Pressure In Pulmonary Circulation Research Articles

Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension.

Hypoxic pulmonary hypertension (HPH) is a complicated vascular disorder characterized by diverse mechanisms that lead to elevated blood pressure in pulmonary circulation. Recent evidence indicates that HPH is not simply a pathological syndrome but is instead a complex lesion of cellular metabolism, inflammation, and proliferation driven by the reprogramming of gene expression patterns. One of the key mechanisms underlying HPH is hypoxia, which drives immune/inflammation to mediate complex vascular homeostasis that collaboratively controls vascular remodeling in the lungs. This is caused by the prolonged infiltration of immune cells and an increase in several pro-inflammatory factors, which ultimately leads to immune dysregulation. Hypoxia has been associated with metabolic reprogramming, immunological dysregulation, and adverse pulmonary vascular remodeling in preclinical studies. Many animal models have been developed to mimic HPH; however, many of them do not accurately represent the human disease state and may not be suitable for testing new therapeutic strategies. The scientific understanding of HPH is rapidly evolving, and recent efforts have focused on understanding the complex interplay among hypoxia, inflammation, and cellular metabolism in the development of this disease. Through continued research and the development of more sophisticated animal models, it is hoped that we will be able to gain a deeper understanding of the underlying mechanisms of HPH and implement more effective therapies for this debilitating disease.

Investigation of Genes and Proteins Expression Associating Serotonin Signaling Pathway in Lung and Pulmonary Artery Tissues of Dogs with Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease: The Preliminary Study.

Simple SummaryPulmonary hypertension is an unusual elevation of the blood pressure in pulmonary circulation. In dogs, pulmonary hypertension is commonly occurred as a complication of progressive degenerative mitral valve disease especially in senior small-breed dogs. Previous studies revealed that the serotonin signaling pathway is associated with the pathogenesis of pulmonary hypertension. However, research in dogs was scarce. Therefore, the present study aimed to illustrate the understanding of this point by assessing the expression of the targeted genes and proteins related to the serotonin pathway in lung tissues and pulmonary arteries of dogs. Our results showed that the pattern of gene and protein expression was different in canine lung and pulmonary arteries. The targeted proteins in pulmonary artery tissues of the degenerative mitral valve disease dogs with and without pulmonary hypertension tended to be upregulated. In addition, the expression of these protein was increased in the pneumocytes of the alveolar walls, pulmonary alveolar macrophages, and bronchial epithelial cells. A correlation between the targeted gene and protein expression and the echocardiographic data was also founded. Overall results pointed out that the serotonin pathway in lung and pulmonary artery tissues might have different roles in degenerative mitral disease with and without pulmonary hypertension.Pulmonary hypertension (PH) is defined as an increase in pulmonary vascular pressure. It is one of the most common complications that occur as a result of degenerative mitral valve disease (DMVD) in dogs. Serotonin (5-HT) can trigger the development of PH. Accordingly, this study investigated the changes in the expression of genes and proteins associated with local 5-HT signaling in the lungs and pulmonary arteries (PA) of dogs with PH secondary to DMVD. Lung and PA tissue samples were collected from the cadavers of fourteen small-breed dogs and divided into normal (n = 4), DMVD (n = 5) and DMVD with PH (n = 5) groups. Gene expression (tph1, slc6a4 and htr2a) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of proteins (TPH-1, SERT, 5-HTR2A, ERK1/2 and pERK1/2) was examined by Western blot analysis and immunohistochemical staining. The results showed that the expression of genes and proteins evaluated by qRT-PCR and Western blot analysis in lung and PA tissues did not differ among groups. However, the expression of proteins related to 5-HT signaling tended to be upregulated in PA tissues from DMVD dogs with and without PH. Immunohistochemical examination revealed the overexpression of these proteins in the DMVD and DMVD with PH groups in lung tissue. These findings suggest a local effect of 5-HT signaling in DMVD dogs with and without PH.

Some Unanticipated Consequences of Early Cardiac Catheterization. Insights into Pulmonary Pathophysiology.

