Objective: To explore the association between serum levels of osteopontin (OPN) and systolic pulmonary artery pressure (sPAP) in healthy men following acute high altitude exposure. Methods: According to the inclusion and exclusion criteria, this observational study included 94 male subjects (aged from 18 to 30 years, dwelling in lowland<500 m) who ascended to Litang (4 100 m) from Chongqing (400 m) by bus with a stair-like journey within 7 days in June 2013. Data including basic information, OPN, superoxide dismutase (SOD), and malondialdehyde (MDA) and echocardiographic derived sPAP were collected within 48 hours before ascent and within 2-7 hours after arrival. Accordingly, subjects were divided into 3 groups based on the tertiles of sPAP after acute high altitude exposure: low sPAP group (26.8-32.3 mmHg (1 mmHg=0.133 kPa)) (n=31), middle sPAP group (32.4-37.4 mmHg) (n=32) and high sPAP group (37.5-55.6 mmHg) (n=31). Associations of serum OPN and SOD levels with sPAP were analysed by univariate and multivariate linear regression analysis. Results: After acute high altitude exposure, the levels of sPAP were significantly increased (P<0.001). There were no differences in age, height, weight, body mass index, percent of Han nationality and smoking among 3 subgroups. However, following acute high altitude exposure, the levels of heart rate, systolic and diastolic blood pressure elevated (all P<0.05), whereas the levels of oxygen saturation were reduced in the total subjects and all subgroups (all P<0.05). Moreover, systolic blood pressure of subjects in the high sPAP group was higher than that in low and middle sPAP groups (both P<0.05), and diastolic blood pressure of subjects in high sPAP group was higher than that in low sPAP group (P<0.05). The serum levels of OPN were increased in total cohort(27.9 (22.5,34.0) μg/L vs. 25.6 (18.4, 33.1) μg/L, P<0.05)， and high sPAP group (P<0.05), whereas no differences were found in serum SOD and MDA levels among groups. Furthermore, the serum level of OPN in high sPAP group was higher than that in low sPAP group at high altitude (P<0.05), and there was a trend for decline in SOD level with increasing sPAP (P>0.05). Results from univariable linear regression analysis showed that the serum levels of OPN (r=0.32, P=0.002) and SOD (r=-0.22，P=0.032) were linearly correlated with sPAP in total cohort after high altitude exposure. Multivariate regression analysis showed that the serum levels of OPN(β=0.310，P=0.002) and SOD (β=-0.199，P=0.043) were independently associated with the levels of sPAP at high altitude. Conclusion: After acute high altitude exposure, the serum level of OPN is positively associated with sPAP, suggesting that OPN may be a novel bio-marker for predicting the increase of pulmonary pressure in response to acute high altitude exposure.
Adolescent ; Adult ; Altitude ; Blood Pressure Determination ; Humans ; Male ; Osteopontin ; Pulmonary Artery ; Systole ; Young Adult

Pulmonary hypertension (PH) is a pathological state with sustained elevation of pulmonary artery (PA) pressure. Since the pathogenesis of PH is mostly irreversible, the disease often comes up with poor prognosis. Pulmonary arterioles are affected by deteriorative changes, such as development of occlusive lesions of thickening of arterial walls. Such processes increase the pulmonary arterial pressure thus lead to consequent injuries such as right ventricle failure. Proliferation, or resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) and fibroblasts, are characteristic changes observed in the PA in pulmonary arterial hypertension (PAH) patients. PAH can either occur idiopathically or come with other diseases. Emerging evidences suggest that pro-inflammatory processes are closely related to the development of PAH. Therefore, it is inferred that immune cells could be the key factors in PAH development. In this review, we summarize the way how each types of immune cells participate in PAH. We would also like to list the current rodent models used for PAH study.
Apoptosis ; Arterial Pressure ; Arterioles ; Fibroblasts ; Heart Ventricles ; Humans ; Hydrogen-Ion Concentration ; Hypertension ; Hypertension, Pulmonary ; Inflammation ; Myocytes, Smooth Muscle ; Prognosis ; Pulmonary Artery ; Rodentia

