypertension and PAH was found significant in RVD patients with p- value of 0.01, 0.008 and 0.0001 respectively. Smoking was insignificant (P-0.971). Conclusion:There is association of right ventricular dysfunction with pulmonary hypertension in portal hypertensive patients.
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OBJECTIVE@#To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension.@*METHODS@#Forty SD rats were random-ly divided into four groups:normoxic control group (N), hypoxia hypercapnia group (HH), ERS inhibitor 4-phenylbutyric acid group (4-PBA), endoplasmic reticulum stress (ERS) pathway agonist tunicamycin group (TM), ten rats in each group.The mean pulmona-ry artery pressure (mPAP), mean carotid artery pressure (mCAP) and right ventricular hypertrophy index of rats in each group were measured.Pulmonary artery smooth muscle cells were identified by immunofluorescence α-smooth muscle actin (α-SMA).Morphologi-cal changes of lung tissue and pulmonary artery were observed by electron microscope.The apoptotic index of pulmonary artery smooth muscle cells in each group was detected by TUNEL.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and cysteinyl aspartate specific proteinase-12 (caspase-12) mRNA and protein in each group.@*RESULTS@#①Compared with the N group, the mPAP, the ratio of right ventricle weight to left ventricle plus ventricular septum weight[RV/(LV+S)]and the ratio of pulmonary artery wall area to total tube area (WA/TA) were increased (<0.01), and the ratio of pulmonary artery luminal area to total tube area (LA/TA) were decreased (<0.01), pulmonary artery smooth muscle cell apoptosis index were decreased (<0.05 or <0.01) in HH group, 4-PBA group and TM group.ERS related protein and mRNA expressions were increased, the differences were statistically significant.②Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of 4-PBA group were decreased ( <0.01), LA/TA and pulmonary artery smooth muscle cell apoptosis index were increased (<0.01, <0.05).The expressions of ERS related protein and mRNA were all decreased (<0.05 or <0.01).③Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of TM group were increased (<0.05 or <0.01), pulmonary artery middle layer thickened, LA/TA and pulmonary artery smooth muscle cell apoptotic index were decreased (<0.01).ERS related protein and mRNA expressions were increased with statistical significance except GRP78 protein.@*CONCLUSIONS@#Pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia may be related to the excessive proliferation of pulmonary artery smooth muscle cells and too little apopto-sis;ERS related factors (JNK, caspase-12 and CHOP) are involved in the regulation of pulmonary hypertension induced by hypoxia hypercapnia.
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Animals , Rats , Endoplasmic Reticulum Stress , Hypercapnia , Hypertension, Pulmonary , Hypoxia , Pulmonary Artery , Rats, Sprague-DawleyABSTRACT
OBJECTIVE Salvianolic acid A (SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge)and exhibits many pharmaco-logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. However, whether SAA improves vascular remodeling induced by pulmonary arterial hypertension (PAH) remains unknown. In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg·kg-1).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive con-trol Bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab-normalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in-jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge-netic protein typeⅡ receptor (BMPRⅡ) and phosphorylated Smad1/5 in the lungs. CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa-tients at high risk of PAH.
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Pulmonary hypertension is characterized by the progressive increase of pulmonary arterial pressure and the gradually increasing of pulmonary vascular resistance,leading to a common disease of right heart failure and death.The pathogenesis of pulmonary hypertension has not yet been fully elucidated.The pathological feature of pulmonary arterial hypertension is the pulmonary vascular remodeling including vascular endothelial cell injury,smooth muscle cell proliferation,migration and deposition of extracellular matrix.MicroRNA is an endogenous nucleotide fragment,which can activate the expression of genes related to signal transduction through the corresponding biological behavior.Recent studies have found that microRNA plays an important role in pulmonary arterial hypertension through the injury of vascular endothelial cells,smooth muscle cell proliferation,migration and extracellular matrixdeposition.The research about microRNA that participates in the mechanism of pulmonary arterial hypertension provides a new theoretical basis for the prevention and treatment of pulmonary arterial hypertension.This review focuses on progress of microRNA and the mechanisms of pulmonary arterial hypertension.
