Endothelial-specific Loss of IFT88 Promotes Endothelial-to-Mesenchymal Transition and Exacerbates Bleomycin-induced Pulmonary Fibrosis.

Intraflagellar transport protein 88 (Ift88) is required for ciliogenesis and shear stress-induced dissolution of cilia in embryonic endothelial cells coincides with endothelial-to-mesenchymal transition (EndMT) in the developing heart. EndMT is also suggested to underlie heart and lung fibrosis, however, the mechanism linking endothelial Ift88, its effect on EndMT and organ fibrosis remains mainly unexplored. We silenced Ift88 in endothelial cells (ECs) in vitro and generated endothelial cell-specific Ift88-knockout mice (Ift88endo) in vivo to evaluate EndMT and its contribution towards organ fibrosis, respectively. Ift88-silencing in ECs led to mesenchymal cells-like changes in endothelial cells. The expression level of the endothelial markers (CD31, Tie-2 and VE-cadherin) were significantly reduced with a concomitant increase in the expression level of mesenchymal markers (αSMA, N-Cadherin and FSP-1) in Ift88-silenced ECs. Increased EndMT was associated with increased expression of profibrotic Collagen I expression and increased proliferation in Ift88-silenced ECs. Loss of Ift88 in ECs was further associated with increased expression of Sonic Hedgehog signaling effectors. In vivo, endothelial cells isolated from the heart and lung of Ift88endo mice demonstrated loss of Ift88 expression in the endothelium. The Ift88endo mice were born in expected Mendelian ratios without any adverse cardiac phenotypes at baseline. Cardiac and pulmonary endothelial cells isolated from the Ift88endo mice demonstrated signs of EndMT and bleomycin treatment exacerbated pulmonary fibrosis in Ift88endo mice. Pressure overload stress in the form of aortic banding did not reveal a significant difference in cardiac fibrosis between Ift88endo mice and control mice. Our findings demonstrate a novel association between endothelial cilia with EndMT and cell proliferation and also show that loss of endothelial cilia-associated increase in EndMT contributes specifically towards pulmonary fibrosis.

Involvement of miR-200b-PKCα signalling in pulmonary hypertension in cor pulmonale model.

The right ventricle (RV) enlargement and pulmonary fibrosis are involved in cor pulmonale. The role of miR-200b in cor pulmonale is less well understood. This study was designed to evaluate the regulatory roles of miR-200b in cor pulmonale. Cor pulmonary mouse model was built via monocrotaline injection of monocrotaline (MCT). The expression of miR-200b in the lungs, RV and left ventricle (LV) are using real-time polymerase chain reaction. The transthoracic echocardiography was employed to determine the effects of miR-200b mimics and Gö6976 injection on MCT mice. The protein levels of protein kinase C α (PKCα), collagen, and fibronectin in the lung, RV, and LV in the mice with and without miR-200b mimics and Gö6976 injection were evaluated using western blot. The expression of miR-200b decreased in MCT mice, while there was no difference in LV. Both the miR-200b mimics and Gö6976 injection reversed the muscularization in the pulmonary artery, reversed RV hypertrophy, reduced RV systolic pressure, wall thickness and pulmonary fibrosis. The injection of miR-200b can reduce the PKCα expression in the lung, RV, and LV. This study confirmed the down-regulation of miR-200b in cor pulmonale. The reverse effects of miR-200b in the present study may provide a potential tool for cor pulmonary treatment.

Correlations of IL-6 and CRP gene polymorphisms with pulmonary heart disease.

OBJECTIVE: To explore the correlations of interleukin-6 (IL-6) and C-reactive protein (CRP) gene polymorphisms with pulmonary heart disease (PHD). PATIENTS AND METHODS: A total of 98 patients with PHD and 102 healthy persons receiving physical examinations were enrolled. Their general clinical information was collected, and the levels of IL-6 and CRP in the plasma were determined. The pulmonary functions and blood gas were detected, and the TaqMan-minor groove binder (MGB) probe was used to detect the polymorphisms of IL-6 rs1800796 and CRP rs1800796. RESULTS: Observation group had higher levels of IL-6 and CRP than control group (p<0.05). The forced expiratory volume in 1 second (FEV1) (%), FEV1/forced vital capacity (FVC) ratio (%), and arterial partial pressure of oxygen (PaO2) in observation group were lower than those in control group (p<0.05), but the arterial partial pressure of carbon dioxide (PaCO2) was higher than that in control group (p<0.05). There were differences in the distribution frequencies of the genotypes and alleles of IL-6 rs1800796 and CRP rs1800796 between the two groups (p<0.05). CONCLUSIONS: IL-6 and CRP are correlated with the onset of PHD, and there are also correlations between the polymorphisms of IL-6 rs1800796 and CRP rs2794521 and the disease.