One of the most interesting unanticipated findings by André Cournand and Dickinson Richards in their groundbreaking studies of cardiac catheterization was the very low pressure in the normal pulmonary circulation. At the time, in the 1940s, the significance of this was not appreciated. For example, in their speeches at the Nobel Prize ceremony, neither of these laureates referred to the low pressure, although they did discuss other features of the pulmonary circulation. It was up to the cardiologist, William Dock, to point out that these low pressures implied a very uneven distribution of blood flow in the lung, and in particular that in the normal upright lung, the blood flow to the apex would be extremely small. Dock went on to argue that this low blood flow at the top of the lung was responsible for the characteristic apical distribution of adult pulmonary tuberculosis. Since that time, it has been recognized that the low pressures in the pulmonary circulation have many implications in pulmonary pathophysiology. For example, if the vascular pressure is further reduced, such as in hemorrhagic shock, gas exchange is seriously affected because of the development of a large alveolar dead space. Furthermore, if humans are subjected to increased acceleration, such as in a high-performance aircraft, the distribution of blood flow becomes extremely abnormal, with much of the lung being completely unperfused. There are also diseases where distribution in the lung is affected by the uneven distribution of blood flow. These include alpha-1 antitrypsin deficiency and metastatic calcification of the lung.

Experts consensus on the management of the right heart function in critically ill patients

Experts consensus on the management of the right heart function in critically ill patients

EFFECT OF OXACOM ON THE RIGHT VENTRICULAR PRESSURE IN RATS WITH MONOСROTALIN-INDUCED PULMONARY ARTERIAL HYPERTENSION

Background. Pulmonary arterial hypertension (PAH) is a relatively rare disease, but its therapy is expensive and effectiveness is moderate. One of important mechanisms of PAH pathogenesis is reduced formation of nitric oxide in pulmonary vascular endotheliocytes. Objective . To study the effect of oxacom (dinitrosyle iron complex with ligand glutathione), which already demonstrated long-term decline in blood pressure (BP) in systemic circulation, on pressure in pulmonary circulation. Design and method . To induce PAH, the standard monocrotalin rat model was used. Three weeks after monocrotalin introduction (60 mg/kg), a catheterization of the right ventricle was performed in anesthetized rats (100 mg/kg ketamine) through jugular vein and pressure was measured. Simultaneously, BP in femoral artery and ECG were recorded. Results . Systolic pressure in the right ventricle (SPRV) in rats after monocrotalin introduction doubled compared with the control group, from 35 to 70 mmHg, but myocardial contractility index fell by 28 %, also duration of QRS complex and the height of T-wave increased. Intravenous oxacom (40 mg/kg) quickly reduced SPRV by average of 12 ± 3 mmHg, and this level was maintained for an hour. This effect was absent in control rats. Similar BP changes in systemic circulation were observed in both groups. Inhalation of nitric oxide led to BP decrease only in animals with high level of SPRV. Inhalation of oxacom was ineffective. Conclusion . Oxacom is a promising substance for sustained pressure decline in the pulmonary circulation in PAH, but further investigations are needed for the development of a more suitable prolonged-action form of the drug.

Progress of pediatric pulmonary hypertension associated with respiratory diseases

Pulmonary hypertension is a group of diseases with high pressure of pulmonary circulation, severe cases can lead to increased right ventricular afterload, even right heart failure.Children pulmonary hypertension is difficult to detect in early stage because its nonspecific clinical manifestations.It is a serious complication of many respiratory diseases, it leads to decreased lung function and life quality.Screening early pulmonary hypertension of these children will facilitate it's diagnosis, treatment and prognosis. Key words: Pulmonary hypertension; Pulmonary arterial hypertension; Respiratory system; Children

Pulmonary Hypertension: How the Radiologist Can Help

Pulmonary hypertension is defined as an abnormal elevation of pressure in pulmonary circulation, with a mean pulmonary arterial pressure higher than 25 mmHg, regardless of the underlying mechanism. The clinical classification system for pulmonary hypertension was updated at the fourth World Symposium on Pulmonary Hypertension in Dana Point, California, in 2008. In patients with suspected pulmonary hypertension, the diagnostic approach includes four stages: suspicion, detection, classification, and functional evaluation. It is crucial to understand the advantages and disadvantages of the different imaging tools available for the diagnostic work-up and follow-up of patients with pulmonary hypertension. Many conditions that cause pulmonary hypertension have suggestive findings at multidetector computed tomography or magnetic resonance imaging; some causes may be surgically treatable, whereas others may demonstrate adverse reactions to vasodilator therapies used during the course of treatment. Therefore, the radiologist plays an important role in evaluating patients with this disease. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.321105232/-/DC1.

Hypoalbuminemia and Length of Mechanical Ventilation in ARDS

PURPOSE: Acute respiratory distress syndrome (ARDS) is a potentially fatal disease process. The main mechanism of morbidity and mortality is hypoxia and multi-organ failure. There is need for markers that may help earlier diagnosis and predict clinical outcomes. Low albumin causes decreased oncotic pressure in pulmonary circulation leading to more extravasation of fluid into alveoli. There have been few studies showing higher risk of developing ARDS in hypo-proteinemia. The purpose of this study is to determine if there is an association of hypoalbuminemia with length of mechanical ventilation in ARDS.