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Pulmonary artery hypertension is a disease with complicated pathogenesis, which is characterized by enhanced pulmonary artery constriction and arterial wall remodeling, leading to progressive increase of pulmonary vascular resistance and pulmonary artery pressure, then resulting in right heart failure.Many studies have shown that transforming growth factor-β1(TGF-β1) plays an important role in the development of various diseases, especially in cardiovascular and cerebrovascular diseases.TGF-β1 is involved in multiple cellular responses including cell proliferation, differentiation, migration and apoptosis.TGF-β1 participates in pulmonary artery hypertension mainly via promoting the proliferation of pulmonary artery smooth muscle cells as well as inducing the deposition of extracellular matrix and endothelial-to-mesenchymal transition(EndMT) through many signaling, which is mainly dominated by pulmonary artery smooth muscle cells and pulmonary artery endothelial cells.This review mainly introduces the role of TGF-β1 in pulmonary artery hypertension in order to provide potential drug targets and therapeutic strategies for pulmonary artery hypertension.
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Objective To analyze preoperative risk factors of perioperative pulmonary hypertension crisis (PHC) for pregnant woman with severe pulmonary artery hypertension (PAH), and approach its clinical value. Methods A retrospective analysis was conducted. The clinical data from 152 pregnant women with severe PAH underwent cesarean delivery admitted to Beijing Anzhen Hospital from January 1st 2008 to December 31st 2016 was collected. The patients were divided into two groups according to with perioperative PHC or not. Through the case management system, age, height, weight, gestational age, pregnancy time, type of PAH, emergency or selective surgery, New York Heart Association (NYHA) cardiac function classification, and preoperative ultrasound left ventricular ejection fraction (LVEF), left ventricular diastolic final diameter (LVEDD), the pulmonary artery systolic pressure (sPAP) estimated by ultrasonic TI method, radial artery systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO2) without oxygen, oral sildenafil ingestion, having Swan-Ganz catheter placement or not, and whether used norepinephrine or not, as well as the occurrence of perioperative PHC and clinical outcomes were collected. Possible preoperative risk factors were compared between the two groups by single factor and multiple factors logistic regression analysis. The receiver-operating characteristic curve (ROC) was plotted to assess the diagnostic value of various risk factors.Results A total of 152 patients were screened. Ten patients got heart surgery under general anesthesia at the same time, and 4 patients experiencing cesarean section with general anesthesia were excluded. 138 patients were enrolled finally, 27 patients underwent perioperative PHC (19.57%), and 17 patients died with a mortality of 62.96%. Compared with non-PHC group, the patients in PHC group were older (years: 25.07±3.55 vs. 27.64±4.82), had a poor cardiac function (NYHA cardiac function classification: 3.22±0.64 vs. 2.85±0.53), a smaller LVEDD (mm: 38.78±4.76 vs. 43.91±9.67), lower SpO2 without oxygen (0.83±0.12 vs. 0.92±0.06) and oral sildenafil ingestion rate (29.63% vs. 56.76%), and higher sPAP estimated by ultrasonic TI method [mmHg (1 mmHg = 0.133 kPa): 113.41±24.73 vs. 99.35±21.10] and DBP (mmHg: 79.63±13.23 vs. 75.23±12.14), more having Swan-Ganz catheter placement (85.19% vs. 57.66%), more Eisenmenger syndrome (70.37% vs. 37.84%), and more emergency operation (48.15% vs. 23.42%, allP ≤ 0.1). The variables with statistically significant differences showed by single factor analysis were collected, and it was shown by multiple factors logistic regression analysis that LVEDD [odds ratio (OR) = 0.878, 95% confidence interval (95%CI) = 0.796-0.968,P = 0.009], whether oral taken sildenafil (OR = 0.161, 95%CI = 0.051-0.515,P = 0.002) or not, SpO2 at room air (OR = 0.882, 95%CI = 0.829-0.938,P = 0.000), Swan-Ganz catheter placement or not (OR = 6.186, 95%CI = 1.533-24.964,P = 0.010) were independent risk factors of perioperative PHC in pregnant women with severe PAH. It was shown by ROC curve analysis that the area under the ROC curve (AUC) of four factors mentioned above combined diagnosis for PHC was 0.878 (P = 0.000) with the sensitivity of 88.89% and specificity of 76.58%.Conclusions PHC is very dangerous for gravida with severe PAH, and the mortality rate is very high. LVEDD, oral sildenafil, SpO2 at room air, Swan-Ganz catheter placement or not were independent risk factors of perioperative PHC for severe PAH maternal. Four preoperative factors of perioperative PHC joint diagnosis accuracy were higher.