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling.

The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular-vascular uncoupling and adverse ventricular-ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force-specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.

Aerobic Exercise Promotes a Decrease in Right Ventricle Apoptotic Proteins in Experimental Cor Pulmonale.

Pulmonary arterial hypertension is characterized by progressive increases in resistance and pressure in the pulmonary artery and Cor pulmonale. The effect of exercise on hydrogen peroxide-dependent signaling in the right ventricle (RV) of Cor pulmonale rats was analyzed. Rats were divided into sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM) groups. Rats underwent exercise training (60% of VO2 max) for 5 weeks, with 3 weeks after monocrotaline injection (60 mg/kg intraperitoneally). Pulmonary resistance was enhanced in SM (2.0-fold) compared with SC. Pulmonary artery pressure was increased in SM (2.7-fold) and TM (2.6-fold) compared with their respective controls (SC and TC). RV hypertrophy indexes increased in SM compared with SC. Hydrogen peroxide was higher in SM (1.7-fold) than SC and was reduced by 47% in TM compared with SM. p-Akt was increased in TM (2.98-fold) compared with SM. The Bax/Bcl-2 ratio and caspase 3 were also increased (2.9-fold and 3.9-fold, respectively) in SM compared with SC. Caspase 3 was decreased in TM compared with SM (P < 0.05). Therefore, exercise training promoted a beneficial response by decreasing hydrogen peroxide concentrations, and consequently, apoptotic signaling in RV.

[Activation of neurohormonal system as an independent mechanism of heart remodeling in patients with chronic obstructive pulmonary disease].

AIM: To evaluate the contribution of activation of cytokines and renin-angiotensin-aldosterone system to heart remodeling in patients with chronic obstructive pulmonary disease in the course of a 2 year study and to estimate its relation to severe pulmonary hypertension. MATERIALS AND METHODS: 117 patients with COPD underwent measurement of TNFα, IL-6 levels and renin levels, spirometry and echocardiography (mean pressure in pulmonary artery, MPPA)). The data obtainedwere compared with the degree of remodeling of right and left ventricles. After 2 years 30 and 33 of the 63 patients were referred to groups with aggressive and moderate remodeling of the right ventricle respectively. Regressive analysis was used to detect predictors of aggressive remodeling. RESULTS: Initial remodeling severity and rate showed stronger correlation with TNFα, IL-6 levels and renin levels than with MPPA. Multifactor analysis demonstrated that renin activity and creatinine level were the most reliable predictors of remodeling (p = 0.041 and 0.049 respectively). CONCLUSION: Neurohormonal and imunno-inflammatory changes stimulate remodeling of right and left heart chambers. They independently affect myocardium and their influence is only partly mediated through exacerbation of pulmonary hypertension.

[Pathophysiological characteristics of rat pulmonary hypertension and cor pulmonale induced by monocrotaline].

OBJECTIVE: To explore the mechanism of pulmonary hypertension and Cor Pulmonale rat models induced by monocrotaline (MCT). METHODS: Twenty Wistar male rats were randomly divided into normal control group and model group (n= 10), which received a single intraperitoneal injection of MCT solution (50 mg/kg , the first day) or dissolvant, respectively. On day 28 after MCT administration, the hemodynamic parameters were assessed; levels of tumour necrosis factor-alpha (TNF-alpha), nitric oxide (NO), endothelin-1 (ET-1), B-type natriuretic peptide(BNP) in pulmonary tissue or blood were measured using radio immunoassay or nitrate reductase method. RESULTS: 28 days after MCT injection, compared with control group, right ventricle systolic pressure (RVSP) increased and heart rate(HR), mean arterial pressure (MAP) decreased; Levels of TNF-alpha, NO, ET-1 in pulmonary tissue or blood increased significantly in MCT group. CONCLUSION: The potential mechanism of MCI- induced pulmonary hypertension and Cor Pulmonale rat models associates with increasing TNF-alpha, NO, ET-1 levels in vivo, which results from inflammatory injury of lung tissue and blood vessels induced by MCT.

[Effects of tetramethylpyrazine on fractalkine and tumor necrosis factor-alpha expression in patients with chronic pulmonary heart disease].

