Increase In Pulmonary Arterial Pressure Research Articles

Cardiac Involvment in COVID-19–Related Acute Respiratory Distress Syndrome

The cardiac involvement in Coronavirus disease (COVID-19) is still under evaluation, especially in severe COVID-19-related Acute Respiratory Distress Syndrome (ARDS). The cardiac involvement was assessed by serial troponin levels and echocardiograms in 28 consecutive patients with COVID-19 ARDS consecutively admitted to our Intensive Care Unit from March 1 to March 31. Twenty-eight COVID-19 patients (aged 61.7 ± 10 years, males 79%). The majority was mechanically ventilated (86%) and 4 patients (14%) required veno-venous extracorporeal membrane oxygenation. As of March 31, the Intensive Care Unit mortality rate was 7%, whereas 7 patients were discharged (25%) with a length of stay of 8.2 ±5 days. At echocardiographic assessment on admission, acute core pulmonale was detected in 2 patients who required extracorporeal membrane oxygenation support. Increased systolic arterial pressure was detected in all patients. Increased Troponin T levels were detectable in 11 patients (39%) on admission. At linear regression analysis, troponin T showed a direct relationship with C-reactive Protein (R square: 0.082, F: 5.95, p = 0.017). In conclusions, in COVID-19-related ARDS, increased in Tn levels was common but not associated with alterations in wall motion kinesis, thus suggesting that troponin T elevation is likely to be multifactorial, mainly linked to disease severely (as inferred by the relation between Tn and C-reactive Protein). The increase in systolic pulmonary arterial pressures observed in all patients may be related to hypoxic vasoconstriction. Further studies are needed to confirm our findings in larger cohorts.

Dynamic right and left ventricular interactions in the pig.

What is the central question of this study? Are the mechanisms that cause ventricular interdependence different when due to primary right to left ventricular pressure loading? What is the main finding and its importance? An instantaneous selective increase in aortic pressure causes an immediate increase in right ventricular end-systolic pressure independent of the pericardium, whereas a selective increase in pulmonary artery pressure decreases left ventricular diastolic compliance owing to a subsequent increasing right ventricular end-diastolic volume as a function of an intact pericardium limiting biventricular volume. Changes in contraction synchrony of either ventricle do not appear to be causing these effects. I characterized the dynamic factors determining ventricular interdependence with and without the pericardium. I measured right (RV) and left ventricular (LV) pressures and volumes simultaneously using conductance catheters in seven pentobarbitone-anaesthetized open-chested 5- to 7-week-old piglets. I studied these effects during apnoea, inferior vena caval occlusion and rapid partial aortic and pulmonary arterial occlusions. Conductance catheter-defined long-axis regional volumes were assessed to define regional contractile synchrony. Closed-pericardium measures were made from an initial (baseline) volume, then after two 20mlkg-1 fluid loads followed by an open-pericardium step. Baseline RV and LV volumes were similar. Aortic occlusion increased LV pressures and volumes and RV end-systolic pressure such that RV end-systolic elastance increased without changes in RV contraction synchrony, not affected by the pericardium. Pulmonary artery occlusion increased RV end-systolic pressure but not end-systolic volume. On the subsequent beat, RV end-diastolic pressure increased, whereas LV end-diastolic volume and diastolic compliance decreased. These effects were attenuated by opening the pericardium. Contraction synchrony across longitudinal segments was unaltered by either aortic or pulmonary artery occlusion. I conclude that the determinants of systolic and diastolic ventricular interdependence are different. Increasing RV pressures causes diastolic RV-to-LV interdependence, decreasing LV diastolic compliance and dependent on an intact pericardium. An increase in LV end-systolic pressure increases RV end-systolic elastance independent of the pericardium and has a minimal effect on RV diastolic function or contraction synchrony.

Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies.

Pulmonary arterial hypertension is a rare and devastating disease characterized by an abnormal chronic increase in pulmonary arterial pressure above 20 mmHg at rest, with a poor prognosis if not treated. Currently, there is not a single fully effective therapy, even though a dozen of drugs have been developed in the last decades. Pulmonary arterial hypertension is a multifactorial disease, meaning that several molecular mechanisms are implicated in its pathology. The main molecular pathways regulating the pulmonary vasomotor tone-endothelin, nitric oxide, and prostacyclin-are the most biologically and therapeutically explored to date. However, drugs targeting these pathways have already found their limitations. In the last years, translational research and clinical trials have made a strong effort in suggesting and testing novel therapeutic strategies for this disease. These approaches involve targeting the main molecular pathways with novel drugs, drug repurposing for novel targets, and also using combinatorial therapies. In this review, we summarize current strategies and drugs targeting the endothelin, nitric oxide, and prostacyclin pathways, as well as, the emerging new drugs proposed to cope with vascular remodelling, metabolic switch, perivascular inflammation, epigenetic modifications, estrogen deregulation, serotonin, and other neurohumoral mechanisms characteristic of this disease. Nowadays, pulmonary arterial hypertension remains an incurable disease; however, the incoming new knowledge makes us believe that new promising therapies are coming to the clinical arena soon.

Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship.

Citation:Mesarwi O, Malhotra A. Obstructive sleep apnea and pulmonary hypertension: a bidirectional relationship. J Clin Sleep Med. 2020;16(8):1223–1224.

Egg and banana sign: a radiological sign of severe pulmonary arterial hypertension.

Egg and Banana sign is a novel radiological sign of severe pulmonary arterial hypertension. This sign occurs due to significant increase in pulmonary artery pressures causing increase in size of pulmonary artery and its appearance at the level of aortic arch. Egg and banana sign when used in combination with other clinical and radiological signs, it improves sensitivity and specificity for diagnosis of pulmonary arterial hypertension (PAH). Here we report a case of chronic thromboembolic pulmonary hypertension in a young male with severe PAH causing Egg and Banana sign on axial computed tomography of chest.

Sodium Tanshinone II Sulfonate A Ameliorates Hypoxia-Induced Pulmonary Hypertension.

BackgroundPulmonary hypertension (PH) remains a prevalent disease globally. Sodium tanshinone II sulfonate A (STS) has been used in clinical treatment of PH.AimsThe aim of the present study was to investigate the effect of sodium STS treatment on hypoxia-induced PH and related mechanisms.MethodsMale Sprague-Dawley rats were housed in a hypoxic chamber with an oxygen concentration of 10 ± 1% for 8 h a day over 21 days. Rats were treated with either STS (low-dose: 10 mg/kg or high-dose: 30 mg/kg) or LY294002 (which is an inhibitor of PI3K). Pulmonary arterial pressure (PAP) was measured, right ventricular hypertrophy parameters were monitored, lung edema parameters were measured, and pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions of apoptosis, and PI3K/AKT/mTOR/autophagy pathways in rat lung tissue were examined by western blot. Levels of the pro-inflammatory factors IL-6, IL-8, TNF-α in lung tissues of rats were measured using an enzyme linked immunosorbent assay (ELISA).ResultsResults of our study demonstrate that persistent exposure to hypoxic conditions increased PAP, right ventricular hypertrophy, lung edema, parameters of lung vascular proliferation and decreased the ratio of Bax/Bcl-2. Furthermore, hypoxic conditions activated the PI3K/Akt/mTOR pathway, inhibited autophagy, and elevated abundance of inflammatory factors in rat lung tissue. Treatment with STS resulted in a dose-dependent decrease in PAP, right ventricular hypertrophy, lung edema, lung vascular proliferation and reversed hypoxia induced lung tissue protein expression and pro-inflammatory factors in rat lung tissue. In addition, hypoxia-induced increases in PAP, cardiac hypertrophy, and lung expression of the proteins PI3K/Akt/mTOR/autophagy pathway were partially reversed by treatment with LY294002.ConclusionsSTS alleviates hypoxia-induced PH by promoting apoptosis, inhibiting PI3K/AKT/mTOR pathway, up-regulating autophagy, and inhibiting inflammatory responses.

Pulmonary arterial hypertension in the elderly: Clinical perspectives.

Pulmonary hypertension (PH) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventric-ular failure and death. Pulmonary arterial hypertension (PAH) (World Health Organization Group I), a subset of PH, and may be idiopathic in nature or associated with other systemic conditions and is thought to most commonly effect women, the majority of whom are of childbearing age. However, PAH in the elderly population is being increasingly diagnosed creating clinical considerations that had once not been considered. Often in an elderly population the diagnosis of PAH may be delayed due to chronic comorbid conditions such as coronary artery disease or other dyspneic conditions. Though survival and clinical outcomes have improved, the elderly population continues to have disproportionately lower survival rates. High clinical suspicion of PAH warrants a complete diagnostic workup with right heart catheterization. Upon diagnosis, PAH specific therapy should be initiated with possible drug interactions in mind. Adjuvant pulmonary rehabilitation should be considered as a conservative measure with definitive results. Finally, psychosomatic aspects of the disease should also be considered in elderly populations.