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Aim To investigate the relationship between monocyte chemoattractant protein-1(MCP-1) and pulmonary artery hypertension after acute pulmonary thromboembolism(PTE), and to explore the effects and mechanisms of resveratrol with MCP-1 in the acute PTE as well.Methods The acute PTE model of Sprague-Dawley rats was replicated using self-thrombosis.The rats were randomly divided into five groups(Normal, Solvent, acute PTE, antibody Cl142, and resveratrol), and 1h, 4h, 8h and 3 points were observed in each group.A model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter.Resveratrol or Cl142, dissolved in 1％ dimethyl sulfoxide(DMSO), was administered to the animals through caudalvein 1 h prior to the beginning of acute PTE modeling.Rats in normal control group and solvent control group were injected with normal saline and 1％ DMSO respectively.The mean pulmonary artery pressure(MPAP) and the mRNA and protein expression of MCP-1 were measured at each time point.Results ① The acute PTE group MPAP, MCP-1 mRNA and protein expression were significantly higher than those of the control group(P<0.05) at the same time;② The resveratrol group′s MPAP and MCP-1 mRNA, protein expression were significantly lower than those of the acute PTE group(P<0.05) at the same time;③ The Cl142 group MPAP and MCP-1 mRNA, protein expression were markedly reduced in the acute PTE group(P<0.05) at the same time.Conclusions The large expression of MCP-1 after acute PTE is involved in the formation of pulmonary hypertension after acute PTE.Resveratrol can reduce the pressure of pulmonary artery after acute PTE by down-regulating the MCP-1 expression.
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Objective The aim of this study was to establish a rat models of pulmonary artery hypertention with monocrotaline, and to study the relationship between the evolution of right ventricular function and the evolution of pulmo-nary artery pressure ( PAP) by magnetic resonance ( MR) imaging of the right ventricular function. Methods Rat models of pulmonary artery hypertension were established by monocrotaline (MCT). The model rats were divided into 4 groups:the 1-week-PAH group, 2-week-PAH group, 3-week-PAH group, and 4-week-PAH group, and pulmonary artery pressure in the rats was measured by right heart catheterization. After injection of MCT, we used MRI to evaluate the ventricular function of the rats every week. All the measurement data of right ventricular function in the model group were compared with the average pulmonary pressure using Pearson' s correlation test. Results There were strong correlations between the parameters of RV function in model group with the average pulmonary pressure ( r= -0. 823 for RV EF, r=0. 732 and 0. 803 for RV EDV and RV ESV) . At 2 weeks after injection of monocrotaline, the mean pulmonary pressure, right ven-tricular eject fraction ( RVEF) , the end-diastolic volume ( EDV) and the end-systolic volume ( ESV) of right ventricle be-tween rats in PAH and the control group showed no significant difference (P>0. 05). But three-four weeks after MCT in-jection, all these parameters were significantly different in the PAH rats than in control rats (P<0. 05). Conclusions As the pulmonary arterial pressure is increased in the rats, the right ventricular function is gradually impaired. For the monito-ring of chronic pulmonary artery hypertension in rats, MRI can be used to accurately measure the changes of parameters. The PAH can be indicated by looking at the changes of parameter such as RV EF, RV EDV and RV ESV.
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Objective The aim of this study was to establish a rat models of pulmonary artery hypertention with monocrotaline, and to study the relationship between the evolution of right ventricular function and the evolution of pulmo-nary artery pressure ( PAP) by magnetic resonance ( MR) imaging of the right ventricular function. Methods Rat models of pulmonary artery hypertension were established by monocrotaline (MCT). The model rats were divided into 4 groups:the 1-week-PAH group, 2-week-PAH group, 3-week-PAH group, and 4-week-PAH group, and pulmonary artery pressure in the rats was measured by right heart catheterization. After injection of MCT, we used MRI to evaluate the ventricular function of the rats every week. All the measurement data of right ventricular function in the model group were compared with the average pulmonary pressure using Pearson' s correlation test. Results There were strong correlations between the parameters of RV function in model group with the average pulmonary pressure ( r= -0. 823 for RV EF, r=0. 732 and 0. 803 for RV EDV and RV ESV) . At 2 weeks after injection of monocrotaline, the mean pulmonary pressure, right ven-tricular eject fraction ( RVEF) , the end-diastolic volume ( EDV) and the end-systolic volume ( ESV) of right ventricle be-tween rats in PAH and the control group showed no significant difference (P>0. 05). But three-four weeks after MCT in-jection, all these parameters were significantly different in the PAH rats than in control rats (P<0. 05). Conclusions As the pulmonary arterial pressure is increased in the rats, the right ventricular function is gradually impaired. For the monito-ring of chronic pulmonary artery hypertension in rats, MRI can be used to accurately measure the changes of parameters. The PAH can be indicated by looking at the changes of parameter such as RV EF, RV EDV and RV ESV.
