Relevance Of Pulmonary Hypertension Research Articles

Autonomic control of the pulmonary circulation: Implications for pulmonary hypertension.

The autonomic regulation of the pulmonary vasculature has been under-appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension.

Risk assessment in pulmonary hypertension based on routinely measured laboratory parameters

γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center. GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p < 0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort. GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

Extracellular Vesicle TGF-β1 Is Linked to Cardiopulmonary Dysfunction in Human Immunodeficiency Virus.

Extracellular vesicles (EVs) have emerged as important mediators in cell-cell communication; however, their relevance in pulmonary hypertension (PH) secondary to human immunodeficiency virus (HIV) infection is yet to be explored. Considering that circulating monocytes are the source of the increased number of perivascular macrophages surrounding the remodeled vessels in PH, this study aimed to identify the role of circulating small EVs and EVs released by HIV-infected human monocyte-derived macrophages in the development of PH. We report significantly higher numbers of plasma-derived EVs carrying higher levels of TGF-β1 (transforming growth factor-β1) in HIV-positive individuals with PH compared with individuals without PH. Importantly, levels of these TGF-β1-loaded, plasma-derived EVs correlated with pulmonary arterial systolic pressures and CD4 counts but did not correlate with the Dl CO or viral load. Correspondingly, enhanced TGF-β1-dependent pulmonary endothelial injury and smooth muscle hyperplasia were observed. HIV-1 infection of monocyte-derived macrophages in the presence of cocaine resulted in an increased number of TGF-β1-high EVs, and intravenous injection of these EVs in rats led to increased right ventricle systolic pressure accompanied by myocardial injury and increased levels of serum ET-1 (endothelin-1), TNF-α, and cardiac troponin-I. Conversely, pretreatment of rats with TGF-β receptor 1 inhibitor prevented these EV-mediated changes. Findings define the ability of macrophage-derived small EVs to cause pulmonary vascular modeling and PH via modulation of TGF-β signaling and suggest clinical implications of circulating TGF-β-high EVs as a potential biomarker of HIV-associated PH.

Smooth Muscle Cells: A Novel Site of P-Selectin Expression with Pathophysiological and Therapeutic Relevance in Pulmonary Hypertension.

Smooth Muscle Cells: A Novel Site of P-Selectin Expression with Pathophysiological and Therapeutic Relevance in Pulmonary Hypertension.

Study of the changing of right atrial volume and phasic function and its clinical value in patients with pulmonary hypertension

Objective To evaluate the right atrial(RA) volume and phasic function using three-dimensional echocardiography(3DE), and to examine the clinical relevance in pulmonary hypertension(PH). Methods Fifty PH patients and 20 control subjects were studied.RA volume, including maximum RA volume (Vmax), minimum RA volume (Vmin) and the volume before active systolic (Vpre-A) were evaluated by 3DE. RA maximum volume index (VmaxI), total emptying volume index (TotEVI), passive emptying volume index (PassEVI) and active ejection fraction (ActEF) were calculated. The correlation between RAVmaxI and the parameters of RV structure, function, pulmonary hemodynamics were analyzed. Results Maximum RA volume index (RAVmaxI) was higher in WHO functional class (WHO-FC) Ⅲ, Ⅳ of PH patients than in controls (all P<0.01). TotEVI was significantly higher in PH patients than in controls (P<0.001), but PassEVI was lower in PH patients than in controls (P=0.011). ActEF was similar when comparing PH patients of WHO-FC Ⅱ with controls.ActEF increased in PH patients with WHO-FC Ⅲ as compared with controls (P=0.008) but reduced in advanced with WHO-FC Ⅳ patients (P<0.001). RAVmaxI correlated with the indices of right ventricular (RV) structure, function and RV cardiac output index (all P<0.05). Conclusions PH is associated with increased RA size, increased TotEVI, and decreased PassEVI. ActEF increases in PH patients with WHO-FC Ⅲ but decreases in patients with WHO-FCⅣ.RA systolic function plays an important role in compensating RV dysfunction. Key words: Echocardiography, three-dimensional; Hypertension, pulmonary; Atrial function, right

Precapillary Oxygenation Contributes Relevantly to Gas Exchange in the Intact Lung

Oxygen uptake is the elemental function of the lung. However, current understanding of this process has largely been derived from theoretical considerations and measurements of global pulmonary gas exchange. To report the direct visualization of pulmonary oxygen uptake in vivo and its use for the analysis of temporal and spatial oxygenation profiles along individual arteriovenous pathways in lungs of healthy and chronic hypoxic mice. A murine model for intravital microscopy of the breathing lung under sealed thorax conditions was combined with multispectral oximetry for two-dimensional oxygen saturation mapping. This combination allowed for visualization of the blood oxygenation process from pulmonary arterioles to capillaries and venules in two-dimensional oxygen saturation maps. Temporal and spatial oxygenation profiles revealed that oxygenation occurs within 100 milliseconds over a distance of approximately 130 μm in the pulmonary microvasculature of the anesthetized mouse. About 50% of total oxygen uptake takes place in precapillary arterioles of less than 30 μm in diameter before the blood enters the alveolar capillary bed. In chronic hypoxic mice, precapillary oxygenation was significantly attenuated as a result of the widened transarteriolar diffusion distance. Oxygen saturation mapping in the intact lung yields unique insights into the temporal and spatial characteristics of pulmonary gas exchange in intact and diseased lungs. Precapillary gas exchange contributes importantly to blood oxygenation at rest, but is attenuated in remodeled lung arterioles, which may be of relevance in pulmonary hypertension.

Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists.

For decades the pulmonary circulation was not considered as important as the systemic (“greater”) circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in un