Fatal airway obstruction due to a ball-valve clot with identical signs of tension pneumothorax

Endo-tracheal tube obstruction due to an extensive blood clot is a recognized but very rare complication. A ball-valve obstruction in the airway could function as a check valve for the lung and thorax, resulting in tension pneumothorax-like abnormalities. A 47-year-old female patient had undergone implantation of a left ventricular assist device 3 weeks prior. On post-operative day 17, planned thoracentesis was performed for drainage of a pleural effusion. Despite the drainage, the patient’s oxygenation did not improve, and emergency tracheal intubation was conducted. Subsequent computed tomography revealed bilateral pneumothorax. Two days later, the patient’s trachea was extubated without complication, and a mini-tracheostomy tube was placed. Three hours later, reintubation was conducted due to progressive tachypnea. Although successful intubation was confirmed, ventilation became increasingly difficult and finally impossible. Marked increase in pulmonary artery and central venous pressures suggested progression of the previous tension pneumothorax. After emergency extracorporeal membrane oxygenation was initiated, fiberoptic bronchoscopy revealed the presence of a massive clot and ball-valve obstruction of the endotracheal tube. Two weeks later, the patient died due to severe hypoxic brain damage. Diagnosis of ball valve clot is not simple, but intensivists should consider this rare complication.

Increased Vasoconstriction of the Pulmonary Vasculature in Response to a Hypoxic Challenge in Swine Exposed to Hypoxia in the Neonatal Period

IntroductionAdvances in neonatal care improved the survival of very prematurely born infants. Exposure to high oxygen is often necessary to ensure adequate oxygen uptake in these infants, leading to halted development and oxidative injury of the pulmonary vasculature which is often accompanied by increased pulmonary arterial pressure (PAP). Although pressures normalize in school age childhood, various stressors as hypoxia and exercise may unmask increased pulmonary vasoreactivity. Furthermore, now that these infants reach adulthood, it is increasingly recognized that this large, preterm born adult cohort has a less favorable cardiopulmonary risk profile. Particularly male subjects were shown to respond with a higher increase in PAP upon re‐exposure to hypoxia, which might be a predisposition to pulmonary vascular disease later in life. Pathophysiological risk factors causing this predisposition are unidentified and challenging to investigate in the human population.ObjectiveTo assess if swine with perinatal oxidative injury of the pulmonary vasculature respond differently to re‐exposure to a hypoxic stimulus compared to healthy swine.Methods6 male swine were exposed to 10–12% hypoxia in the neonatal period (NH‐swine) for a maximum of 4 weeks to interfere with normal lung development, while 5 male control pigs (healthy swine) were raised in normoxic conditions. In the NH‐swine, a symptom‐guided method (echocardiographic changes and clinical symptoms) orchestrated timing of the return to normoxic conditions. At the age of 8 weeks, NH and healthy swine were chronically instrumented. In week 10, hemodynamics were evaluated at rest and during exposure to 14–15% oxygen for 20 minutes.ResultsNH‐swine were exposed to a 23±5 days of hypoxia. 2 NH‐swine passed away as a consequence of heart failure before chronic instrumentation. At the age of 10 weeks, baseline PAP (14.6±2 vs 13.8±1 mmHg) and pulmonary vascular resistance (PVR, 4.1±0.7 vs 2.8±0.4 WU) at rest was not different in NH‐swine compared to healthy swine. During the hypoxic challenge, oxygen saturation decreased similarly in both groups compared to baseline measurements. PAP increased upon exposure to hypoxia due to an increase in PVR. The increases in PAP and PVR showed a transient peak after two minutes, which were larger in in NH‐swine compared to healthy swine. PAP and ΔPVR stabilized between 10 and 20 minutes of hypoxia exposure at levels that were not different between groups.ConclusionsInterfering with normal lung development in the first weeks of life induces a transiently exaggerated increase in PAP and PVR during a hypoxic challenge at the age of ten weeks. Normalization of PAP and PVR suggests effective counter mechanisms to reduce cardiac work and increase arterial oxygen saturation. The increased response to hypoxia of the pulmonary circulation suggest long‐term structural and/or functional changes that possibly predisposes the pulmonary circulation to adult pulmonary vascular disease.Support or Funding InformationErasmusMC M‐RACEHypoxic challenge data in 10 week old swine exposed to neonatal hypoxia (NH‐swine) compared to healthy swine. A: Arterial oxygen saturation (sO2), B: Pulmonary arterial pressure (PAP), C: Difference in pulmonary vascular resistance compared to baseline values (ΔPVR). BL ‐ baseline, WU ‐ Wood units. *=p<0.05 between groups, †=p<0.05 compared to baseline valuesFigure 1