RV AND LY DYNAMICS DURING DIRECT MECHANICAL VENTRICULAR ACTUATION OF THE FAILING HEART

Purpose of study: Direct Mechanical Ventricular Actuation (DMVA) is a non-blood contacting, vaccum attached, pneumatically regulated biventricular, systolic and diastolic assist device. Its effectiveness has already been demonstrated clinically when applied to the fibrillating heart. This study assesses DMVA's effect on left and right ventricular dynamics when applied to biventricular failure state. Methods: After general anesthesia 10 bovine (113±8kg) underwent left thoracotomy and were instrumented for continuous hemodynamic monitoring. Cardiac Index <1,5 l/min/m2 was achieved by a β 1 blockade for one hour, while heart rate was maintained at 100 bpm by AV-sequential pacing, before synchronous DMVA support was applied for 3 hours. Results: β1 blockade lead to reduction of Cardiac Index (C1) by 68% and 71% (*p<0,05) of the left and right ventricle respectively. Supported by DMVA CI increased immediately by 203% and 225%* with a maximum of 318% and 348%* respectively. RV versus LV output was elevated by 35% to 45% with RV unloading occuring earlier than LV unloading during DMVA support. Arterial pressures increased significantly*, while pulmonary artery pressures remained unchanged throughout DMVA support period. Elevated central venous pressures during failure returned to baseline during DMVA while left atrial pressures remained relatively unchanged. Conclusion: DMVA supports left and right ventricular function equally. RV unloading occurs prior to the LV during DMVA support as similar compressive forces are applied to both ventricular chambers. Lower pressures in pulmonary circulation, therefore, lead to a distinct separtion in peak pulmonary and systemic pressures. Pulmonary congestion is effectively avoided by ensuring complete LV assist.

Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension

Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation.

Quantitative analysis of pulmonary vascular disease in complete transposition of the great arteries.

Forty autopsy cases of complete transposition of the great arteries (TGA) and 22 autopsy cases of ventricular septal defect (VSD) were analyzed histologically for evidence of vascular damage due to pulmonary vascular disease (PVD). Positive correlations were generally observed between an index of pulmonary vascular disease (IPVD) and blood pressure of pulmonary circulation. No significant difference in IPVD was found between TGA and VSD in the first five months of life, when cases of each disease were compared at similar blood pressure levels. After that age, however, IPVD was much higher in TGA, and particularly severe PVD in this disease was demonstrated histologically. Morphometrical analysis of the pulmonary artery revealed hypertrophy of the muscular cost in response to elevated blood pressure. However, the progress of medial hypertrophy was retarded in TGA in the first five months, and medial thickness in arteries of cases of TGA older than five months was only 70% of that in VSD at the same blood pressure levels. Suppression of this process of reinforcement of the arterial wall in response to the stress of high pulmonary pressure was regarded as one of the important factors precipitating severe pulmonary vascular disease in transposition of the great arteries.

Monocrotaline and the heart: Right ventricular hypertrophy in monocrotaline pyrrole treated rats

Adrenomedullin is a strong vasorelaxing peptide discovered in pheochromocytoma tissue. Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to cause pulmonary hypertension. To test the hypothesis that adrenomedullin plays a role similar to that of atrial natriuretic peptide or brain natriuretic peptide in modulating right ventricular responses to pulmonary hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of monocrotaline treated rats with those of control rats. We also measured the effect of pulmonary hypertension on plasma level of the peptide. The concentrations of adrenomedullin immunoreactivity in right ventricle and plasma were significantly higher in monocrotaline treated rats than in control rats. The messenger RNA level of adrenomedullin in right ventricle was also higher in monocrotaline treated rats than in control rats. These results suggest that adrenomedullin participates in the mechanism to counteract the high blood pressure in pulmonary circulation.

Vertical gradient of perfusion in the erect human lung

A quantitation examination is made of a number of mechanisms which might contribute to the gross nonuniformity of blood flow observed in the erect lung. Passive distension of the small vessels by the increased transmural pressures in the base of the lung is shown to be an insufficient explanation of their heightened blood flow. A vertical assemblage of vascular units operating under “waterfall” conditions shows a rapid change of flow per unit with height. These conditions may be caused to apply over a range of heights near the center of the lung by the assumption of critical closing pressures in the capillary bed. If these pressures are allowed to have a range of values in accordance with the anatomical range of capillary diameters the height-flow relationship is brought close to that observed. The expected behavior of a model of this type is discussed. pulmonary circulation; distensibility of small pulmonary vessels; vertical distribution of pulmonary blood flow; waterfall effect; critical closing pressures in pulmonary circulation Submitted on August 17, 1964