BACKGROUND: Previous randomized controlled trials of revascularization for atherosclerotic renal artery stenosis (ARAS) were not successful. We investigated the effects of percutaneous transluminal angioplasty with stent insertion (PTA/S) on kidney function and blood pressure (BP) control in patients with ARAS. METHODS: From 2000 to 2017, 47 subjects who underwent PTA/S for ARAS were identified. A high-risk group was defined, composed of patients having one or more of the following clinical presentations: pulmonary edema, refractory hypertension, and rapid deterioration of kidney function. Subjects who met the criteria of ‘kidney function improvement’ or ‘hypertension improvement’ after PTA/S were classified as responders. RESULTS: Twenty-one (44.7%) subjects were classified into the high-risk group. Two subjects (8.0%) in the low-risk group (n = 25) and 5 subjects (27.8%) in the high-risk group (n = 18) showed improvement in kidney function after PTA/S (P = 0.110). In patients with rapid decline of kidney function, estimated glomerular filtration rate improved from 28 (interquartile range [IQR], 10–45) mL/min/1.73 m² to 41 (IQR, 16–67) mL/min/1.73 m² at 4 months after PTA/S, although the difference was not significant (P = 0.084). Regarding BP control, 9 (36.0%) and 14 (77.8%) subjects showed improvement after PTA/S in the low- (n = 25) and high-risk (n = 18) groups, respectively (P = 0.007). In patients with refractory hypertension, the systolic BP dropped from 157 (IQR, 150–164) mmHg to 140 (IQR, 131–148) mmHg at 4 months after PTA/S (P = 0.005). Twenty-five subjects were defined as responders and comprised a significant proportion of the high-risk group (P = 0.004). CONCLUSION: PTA/S might improve BP control and kidney function in patients with ARAS presenting with high-risk clinical features. The optimal application of PTA/S should be based on individual assessment of the clinical significance of renal artery stenosis.
Angioplasty ; Blood Pressure ; Glomerular Filtration Rate ; Humans ; Hypertension ; Kidney ; Pulmonary Edema ; Renal Artery Obstruction ; Renal Artery ; Stents

PURPOSE: The most common method of monitoring cardiac output (CO) is thermodilution using pulmonary artery catheter (PAC), but this method is associated with complications. Impedance cardiography (ICG) is a non-invasive CO monitoring technique. This study compared the accuracy and efficacy of ICG as a non-invasive cardiac function monitoring technique to those of thermodilution and arterial pressure contour. MATERIALS AND METHODS: Sixteen patients undergoing liver transplantation were included. Cardiac index (CI) was measured by thermodilution using PAC, arterial waveform analysis, and ICG simultaneously in each patient. Statistical analysis was performed using intraclass correlation coefficient (ICC) and Bland-Altman analysis to assess the degree of agreement. RESULTS: The difference by thermodilution and ICG was 1.13 L/min/m², and the limits of agreement were −0.93 and 3.20 L/min/m². The difference by thermodilution and arterial pressure contour was 0.62 L/min/m², and the limits of agreement were −1.43 and 2.67 L/min/m². The difference by arterial pressure contour and ICG was 0.50 L/min/m², and the limits of agreement were −1.32 and 2.32 L/min/m². All three percentage errors exceeded the 30% limit of acceptance. Substantial agreement was observed between CI of thermodilution with PAC and ICG at preanhepatic and anhepatic phases, as well as between CI of thermodilution and arterial waveform analysis at preanhepatic phase. Others showed moderate agreement. CONCLUSION: Although neither method was clinically equivalent to thermodilution, ICG showed more substantial correlation with thermodilution method than with arterial waveform analysis. As a non-invasive cardiac function monitor, ICG would likely require further studies in other settings.
Arterial Pressure ; Cardiac Output ; Cardiography, Impedance ; Catheters ; Electric Impedance ; Humans ; Liver Transplantation ; Methods ; Pulmonary Artery ; Thermodilution

BACKGROUND: Static parameters such as central venous pressure and pulmonary artery occlusion pressure, have limitation in evaluation of patients' volume status. Dynamic parameters such as stroke volume variation (SVV), have been used to evaluate intraoperative hemodynamic volume status, in various operations. We examined if SVV is also effective for patients undergoing operation with prone position for fluid management. METHODS: Eighteen patients that received spinal surgery under prone position November 2015 to May 2016, were enrolled. Patients were kept at an SVV value less than 14% during surgery. Changes of pre-, post-operative volume status were evaluated, using transthoracic echocardiography. RESULTS: Mean fluid administered was 1,731.97 ± 792.38 ml. Left ventricular end-diastolic volume was 72.85 ± 13.50 ml before surgery, and 70.84 ± 15.00 ml after surgery (P value = 0.594). Right ventricular end-diastolic area was 15.56 ± 1.71 cm² before surgery, and 13.52 ± 2.65 cm² after surgery (P value = 0.110). Inferior vena cava diameter was 14.99 ± 1.74 mm before surgery, and 13.57 ± 2.83 mm after surgery (P value = 0.080). CONCLUSIONS: We can confirm that fluid management based on SVV is effective, even in prone position surgery. So, SVV, that can be measured by continuous arterial pressure, can be considered a guideline for effective fluid management in spinal surgery.
Arterial Pressure ; Central Venous Pressure ; Echocardiography ; Fluid Therapy ; Hemodynamics ; Humans ; Prone Position ; Pulmonary Artery ; Stroke Volume ; Stroke ; Vena Cava, Inferior

