Changes In Pulmonary Circulation Research Articles

Clinical and experimental parallels in the assessment of microcirculatory dysfunctions of the lungs in thoracic radiology

Introduction. Chronic obstructive disease (COPD) and thromboembolism of the branches of the pulmonary artery or pulmonary embolism (PE) remain the most common and socially significant lung diseases. Circulatory disorders in these pathologies play a critical role in the development of the disease. Radiation techniques, such as computed tomography/angiography and single-photon emission computed tomography (SPECT), are the leading ones in recognizing changes in the lung parenchyma and vessels. Many questions can be successfully solved experimentally. The main radiation techniques used to study the vascular bed when modeling lung diseases in experimental animals are microangiography and perfusion scintigraphy. Purpose. To show the capabilities of radiation diagnostic methods for identifying vascular disorders in COPD and PE in experiments and clinical manifestations. Material and methods. A clinical and experimental comparison of pulmonary circulation changes during COPD and PE was carried out based on the results of perfusion scintigraphy/SPECT in 55 rats with simulated COPD- like condition and 622 patients with COPD of varying severity, as well as 58 rats with simulated PE and 180 patients with PE. Results. When modelling lung diseases (PE and COPD), the results similar to blood circulation and structural changes in the lung parenchyma in patients with these nosologies were obtained. In COPD, changes in the lung parenchyma correlated with disturbances in functional indicators (microcirculation, PaO2, PaCO2, DSLzd, DLco/VA, SDPA) and increased levels of endothelin-1 (r=0.72) and endothelial growth factor (VEGF-A) (r=0.79). Analysis of experimental and clinical data on PE showed the importance of identifying minor forms of thromboembolism. Conclusion. 1. Persistent microcirculatory dysfunctions in the pulmonary circulation play an important role in the pathogenesis of chronic broncho-obstructive pathology. After just 7 days, initial signs of emphysema can be detected in the ischemic area of the lung tissue, and by the 60th day typical bullous cavities can be detected. 2. In the chronic course of minor forms of thromboembolism of small branches of the pulmonary artery, local emphysema is formed. 3. At the early stages of COPD formation, regional zones of emphysematous restructuring of the lung tissue with a predominance of ventilation dysfunctions and zones of «compressive ischemia» with prevailing vascular disorders are formed. As the pathological process progresses, the ischemia factor acquires independent significance in the pathogenesis of the disease.

Hemodynamic and Respiratory Changes following Prone Position in Acute Respiratory Distress Syndrome Patients: A Clinical Study.

Limited data are available for the oxygenation changes following prone position in relation to hemodynamic and pulmonary vascular variations in acute respiratory distress syndrome (ARDS), using reliable invasive methods. We aimed to assess oxygenation and hemodynamic changes between the supine and prone posture in patients with ARDS and identify parameters associated with oxygenation improvement. Eighteen patients with ARDS under protective ventilation were assessed using advanced pulmonary artery catheter monitoring. Physiologic parameters were recorded at baseline supine position, 1 h and 18 h following prone position. The change in the Oxygenation Index (ΔOI) between supine and 18 h prone significantly correlated to the concurrent change in shunt fraction (r = 0.75, p = 0.0001), to the ΔOI between supine and 1 h prone (r = 0.73, p = 0.001), to the supine acute lung injury score and the OI (r = -0.73, p = 0.009 and r = 0.69, p = 0.002, respectively). Cardiac output did not change between supine and prone posture. Moreover, there was no change in pulmonary pressure, pulmonary vascular resistances, right ventricular (RV) volumes and the RV ejection fraction. The present investigation provides physiologic clinical data supporting that oxygenation improvement following prone position in ARDS is driven by the shunt fraction reduction and not by changes in hemodynamics. Moreover, oxygenation improvement was not correlated with RV or pulmonary circulation changes.

Echocardiography-Assessed Changes of Left and Right Ventricular Cardiac Function May Correlate with Progression of Advanced Lung Cancer-A Generating Hypothesis Study.