OBJECTIVE: To reveal the relationship of chronic pulmonary heart disease (CPHD) with the chemotactic factor Fractalkine (FKN) and tumor necrosis factor-alpha (TNF-alpha), and to explore the action mechanism of tetramethylpyrazine (TMP) for suppressing pulmonary hypertension. METHODS: Patients with CPHD were randomly assigned to two groups, 19 in Group A and 16 in Group B, and a control group (group C) consisting of 18 healthy adults was setup. Conventional treatment were given to all patients, which consisted of Piperacillin 3. 375 g iv dripping twice a day, Levofloxacin 0.6 g + Ambroxol 60 mg + Doxofylline 0.2 g iv dripping once a day, all for 10-14 days, and acid-base and electrolytes balance in patients were monitored and corrected. At the same time, TMP (trade name: Chuanqing, containing 120 mg of TMP in a 2 mL ampoule) was given additionally to patients in Group B at the dosage of 240 mg/d by adding in 250 mL of normal saline via iv dripping. Serum levels of FKN and TNF-alpha were detected before and after treatment by enzyme-linked immunoassay, and the change of mean pulmonary arterial pressure (mPAP) was measured as well. RESULTS: Before treatment, difference of FKN and TNF-alpha levels between the two patients' groups were insignificant (P > 0.05), but all higher than those in Group C respectively (P < 0.01). While after treatment, the two indices and mPAP levels in Group B were statistically lower than those before treatment, also than those in Group A. Regression analysis showed a positive correlation between TNF-alpha and FKN (r = 0.662, P < 0.001). CONCLUSIONS: A high blood FKN and TNF-alpha expression state exists in CPHD patients, which could be suppressed by TMP, and these suppressive effects may be one of the important mechanisms responsible for the pulmonary arterial pressure lowering action of TMP.

Mechanisms underlying early development of pulmonary vascular obstructive disease in Down syndrome: An imbalance in biosynthesis of thromboxane A2 and prostacyclin.

Patients with Down syndrome (DS) and a left-to-right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A(2) and prostacyclin (PGI(2)) in four groups of infants, cross-classified as shown below, by measuring the urinary excretion levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha): DS infants with a left-to-right shunt and PH (D-PH, n = 18), DS infants without congenital heart defect (D-C, n = 8), non-DS infants with a left-to-right shunt and PH (ND-PH, n = 12), and non-DS infants without congenital heart defect (ND-C, n = 22). The urinary excretion ratios of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) in the D-PH, D-C, ND-PH, and ND-C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) was higher in the presence of DS (P < 0.001), independently of the presence of PH (P = 0.297). The predominant biosynthesis of TXA(2) over PGI(2), leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left-to-right shunt.

Impacto de la anemia en la EPOC / Impact of anemia on COPD

La frecuencia de la anemia puede ser más elevada de lo esperado en los pacientes que padecen una enfermedadpulmonar obstructiva crónica (EPOC). En algunos estudios se han detectado prevalencias que alcanzanun 33%, lo que contrasta con la idea habitual que relaciona la EPOC con la poliglobulia secundaria. Entrelos factores de riesgo que se asocian con el desarrollo de una anemia en estos pacientes se encuentranla edad avanzada, la gravedad de la obstrucción al fl ujo aéreo y la disminución del índice de masa corporal.La anemia es, además de un trastorno frecuente en la EPOC, un índice de mal pronóstico y determina unamorbimortalidad mayor en esta enfermedad. En relación con el tratamiento, a pesar de los posibles benefi -cios clínicos que podrían derivarse de la corrección de la anemia en estos casos, las evidencias científi casque certifi can la importancia de su efecto en el pronóstico de la EPOC son aún escasas(AU)

The frequency of anemia may be higher than expected in patients with chronic obstructive pulmonarydisease (COPD). Some studies have detected a prevalence of 33%, contrasting with the common idea thatassociates COPD with secondary polyglobulia. Among the risk factors associated with the development ofanemia in these patients are advanced age, the severity of airfl ow obstruction and reduction in body massindex. In addition to being a frequent disorder in COPD, anemia is also a poor prognostic factor and leads togreater morbidity and mortality in this disease. Despite the possible clinical benefi ts of successfully treatinganemia in these patients, the scientifi c evidence supporting the importance of its effect on the prognosis ofCOPD is scarce(AU)

[Endothelial dysfunction mediators in patients with chronic cor pulmonale].

Forty-nine sourses of Russian and foreign literature dedicated to the role of endothelial dysfunction in the development of pulmonary hypertension and chronic cor pulmonale were analyzed. Data on endothelium-dependent vasoactive mediators are presented in the article.

Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats.

We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.

Antioxidant and oxidative stress changes in experimental cor pulmonale.