PURPOSE: The efficacy of percutaneous stent implantation for congenital heart disease (CHD) in Korea, where stent availability is limited, has not been determined. This study evaluated the acute and midterm results of stent implantation in different CHD subgroups. METHODS: Stents were implanted in 75 patients with 81 lesions: (1) pulmonary artery stenosis (PAS) group, 56 lesions in 51 patients; (2) coarctation of the aorta (CoA) group, 5 lesions in 5 patients; (3) Fontan group, 13 lesions in 12 patients; (4) ductal stent group, 3 lesions in 3 patients; and (5) other CHD group, 4 lesions in 4 patients. Mean follow-up duration was 2.1 years (0.1–4 years). Medical records were reviewed retrospectively. RESULTS: The minimum lumen diameter (MLD) in PAS and CoA increased from 5.0±1.9 mm and 8.4±1.6 mm to 10.1±3.6 mm and 12.3±2.5 mm, respectively (P<0.01). In the PAS group, pressure gradient decreased from 25.7±15.6 mmHg to 10.4±10.1 mmHg, and right ventricular to aortic pressure ratio from 0.56±0.21 to 0.46±0.19. In the CoA group, the pressure gradient decreased from 50±33 mmHg to 17±8 mmHg. In the ductal stent group, the MLD of the ductus increased from 2.3 mm to 4.3 mm and arterial oxygen saturation from 40%–70% to 90%. No deaths were associated with stent implantation. Stent migration occurred in 3 patients, but repositioning was successful in all. Stent redilation was performed successfully in 26 cases after 29±12 months. CONCLUSION: Percutaneous stent implantation was safe and effective, with acceptable short and mid-term outcomes in Korean CHD patients.
Aortic Coarctation ; Arterial Pressure ; Constriction, Pathologic ; Follow-Up Studies ; Heart Defects, Congenital* ; Humans ; Korea ; Medical Records ; Oxygen ; Pulmonary Artery ; Retrospective Studies ; Stents*

BACKGROUND: Heart transplantation (HTx) can be a life-saving procedure for patients in whom single ventricle palliation or one-and-a-half (1½) ventricle repair has failed. However, the presence of a previous bidirectional cavopulmonary shunt (BCS) necessitates extensive pulmonary artery angioplasty, which may lead to worse outcomes. We sought to assess the post-HTx outcomes in patients with a previous BCS, and to assess the technical feasibility of leaving the BCS in place during HTx. METHODS: From 1992 to 2017, 11 HTx were performed in patients failing from Fontan (n=7), BCS (n=3), or 1½ ventricle (n=1) physiology at Asan Medical Center. The median age at HTx was 12.0 years (range, 3–24 years). Three patients (27.3%) underwent HTx without taking down the previous BCS. RESULTS: No early mortality was observed. One patient died of acute rejection 3.5 years after HTx. The overall survival rate was 91% at 2 years. In the 3 patients without BCS take-down, the median anastomosis time was 65 minutes (range, 54–68 minutes), which was shorter than in the patients with BCS take-down (93 minutes; range, 62–128 minutes), while the postoperative central venous pressure (CVP) was comparable to the preoperative CVP. CONCLUSION: Transplantation can be successfully performed in patients with end-stage congenital heart disease after single ventricle palliation or 1½ ventricle repair. Leaving the BCS in place during HTx may simplify the operative procedure without causing significant adverse outcomes.
Angioplasty ; Central Venous Pressure ; Chungcheongnam-do ; Fontan Procedure ; Heart Defects, Congenital ; Heart Transplantation* ; Heart* ; Humans ; Mortality ; Physiology ; Pulmonary Artery* ; Surgical Procedures, Operative ; Survival Rate ; Vena Cava, Superior*