Simple SummaryLung cancer often coexists with cardiovascular diseases. Due to its specific location, lung cancer affects pulmonary circulation and leads to symptoms of dyspnea. If lung cancer is in an inoperable stage, the early response to cancer treatment determines prognosis. There are studies showing that advanced cancer, especially lung cancer, can be interpreted as advanced heart failure. This publication confirms that the progression of advanced inoperable lung cancer affects a number of parameters of right and left ventricular function. Importantly, the diagnosis of tumor progression may occur at the same time as the diagnosis of a cardiotoxic effect of cancer treatment. Cardio-oncology specialists should plan further research into these correlations and possible preventive strategies or care management.Advanced lung cancer causes damage to lung tissue and the alveolar–capillary barrier, leading to changes in pulmonary circulation and cardiac function. This observational study included 75 patients with inoperable lung cancer. Two echocardiographic assessments were performed: one before the initiation of systemic anticancer therapy and another after the first radiological evaluation of the efficacy of anticancer treatment. In retrospective analysis, diagnosis of early cancer progression was associated significantly (p < 0.05) with some echocardiographic changes: a decrease in EF of at least 5 percentage points (OR = 5.78), an increase in LV GLS of 3 percentage points (OR = 3.81), an increase in E/E′ ratio of at least 3.25 (OR = 3.39), as well as a decrease in RV free wall GLS of at least 4 percentage points (OR = 4.9) and an increase in FAC of at least 4.1 percentage points (OR = 4.9). Cancer therapeutics-related cardiac dysfunction was diagnosed in accordance with the definition of the International Cardio-Oncology Society and was found more frequently in patients with radiologically confirmed lung cancer disease progression (p = 0.003). In further prospective studies, the hypothesis about the possible coexistence of the cardiotoxic effect of cancer therapy and cardiac dysfunction related to the progression of inoperable lung cancer should be clarified.

Assessment of pulmonary hemodynamics and stress-induced pulmonary hypertension in clinical practice

Pulmonary hypertension (PH) is currently determined by the mean pulmonary artery pressure (PAPmean) increase, which in turn is associated with a number of parameters, such as cardiac output (CO), pulmonary vascular resis-tance (PVR) and left atrial pressure. Therefore, changes in PAP mean during exercise cannot be discussed apart from the listed indicators. Probably, this was one of the reasons for the absence of an accurate hemodynamic de-termination of stress-induced PH. However, today it has been revealed that PAP at rest increases only when ≥50% of pulmonary microcirculation is off, and for the earliest detection of the problem it is advisable to use factors that lead to increase of CO and PVR, one of them is exercise. Moreover, clinicians often observe that the anamnesis of PH starts from complaints, associated with exercise. Mo-dern non-invasive technologies (stress-echocardiogra-phy, cardiopulmonary exercise testing) provide very de-tailed data not only about the pulmonary circulation, but also about ventilator function, blood gas composition, structural and functional changes in the heart. Stress-in-duced PH is defined as combination of normal mean pulmonary artery pressure values (PAPmean &lt;25 mm Hg) at rest and increase of PAPmean &gt;30 mm Hg during exercise, as well as PVR &gt;3 WU, however, this definition isn’t generally accepted. As an alternative, to determine stress-induced PH, it was proposed to evaluate PAPmean/CO curve, that excludes the influence of peak hemody-namic parameters. The pulmonary vessels distensibility and ventriculo-arterial coupling represent promising pa-rameters for complete characterization of the pulmonary circulation changes during exercise.

Control Study of Short-Term Aftereffect in Diving Exposure Related Pulmonary Ventilation Function