Although right heart failure (RHF) contributes to 20% of all cardiovascular complications, most of the information available on RHF in general is based on the experiences with left heart failure. This study on RHF investigates changes in antioxidants and oxidative stress which are suggested to play a role in the transition from hypertrophy to failure. RHF subsequent to pulmonary hypertension was produced in rats by a single injection of monocrotaline (MCT, 60 mg/kg, i.p.). Based on hemodynamic, clinical and histopathologic observations, the animals were grouped in three functional stages at 1-, 2- and 6-week post-injection periods. In the 1-week group, RV pressure overload and hypertrophy, and a mild increase in antioxidant enzymes was seen. In the 2-week group, compensated HF, a significant increase in antioxidant enzymes, an increase in septal (IVS) wall thickness and leftward displacement of IVS without change in LV free wall were seen. In the 6-week group, lung and liver congestion, RVF and dilation, a decrease in antioxidant enzyme activities, increase in lipid peroxidation and severe bulging of the IVS into the left ventricle were seen. These changes in the hemodynamic, biochemical and histopathologic characteristics suggest that in early stages of MCT-induced pulmonary hypertension at 1 and 2 weeks, RV hypertrophy was accompanied by sustained hemodynamic function and an increase in antioxidant reserve. In the later stage at 6 weeks, clinical RHF was associated with abnormalities of the right heart systolic and diastolic function along with a decrease in antioxidant reserve. These biphasic changes in RV antioxidant enzymes, i.e. an increase during hypertrophy and a decrease in failure may suggest a role of oxidative stress in the pathogenesis of right ventricular dysfunction.

YM598, an orally active ET(A) receptor antagonist, ameliorates the progression of cardiopulmonary changes and both-side heart failure in rats with cor pulmonale and myocardial infarction.

The effects of the novel, selective endothelin-A (ETA) receptor antagonist YM598 on both-side heart failure were investigated. Right-side heart failure secondary to pulmonary hypertension was produced by a single subcutaneous injection of 60 mg/kg monocrotaline, and post-ischemic congestive left-side heart failure (CHF) produced by surgical left coronary artery ligation. In right-side heart failure rats, oral YM598 (0.1 and 1 mg/kg for 4 weeks), but not bosentan (30 mg/kg), significantly inhibited the progression of pulmonary hypertension and the development of right ventricular hypertrophy. YM598 also improved hypoxemia and morphological pulmonary lesions in these rats. In CHF rats, moreover, long-term oral administration of YM598 (1 mg/kg/day for approximately 30 weeks) significantly ameliorated their poor survival rate (P < 0.05). In the measurement of cardio-hemodynamic parameters, YM598 improved the contractile/diastolic capacity of the left ventricle and the preload in the right ventricle to the levels seen in sham-operated rats. YM598 also markedly inhibited both ventricular hypertrophy and pulmonary congestion, as well as lowering high plasma brain natriuretic peptide levels in CHF rats. These findings suggest that YM598 may have a clinical benefit with regards to ameliorating the cardiopulmonary changes of right-side heart failure, and the cardiac dysfunction and mortality/morbidity of CHF.

Endoxin:a major factor regulating cardiovascular system.

Endoxin is a factor with a digitalis-like biological activity. It is a Na+ pump inhibitor and may be an endogenous medium of digitalis receptor. There are abnormal plasma levels of endoxin in some pathophysiologic states such as hypertension, acute myocardial infarction, arrhythmia, heart failure, etc. Some studies have demonstrated that the abnormal endoxin levels may be implicated in pathogenesis of these diseases or pathophysiologic process involved. Therefore, to clarify the effects of endoxin has much significance in understanding pathogenesis, prevention and treatment of hypertension and other cardiovascular diseases.

Tabaco y sistema cardiopulmonar en el anciano / Tobacco and cardiopulmonary risk in the elderly

Los componentes del humo del tabaco producen efectos sobre las plaquetas, endotelio vascular, lipoproteínas, factores hemostáticos y condiciones hemodinámicas, que contribuyen a la aparición de alteraciones cardiovasculares y pulmonares tanto inmediatamente como a largo plazo, y estos efectos perjudiciales se dan también en los ancianos, como lo demuestran recientes estudios epidemiológicos. Las evidencias demuestran varios mecanismos de acción de algunos de los componentes del tabaco (sobre todo de la nicotina y del monóxido de carbono) que contribuyen a este aumento de riesgo. Hay una relación dosis-efecto, y el abandono del tabaquismo conlleva una reducción del riesgo cardiovascular y respiratorio, que puede llegar para algunas enfermedades a niveles similares a los de las personas que nunca han fumado, aunque esto no se ha probado aún en los ancianos (AU)