BACKGROUND AND OBJECTIVES: The clinical characteristics of patients with diastolic dysfunction characterized by a relaxation abnormality with possible elevated filling pressure is remain to be determined. We sought to test whether diastolic stress echocardiography (DSE) is useful for characterization of these patients. METHODS: A total of 120 patients (58 men, mean age of 64±7 years) with E/A ratio < 1.0 (mean±SD, 0.7±0.1) and 10≤ E/e' < 15 at rest echocardiography was enrolled prospectively for supine bicycle exercise up to 50 W. RESULTS: During exercise, 47 patients (39%) showed high left ventricular filling pressure (E/e' > 15, hLVFP) and 40 (30%) developed exercise-induced pulmonary hypertension (systolic pulomary arterial pressure > 50 mmHg, EiPH) without hLVFP. The remaining 33 patients did not show hLVFP or EiPH. The incidence of EiPH with hLVFP was 21% (25/120). By multivariate analysis, age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.00–1.13; p=0.039) and systolic pulmonary artery pressure at rest (OR, 1.14; 95% CI, 1.02–1.27; p=0.02) were associated with EiPH, whereas late diastolic transmitral velocity (OR, 1.04; 95% CI, 1.00–1.08; p=0.03) and diastolic blood pressure (OR, 0.94; 95% CI, 0.90–0.99; p=0.02) were associated with hLVFP during exercise. CONCLUSIONS: Patients with relaxation abnormality and possibly hLVFP showed markedly heterogeneous hemodynamic changes during low-level exercise and DSE was useful to characterize these patients.
Arterial Pressure ; Blood Pressure ; Diastole ; Echocardiography ; Echocardiography, Doppler ; Echocardiography, Stress ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; Incidence ; Male ; Multivariate Analysis ; Prospective Studies ; Pulmonary Artery ; Relaxation

BACKGROUND AND OBJECTIVES: Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding the histopathologic and hemodynamic benefits of MAC treatment at an early stage of PAH is lacking. METHODS: One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis. RESULTS: RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p < 0.05), and the co-administration of SIL showed no additional benefit (45±8%, p > 0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 µL) and end-diastolic volumes (310±86 µL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (−254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 µL, 235±55 µL, 40±10.5 mmHg, and −145±42.1, respectively) and MAC+SIL (109±47 µL, 242±46 µL, 38±9.2 mmHg, and −151±39.2, respectively) (all p < 0.05). However, the MAC and MAC+SIL did not differ (all p > 0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p < 0.05); the 2 treatment groups did not differ. CONCLUSIONS: MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.
Animals ; Atrial Pressure ; Blood Pressure ; Catheters ; Echocardiography ; Fibrosis ; Hemodynamics ; Humans ; Hypertension ; Hypertension, Pulmonary ; Lung ; Models, Animal ; Monocrotaline ; Mortality ; Pathology ; Pulmonary Artery ; Rats ; Sildenafil Citrate

PURPOSE: Abnormal potassium channels expression affects vessel function, including vascular tone and proliferation rate. Diverse potassium channels, including voltage-gated potassium (Kv) channels, are involved in pathological changes of pulmonary arterial hypertension (PAH). Since the role of the Kv1.7 channel in PAH has not been previously studied, we investigated whether Kv1.7 channel expression changes in the lung tissue of a monocrotaline (MCT)-induced PAH rat model and whether this change is influenced by the endothelin (ET)-1 and reactive oxygen species (ROS) pathways. METHODS: Rats were separated into 2 groups: the control (C) group and the MCT (M) group (60 mg/kg MCT). A hemodynamic study was performed by catheterization into the external jugular vein to estimate the right ventricular pressure (RVP), and pathological changes in the lung tissue were investigated. Changes in protein and mRNA levels were confirmed by western blot and polymerase chain reaction analysis, respectively. RESULTS: MCT caused increased RVP, medial wall thickening of the pulmonary arterioles, and increased expression level of ET-1, ET receptor A, and NADPH oxidase (NOX) 4 proteins. Decreased Kv1.7 channel expression was detected in the lung tissue. Inward-rectifier channel 6.1 expression in the lung tissue also increased. We confirmed that ET-1 increased NOX4 level and decreased glutathione peroxidase-1 level in pulmonary artery smooth muscle cells (PASMCs). ET-1 increased ROS level in PASMCs. CONCLUSION: Decreased Kv1.7 channel expression might be caused by the ET-1 and ROS pathways and contributes to MCT-induced PAH.
Animals ; Arterioles ; Blotting, Western ; Catheterization ; Catheters ; Endothelins ; Glutathione ; Hemodynamics ; Hypertension* ; Jugular Veins ; Lung ; Models, Animal* ; Monocrotaline ; Myocytes, Smooth Muscle ; NADPH Oxidase ; Polymerase Chain Reaction ; Potassium ; Potassium Channels ; Potassium Channels, Voltage-Gated* ; Pulmonary Artery ; Rats* ; Reactive Oxygen Species ; RNA, Messenger ; Ventricular Pressure