Objective: Ventilation attenuation often happened in professional divers due to long-term cumulative effects in diving exercises. By case-control experiments, we observed the immediate effects of pulmonary ventilation before and after the exposure of 12m-depth underwater for 20 min to discuss the relationships between the short-term and long-time effects caused by diving environment. Methods: Participants were randomly assigned into the Experimental Group (EG) who stayed for 20 min under 12-m water environment or the Control Group (CG) who stayed in hyperbaric chamber under the pressure of 2.2ATA. Pulmonary ventilation function parameters including VC, FVC, MVV and MV were detected respectively before and after hyperbaric exposure by the Spirometer. Immediate effects of pulmonary ventilation before and after diving were compared by paired t test to reveal the different influence caused by environmental pressure. Results: The value of VC appears to rise while the MV, MVV were detected decreased after the exposure of 2.2ATA of environment pressure for 20min in the two groups. VC increased more significantly in the CG (t=-1.26, p=0.23) after hyperbaric exposure, that leads to the FEV1.0%t (=FEV1.0/VC %) increase in EG (t=-0.73, p=0.48) while decrease in CG (t=0.42, p=0.17). The same trend in VC, MV and MVV after high pressure exposure in the two groups mainly due to the effect of common factors –the pressure. In addition to the impact of the pressure itself, EG members also face diving related immersion effect, influence of diving equipment load and water under low temperature. The FVC is detected decreased in EG (t=1.21, P =0.25) while it increased in CG (t=-0.42, P =0.68) , but the differences are not significant and couldn’t affect the measured FEV1.0% (=FEV1.0/FVC %) values showed both increasing in EG (t=-1.48, P =0.16) and in CG (t=-0.23, P =0.82). The expiratory flow rate including PEF, FEF25-75, MEF75, MEF50 increased in EG (t are -0.72, -0.69, -0.87 and -0.36 respectively with P all greater than 0.05) while decreased in CG (t are 1.67, 0.50, 1.53 and 0.71 respectively with P all greater than 0.05). MEF25 is the expiratory flow index of not affected by respiratory muscle force and the measured values of MEF25 increased in the EG (t=-0.68, P =0.51) and in the CG (t=-0.36, P =0.72). Conclusion: Water immersion and water temperature during diving exposure could cause and accelerate hemodynamic changes in pulmonary circulation induced pulmonary interstitial edema and led to the increase of external respiratory work. Instant effects of diving exposure in the study are quite consistent with the long-term cumulative effect of professional divers in previous research, which is FVC reduced because small airway become narrower. The results illustrate even the small depth of short-range diving exercise have definite influences on pulmonary ventilation, which mainly comes from the environmental factor but not the pressure increases.

The peculiarities of pulmonary macro- and microhemodynamics changes after treatment with agonists and blockers of cholinoceptors

Background. The pulmonary arterial and venous vessels are innervated by parasympathetic cholinergic nerves. However, the studies, performed on the isolated rings of pulmonary vessels, can not give answer to the question about the role of cholinergic mechanisms in the changes of pulmonary circulation in full measure.&#x0D; Aim. The comparative analysis of the changes of the pulmonary macro- and microhemodynamics after acetylcholine, atropine, pentamine and nitroglycerine treatment.&#x0D; Materials and methods. The study was carried out on the anesthetized rabbits in the condition of intact circulation with the measurement of the pulmonary artery pressure and flow, venae cavae flows, cardiac output, and also on isolated perfused lungs in situ with stabilized pulmonary flow with measurement of the perfused pulmonary artery pressure, capillary hydrostatic pressure, capillary filtration coefficient and calculation of the pulmonary vascular resistance, pre- and postcapillary resistances.&#x0D; Results. In the conditions of intact circulation after acetylcholine, pentamine and nitroglycerine treatment the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance did not change as a result of decreasing of pulmonary artery flow and left atrial pressure due to diminution of venous return and venae cavaе flows. On perfused isolated lungs acetylcholine caused the increasing of pulmonary artery pressure, capillary hydrostatic pressure, pulmonary vascular resistance, pre- and postcapillary resistance and capillary filtration coefficient. After M-blocker atropine treatment the indicated above parameters of pulmonary microcirculation increased, on the contrary, after N-blocker pentamine treatment they decreased. Nitroglycerine infusion caused less decreasing of the parameters of pulmonary microcirculation in comparison with effects of pentamine, but capillary filtration coefficient decreased to a greater extent. These data indicate that nitroglycerine decreases endothelial permeability of pulmonary microvessels.&#x0D; Conclusion. After activation or blockade of cholinergic mechanisms in the condition of intact circulation the calculated parameter of pulmonary vascular resistance is depended from the ratio of the pulmonary artery pressure and flow and left atrial pressure, which are determined by the venous return. The different character of the changes of pulmonary microcirculatory parameters after M-blocker atropine and N-blocker pentamine treatment is evidence of reciprocal relations of M- and N-cholinoceptors in the nervous regulation of the pulmonary microcirculatory bed.