The components of tobacco smoke produce effects over the platelet, vascular endothelium, lipoproteins, haemostatic factors and haemodinamic conditions wich contribute to the appearence of cardiovascular and pulmonar alterations as inmediately as long term. This negative effects are also given in elderly, as recent epidemiological studies show. The evidences show several action mecanism of some tobacco components (overall nicotine and CO), which contribute to the risk increase. There is a relation dose-effect and the tobacco cesation gives a reduction of cardiovascular and pulmonar risk, which can become similar levels to people who never smoke for some illness (AU)

Use of [123I]-BMIPP myocardial scintigraphy for the clinical evaluation of a fatty-acid metabolism disorder of the right ventricle in chronic respiratory and pulmonary vascular disease.

The objective of this study was to evaluate whether or not right ventricle (RV) uptake of iodine-123-labelled-beta-methyliodophenylpentadecanoic acid ([123I]-BMIPP) correlated with the degree of right ventricular pressure overload (RVPO). Myocardial scintigraphy of [123I]-BMIPP and thallium-201 (201Tl) was performed on 46 patients with RVPO. We determined the right ventricle (RV)/left ventricle (LV) ratio = (radioactivities of RV)/(radioactivities of LV), and the RV metabolic index (RVMI) = (RV/LV ratio of [123I]-BMIPP)/(RV/LV ratio of 201Tl). We also evaluated the correlation between RVMI and mean pulmonary arterial pressure (mPAP), and between RVMI and total pulmonary resistance (TPR). Significant correlations were found between the RV/LV ratio of [123I]-BMIPP and mPAP and between the RV/LV ratio of [123I]-BMIPP and TPR. In addition, a significant negative correlation was observed between RVMI and mPAP and between RVMI and TPR. RVMI declined as RVPO increased, suggesting the presence of a fatty-acid metabolism disorder of the RV. Moreover, [123I]-BMIPP myocardial scintigraphy could be useful for evaluating a disorder of the fatty-acid metabolism of the RV with RVPO.

[Clinical study of fibrinolysis indicators in patients with chronic pulmonary heart disease].

OBJECTIVE: To investigate the change of D-dimer and other fibrinolysis indicators in patients with chronic pulmonary heart disease. METHODS: The fibrinolytic activity of plasma was measured in 42 patients with chronic pulmonary heart disease and in 20 controls (matched with sex and age). RESULTS: The D-dimer level was significantly higher in exacerbated patients than in controls (P < 0.001). The fibrinolytic activity in patients was lower than in controls. The plasma fibrinolytic activity was positively correlated with PaO2 and negativly correlated with PaCO2. CONCLUSIONS: The depressed fibrinolysis may be associated with hypercoagulability state of chronic pulmonary heart disease and contributes to thrombi in small pulmonary arteries and arterioles. D-dimer can be used in diagnosis of thrombi formation in small pulmonary arteries and arterioles. Patients with chronic pulmonary heart disease can be treated with fibrinolysis drugs.

[Relationship between left cardiac function and oxygen transport of cor pulmonale during acute attack at high altitude].

OBJECTIVE: Relationship between left cardiac function and oxygen transport in the patients with cor pulmonale during acute attack at high altitude was studied to benefit prevention and treatment of cor pulmonale. METHOD: 20 cases were divided into 16 as a surviving group and 4 as a death group. CO was determined by Swan-Ganz catheter from internal carotid vein to pulmonary artery directly. RESULT: (1) CI in the patients decreased (2.9 +/- 0.4 L.min-1.m-2). mPAP (4.9 +/- 1.3 kPa) and PAWP (1.5 +/- 0.8 kPa) increased. LVSWI (35 +/- 11 g.cm-1.min-1) dropped. (2) above Indicies in surviving group improved after comprehensive treatment. CI and LVSWI increased. But LVSWI in death group continued to decline. mPAP and PAWP were not changed; (3) There was significant corelation between LVSVI and DO2(r = 0.4318, P < 0.05). CONCLUSION: LVSWI of cor pulmonale could affect DO2 level directly and closely relate to prognosis.

Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease.

BACKGROUND: Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity. METHODS: Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 < 35% predicted with CP, n = 15; group 2, FEV1 < 35% predicted without CP, n = 15; group 3, FEV1 > 35% predicted, n = 23). Seventeen normal subjects served as controls. RESULTS: All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p < 0.01 ANOVA). In all subjects % predicted FEV1 correlated slightly with PLNO but not with PNO. CONCLUSION: Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.