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Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration. However, many of the currently available anti-PAH drugs suffer from a number of limitations, including short biological half-life, and poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with selectivity toward pulmonary circulation when it is administered via the pulmonary route. However, PGE1 has a very short half-life of 5–10 minutes. Therefore, we hypothesized that long-term effect of PGE1 could reduce mal-adaptive structural remodeling of the lung and heart and prevent ventricular arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and endothelin receptor A, and the expression of fibrosis. These results support the notion that PGE1 can improve the functional properties of RV, highlighting its potential benefits for heart and lung impairment.
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Animals , Rats , Alprostadil , Arrhythmias, Cardiac , Arterial Pressure , Arterioles , Disease Progression , Endothelin-1 , Fibrosis , Half-Life , Heart , Heart Ventricles , Hypertension , Hypertrophy , Lung , Models, Animal , Muscle, Smooth , Pulmonary Artery , Pulmonary Circulation , Receptors, Endothelin , Vascular Diseases , Vascular ResistanceABSTRACT
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment.
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Animals , Rats , Arrhythmias, Cardiac , Arterial Pressure , Death , Disease Progression , Fibrosis , Heart , Heart Ventricles , Hypertension , Hypertrophy , Models, Animal , Myocytes, Cardiac , Natriuretic Peptide, Brain , Pulmonary Artery , Sodium , Vascular Diseases , RanolazineABSTRACT
Objective To study pulmonary wedge angiography ( PWA ) with hemodynamic the evaluation of children with congenital heart disease and pulmonary artery hypertension ( PAH) . Methods Hemodynamic measurement and pulmonary wedge angiography were performed in 50 children with congenital heart disease. Comparison and analysis were made from the data obtained from PWA and catheterization. Results After PWA, the patients were categorized into 3 groups according to the measured hemodynamics parameters:group A [ n=15, patients with normal mean pulmonary artery pressure ( mPAP≤25 mmHg) and normal pulmonary vessel resistance (PVR﹤300 dyne?s?cm5)], group B [n=24, patients with PAH (mPAP﹥25 mmHg) but normal PVR] and group C (n=11, patients with PAH and elevated PVR (PVR≥300 dyne?s?cm5). Rote of tapering (ROT) was significant lower in group C than in group A and B (F=42. 559,P﹤0. 05). Pulmonary circulation time (PCT) was higher in group C than in group A and B (F=6. 037,P﹤0. 05). ROT correlated negatively with PVR (r = -0. 606, P ﹤0. 05). PCT index correlated positively with PVR (r=0. 783,P=0. 01). There was no significant correlation between PCT and mean pulmonary artery hypertension (mPAP). Conclusions PWA may help to make quantitative analysis of the pulmonary vascular status in patients with congenital heart disease.
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Objective To investigate the significance of peroxisome proliferator-activated receptor (PPAR)γexpression in the lung tissue of rats with chronic hypoxic pulmonary hypertension (HPAH). Methods Forty male Sprague-Dawley rats were randomly divided into four groups (n=10 for each group):normal control group (NC), hypoxia control group-one-week (HC-1w), hypoxia control group-two-week (HC-2w) and hypoxia control group-three-week (HC-3w). Normal control group was raised under normal oxygen condition in ventilated animal cage for three weeks. The other HC groups were placed in a low oxygen chamber (O2 concentration of 10%) from 9:00 AM-5:00 PM (8 h/d) everyday by one week, two weeks and three weeks. The mean pulmonary arterial pressure (mPAP), right ventricular systolic pressure (RVSP) were detected. The index of right ventricular hypertrophy RV/(LV+S) was measured by dissecting rat heart. The morphological changes of the small pul-monary arteries were observed by HE staining, and the percentage of vascular wall thickness (WT%) was calculated. The ex-pression level of PPARγprotein was detected by Westren blot assay. Results The mPAP, RVSP and RV/(LV+S) were sig-nificantly higher in HC groups than those of NC group (P<0.05). The morphology of pulmonary arteries showed vessel wall thickening and vessel lumina stenosis in HC groups compared with that of NC group. The PPARγexpression in lung tissue was significantly lower in HC groups than that of NC group, and the downward trend was more obvious with the extension of time. Conclusion PPARγplays an important role in the occurrence and development of chronic hypoxic pulmonary hyper-tension.