Changes in Pulmonary Circulation in Experimental Model of Pulmonary Thromboembolism after Carvedilol Treatment

In experiments on isolated perfused rabbit lungs, we studied changes in the pulmonary microcirculation in response to carvedilol injection and after modelling pulmonary thromboembolism under conditions of α1- and β1,2-adrenoceptor blockade with this drug. Carvedilol had mainly vasodilator effects on the pulmonary arterial vessels; the pulmonary venous resistance increased and the capillary filtration coefficient remained unchanged under these conditions. In case of pulmonary thromboembolism against the background of carvedilol treatment, the increase in precapillary resistance and the capillary filtration coefficient was more pronounced that in the control, but the postcapillary resistance increased to a lesser extent. The increase in the capillary filtration coefficient is a result of elevated precapillary resistance and enhanced endothelial permeability.

Myeloid-Derived Suppressor Cells and Pulmonary Hypertension

Myeloid–derived suppressor cells (MDSCs) comprised a heterogeneous subset of bone marrow–derived myeloid cells, best studied in cancer research, that are increasingly implicated in the pathogenesis of pulmonary vascular remodeling and the development of pulmonary hypertension. Stem cell transplantation represents one extreme interventional strategy for ablating the myeloid compartment but poses a number of translational challenges. There remains an outstanding need for additional therapeutic targets to impact MDSC function, including the potential to alter interactions with innate and adaptive immune subsets, or alternatively, alter trafficking receptors, metabolic pathways, and transcription factor signaling with readily available and safe drugs. In this review, we summarize the current literature on the role of myeloid cells in the development of pulmonary hypertension, first in pulmonary circulation changes associated with myelodysplastic syndromes, and then by examining intrinsic myeloid cell changes that contribute to disease progression in pulmonary hypertension. We then outline several tractable targets and pathways relevant to pulmonary hypertension via MDSC regulation. Identifying these MDSC-regulated effectors is part of an ongoing effort to impact the field of pulmonary hypertension research through identification of myeloid compartment-specific therapeutic applications in the treatment of pulmonary vasculopathies.

Mechanisms for compensation of pulmonary hypertension in chronic obstructive pulmonary disease

Despite multiple risk factors of pulmonary hypertension (PH) are known, the true incidence of PH remains undefined in patients with severe bronchial obstruction. Objective. The aim of the study was to identify mechanisms of compensation of the increase in pulmonary artery pressure and to determine their prognostic role. Design and methods. The results of a complex clinical and radiological studies of 200 patients with COPD II (B), and 207 patients with COPD III (D), and COPD IV (D), (GOLD 2017) were analyzed. A comparative analysis of changesin pulmonary circulation in patients (n = 8) with primary PH was performed. Male subjects predominated among the examined patients with COPD (90,6 %), the average age of patients with COPD II was 54,0 ± 6,3 years, in patients with COPD III–IV stages — 63,9 ± 5,8 years. The average age of patients with primary PH was 38,7 ± 7,9 years. The following diagnostic methods were performed: single-photon emission computer tomography, multidetector computed tomography, external respiration function, echocardiography. Results. In patients with COPD II (B), both ventilation and perfusion disorders developed, the diffusion capacity of the lungs decreased and the intrapulmonary shunting of the blood occurred. Despite overall decrease in pulmonary perfusion, local zones of increased blood flow appeared in the unchanged pulmonary parenchyma. This compensation mechanism was observed in 54,6 % of patients and was accompanied by partial decrease of pressure in the pulmonary artery to values close to normal. In severe COPD, 44,4 % patients developed hyperperfusion zones, but without any compensatory effect. In such cases, pressure reduction in the pulmonary artery system was promoted by the development of blood bypass, which was observed only in 10 % cases. Conclusions. We can speculate that the mechanism of compensation of increased pressure in the pulmonary artery and reduction of PaO2 results from the development of local zones of increased blood flow in the unchanged pulmonary parenchyma, but in severe bronchial obstructive pathology it causes the formation of blood shunting.

Pulmonary Vasoconstriction and Vascular Remodeling Play Role in Reactive Pulmonary Hypertension in Rats

IntroductionThe majority of clinical cases of pulmonary hypertension (PH) are caused by left heart failure. Some patients with venous PH induced by left heart pressure overload develop increase in resistance in the arterial part of the pulmonary circulation (reactive PH). We developed a new animal model of reactive PH caused by left heart pressure overload. We tested hypothesis that pulmonary arterial vasoconstriction and/or pulmonary vascular remodeling play role in our rodent model of reactive PH.MethodsLeft heart pressure overload was induced in adult male Wistar rats by partial intravascular obstruction of the ascending aorta. Three weeks later the experimental rats (group E, n=6) were compared to controls (group C, n=7). In isolated lungs perfused with salt solution with albumin we studied hemodynamic changes in pulmonary circulation by analysis of perfusion pressure increments induced by increasing perfusion flow (P/Q relationship). The P/Q relationship measurement was repeated after adding sodium nitroprusside into perfusate to reveal presence of pulmonary arterial vasoconstriction. In lung histology we counted remodeled peripheral pulmonary vessels in the group E compared to controls.ResultsThe slope of the P/Q relationship was significantly increased in the group E compared to controls (0.112±0.003 mmHg.mL−1.min−1 vs. 0.0046±0.002 mmHg.mL−1.min−1; p&lt;0.0001). Sodium nitroprusside did not alter the slope in controls (0.043±0.002 mmHg.mL−1.min−1). In the group E, sodium nitroprusside reduced the slope to a value not different from that in controls (0.044±0.001 mmHg.mL−1.min−1). In lung histology, 74 % of the small pulmonary vessels had muscularized media in the group E, compared to only 24 % in controls (p&lt;0.01).ConclusionPulmonary vasoconstriction and pulmonary vascular remodeling are involved in the new model of reactive pulmonary hypertension in rats.Support or Funding InformationGrants: GAUK 210216 and GACR 17‐11223SThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

About differences in systemic and pulmonary circulation in the cases of metabolic acidosis after cardio surgery

Objective - to evaluate changes in systemic and pulmonary circulation in the cases of metabolic acidosis (MetAcid) after CABG. Material and metods. Study enrolled 114 patients. In the postoperative period we sampled arterial and mixed venous blood for acid-base analysis. At the same time point we measured a hemodynamic parameters). Results. We found opposite changes in systemic circulation in the cases with different types of MetAcid. SIR was associated with vasoplegia and increased stroke volume (SV). The cases of AHF showed decrease in SV and vasoconstriction. We found one-direction changes in pulmonary circulation in the cases with different types of MetAcid. There were a tendency toward an increase in the pulmonary vascular resistance, raise in the PAPmean in both subgroups.

Nadciśnienie płucne w przebiegu chorób lewego serca — aktualne leczenie i kierunki rozwoju terapii

Chronic heart failure is a disease with growing importance in modern cardiology. In spite of a significant progress the treatment results are still far from satisfactory. Pulmonary hypertension (PH) is a harbinger of poor prognosis in this group of patients increasing the risk of hospitalisation and death. Pulmonary hypertension secondary to left heart diseases is a result of diastolic and systolic dysfunction leading to increased left ventricular filling pressures. That, in turn, is followed by further unfavourable pathophysiological and functional changes in pulmonary circulation ultimately causing right ventricular failure. Diagnosis and treatment of pulmonary hypertension is not an easy task. Thankfully, the development of diagnostic methods, uniformed terminology and a new classification of pulmonary hypertension allow for faster and more precise diagnosis and qualification of patients to the appropriate clinical subgroup. Right heart catheterization is crucial for the final diagnosis and classification of pulmonary hypertension. Proper methodology of the examination and drawing appropriate conclusions from available haemodynamic and clinical data is essential for further therapeutic management. Most of targeted therapies are addressed to patients with pulmonary arterial hypertension and the administration of these drugs in PH-LHD was either not sufficiently studied in randomized trials or was proved to cause the harm. There is a distinct need for further research on basic mechanisms of PH-LHD as well as on novel therapeutic strategies that may stimulate the development of new guidelines on the treatment of this growing population of PH patients.

INFLUENCE OF LIPOSUCTION OF LARGE VOLUME ON SYSTEMIC AND LUNG CIRCULATION, OXIGENATED LUNG FUNCTION

The authors measured the changes of hemodynamics in 72 patients. It was also estimated a blood oxygenation and volume of liquid sectors of the organism in different degree of obesity before and after liposuction of the large volume. It was shown, that this operation facilitated to an improvement of respiratory lung function due to changes of pulmonary circulation.

Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge

Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.

Changes in pulmonary circulation of patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis complicated by chronic respiratory failure

The aim of this study was to describe particularities of pulmonary circulation in patients with obstructive (chronic obstructive pulmonary disease (COPD)) or restrictive (idiopathic pulmonary fibrosis (IPF)) diseases and to study tendencies of pulmonary blood flow disorders in different pathological mechanisms of chronic respiratory failure (CRF). Methods . Results of image examination (multislice computed tomography, computed angiography, singlephoton emission computed tomography) were analyzed in 150 patients with severe stage 3–4 COPD (phenotype of emphyse ma) complicated by CRF or right heart failure and in 45 patients with IPF and lung «honeycombing». Results. Significant pulmonary circulation disorders were seen in patients with both obstructive and interstitial diseases complicated by CRF. These changes were caused by parenchyma remodeling, concomitant vascular lesions (pulmonary embolism, thrombosis in situ), cancer and persistent infectious inflammation. Conclusions. Timely detection of changes in pulmonary parenchyma and vessels allows adequate treatment, slowing progression of the disease and improving outcomes. In patients with mild to moderate COPD, therapeutic interventions could improve the reduced blood flow in ischemic areas of the lungs significantly more often than in IPF patients. Early treatment could prevent irreversible change in ischemic lung parenchyma which usually results in CRF development. Virtually, treatment has no effect on pulmonary circulation both in patients with obstructive and restrictive diseases with irreversible changes in pulmonary vessels.

High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension

Background Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P &lt;0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P &lt;0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P &lt;0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P &lt;0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r=0.477-0.589, P &lt;0.05). Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Pathological changes in pulmonary circulation in carbon tetrachloride (CCl4)-induced cirrhotic mice.

RationaleLack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease.ObjectiveWe investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH.Methods And ResultsMale C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery.ConclusionCollectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions.

Clinical study on pulmonary circulation changes in patients with acute respiratory distress syndrome induced by lung contusion

To analyze the variation and significance of pulmonary circulation in patients with acute respiratory distress syndrome (ARDS) induced by lung contusion by means of Swan-Ganz catheter and the pulse index continuous cardiac output (PiCCO) monitoring. A prospective, randomized, non-blinded clinical trial was conducted. All patients admitted hospital from August 2009 to August 2011 met the inclusion criteria, were divided into the group with ARDS induced by lung contusion (contusion group, n = 18) and the group without lung contusion and ARDS (control group, n = 22). The measured parameters included pulmonary artery systolic pressure (PAS), pulmonary artery diastolic pressure (PAD), pulmonary artery wedge pressure (PAWP), pulmonary artery diastolic-pulmonary wedge pressure gradient (PAD-PAWP), and extravascular lung water index (ELWI) of each group at 0 hour after placing the catheter and at 12, 24, 36, 48, 60, 72 hours after contusion. The differences of all the parameters were compared within a group and among the different groups. In the survivors with ARDS induced by lung contusion, PAS, PAD and PAD-PAWP were significantly higher than those in the control group and then gradually declined. PAS and PAD returned to the level of control group at 60 hours after contusion, and the PAD-PAWP restored to the level of control group at 48 hours after contusion. For the patients in the control group, there were no significant differences in PAS and PAD from the 0 hour after placing catheter to 72 hours after contusion, but PAD-PAWP increased at 72 hours after contusion compared with at 48 hours. Compared with the control group, the ELWI in contusion group increased significantly, and peaked at 12 hours after contusion and then gradually declined, and restored to the level of control group at 60 hours after contusion. For the patients in the control group, ELWI were lower at 60 hours and 72 hours after contusion than at 48 hours. Compared with control group, PAWP in contusion group decreased at 0 hour, and returned to the level of control group at 48 hours after contusion. For the patients in the control group, there were no significant differences in PAWP from the 0 hour after placing the catheter to 72 hours after contusion. The positive correlation were found between ELWI and PAS, PAD, PAD-PAWP from 0 hour after placing the catheter to 48 hours after contusion in contusion group (r value, 0.554, 0.498, 0.629, respectively, all P < 0.01). Among the patients with ARDS induced by lung contusion, it appears that changes in PAS, PAD and PAD-PAWP, as well as ELWI play important roles in assessing fluid status, guiding mechanical ventilation and severity.

Female gender and pulmonary arterial hypertension: a complex relationship

Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as mean pulmonary artery pressure ≥25 mmHg and normal pulmonary capillary wedge pressure (≤15 mmHg). In PAH the increase in pulmonary pressure is due to an intrinsic disease of the small pulmonary arteries (resistance vessels) characterized by vascular proliferation and remodeling. The increase in pulmonary vascular resistance with subsequent elevation of the right ventricular afterload leads to right ventricular failure after variable periods of time. Although targeted disease therapies have been developed over the last decade that resulted in improved quality of life and outcome for PAH patients, the prognosis is still severe and there remains no cure for this disease. From a clinical standpoint, PAH includes a group of heterogeneous pathological conditions: in idiopathic, heritable and drug- and toxin-induced PAH, since there are no predisposing clinical conditions, the structural changes in pulmonary circulation are "isolated"; on the other hand, PAH may be associated with some predisposing diseases such as connective tissue disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can affect individuals of all age groups, and mean age at diagnosis is around 50 years. Epidemiological data show a great preponderance of females in PAH; the high prevalence of females is particularly evident in the so-called "isolated" PAH forms, whereas in PAH associated with other diseases the female:male ratio is strongly influenced by the epidemiological features of the specific predisposing condition. The reason for the higher female prevalence in PAH has never been clarified: some hypotheses involve the role of sexual hormones (estrogens), autoimmunity, or an X-linked locus in disease predisposition. Female gender is not associated with a different clinical presentation. However, the age of onset tends to be earlier in females than in males. As far as prognosis is concerned, male patients are at greater risk of mortality despite similar therapeutic management: this could be linked to the influence of sexual hormones, which may favor disease development but may also have favorable effects on outcome, especially on treatment response (the "estrogen paradox"). The possibility that female sex hormones may influence the development and clinical expression of PAH is underlined by the frequent onset of PAH during pregnancy or shortly after delivery, and by the description of obligate carriers of heritable PAH (BMPR2 mutation carriers) in whom hormone replacement therapy seems to trigger the manifestation of the disease. Nevertheless, a definite pathobiological mechanism to explain the association between female sex hormones and PAH has yet to be identified. The link between pregnancy and PAH is also uncertain. However, the hemodynamic changes that occur during gestation, and mainly during labor and delivery, are poorly tolerated by PAH patients: this is reflected in the timing of clinical deterioration and the increased mortality in the late stages of pregnancy when maximum increase in blood volume and cardiac output occurs. As such, the current clinical recommendation is that pregnancy should strongly be discouraged and if it occurs, early termination is advised. When PAH is not diagnosed until late in pregnancy, close follow-up of the mother is mandatory and elective planned delivery is recommended: care of pregnant women with PAH requires a highly planned, multidisciplinary approach, involving obstetricians, pulmonary hypertension specialists, anesthesiologists and intensivists, preferably in a dedicated PAH referral center. Use of female hormones for birth control and postmenopausal replacement therapy in PAH patients still remains controversial; in fact, although it has been suspected to be a trigger factor for PAH development, a formal association based on case-control studies has not been documented.

Mechanical ventilation can cause changes in pulmonary circulation

Ñamendys-Silva, Silvio A. MD, MSc, FCCP; Domínguez-Cherit, Guillermo MD, FCCM Author Information