GAL3 Regulates Smooth Muscle Cell Survival in PAH via its NWGR Motif

Pulmonary arterial hypertension (PAH) is a complex and fatal disorder characterized by an unrelenting increase in pulmonary arterial pressure. Excessive proliferation of pulmonary artery smooth muscle cells (PASMC) leads to increased vascular resistance and eventually right ventricular failure and death. Our laboratory has identified a key role for Galectin‐3 (GAL‐3 or Lgals3) in driving PASMC proliferation and elevated pulmonary pressures. However, the mechanisms by which GAL‐3 alters PASMC behavior remains poorly understood. GAL‐3 contains a BH1 like domain that has an NWGR sequence with high homology to the anti‐apoptotic protein, BCL2. Our central hypothesis is GAL‐3 upregulation plays an important role in driving PASMC proliferation through repression of apoptosis via the NWGR domain. In order to test the role of this domain we have made an adenoviral vector encoding the GAL‐3 G182A mutation and have shown that it expresses equally to a WT GAL‐3. We have also made a GAL‐3 KO rat and have isolated GAL‐3 PASMCs from these animals (RPASMC). Our in vitro studies show that overexpression of GAL‐3 G182A cause a decrease in viability using flow cytometry upon treatment overnight with 0.5% serum containing media(p<.001). However there was no significant difference in survival(p=.840) when cells were conditioned in normal media. Proliferation experiments similarly showed no significant difference between GAL‐3 WT and G182A in KO human aortic endothelial cells(HAEC) and human PASMC (p>.05). When exposed to apoptotic stimuli (10ng/mL TNFα and 1μg/ml Cycloheximide) GAL‐3 G182A overexpressing GAL‐3 KO RPASMCs had significantly (p<.001) decreased vitality as compared to GAL‐3 WT overexpressing cells. Overall our data suggests that the NWGR domain of GAL‐3 is important in regulating PASMC survivability, and our future work will investigate the role of GAL‐3 mediated apoptosis in animal models of PAH.Support or Funding InformationF31HL147428R01HL125926‐03

A comparison of mitochondrial respiratory function in adult and fetal sheep pulmonary arteries.

Neonatal pulmonary hypertension (PH) occurs in approximately 6/1000 term infants. It results from insufficient vasodilation of the pulmonary arteries at birth, although the underlying etiology is not well understood. This increase in pulmonary arterial pressure can lead to severe systemic hypoxia due to redirection of blood flow away from the lungs via ductus arteriosus, resulting in systemic hypoxia. PH is more common in human fetuses exposed to chronic hypoxia during gestation, a phenomenon that is also demonstrated in our high‐altitude fetal sheep model.There is growing evidence that the mitochondria of pulmonary artery smooth muscle cells (PASMCs) play a key role in establishing vascular tone. Mitochondria are exposed to profound changes in oxygen and substrate availability in the transition from fetus to newborn. To gain a better understanding of the developmental changes in mitochondrial function in PASMCs, we tested the hypothesis that mitochondria from fetal vs adult PASMCs would display different substrate‐dependent rates of oxygen consumption and energy production.Lungs were surgically removed from adult non‐pregnant ewes or near‐term fetuses following greater than 100 days of residing at an altitude of over 3801 meters using protocols approved by the Loma Linda University IACUC. 4th–6th generation intrapulmonary pulmonary arteries were isolated, and denuded of endothelium. The metabolic activity of the arterial segments was analyzed in a Seahorse XFe 24 Analyzer that measures the oxygen consumption rate (OCR) with values being normalized to the arterial segment dry weight. These experiments were conducted in the presence of selective antagonists to enable determination of proton leak, non‐mitochondrial oxygen consumption, basal respiration, ATP‐linked respiration, maximal respiration, and spare capacity.Four adults and six fetuses were studied. Compared to adults, fetal PASMCs demonstrated a greater maximal respiratory capacity [813.99 +/− 73.20 (pmol/min) vs. 601.64 +/− 58.09 (pmol/min)] and spare‐capacity [593.28+/− 48.56 (pmol/min) vs. 353.74 +/− 40.39 (pmol/min)] for oxygen consumption while using carbohydrates and amino acids as substrates (p≤ 0.003, ANOVA). Other parameters of OCR were not different between fetuses and adults.These experiments provide initial evidence that there are maturational changes in mitochondrial function. Ongoing studies are evaluating the contribution of long‐term high altitude exposure to these differences in mitochondrial respiration and their importance to phenotypic and functional aberrations in lung function.Support or Funding Information(Supported in part by NIH grant HD083132 (ABB), HD098477 (SMW))

Glypican‐1 Is a Trigger for Pulmonary Edema Development During Acute Heart Failure

Heart Failure is a growing global epidemic with a prevalence of over 37.7 million cases. Accumulating evidence indicate that the lungs actively participate in the pathogenesis of Heart Failure and, in particular, in the development of pulmonary edema associated with acute heart failure (AHF). The molecular mechanisms by which pulmonary edema develops during AHF are not clarified but increases in pulmonary capillary pressure may play a role. Herein we sought to investigate if glypican‐1 (Gpc1), a heparan sulfate proteoglycan known to be activated by pressure, contributes to hyperpermeability and pulmonary edema during AHF. We hypothesize that Gpc1 induces pulmonary edema via eNOS uncoupling and RhoA nitration. The isolated perfused lung preparation was used to simulate AHF in male CD‐1 (wild type, WT) and glypican‐1 knockout (Gpc1KO) mice (6 weeks old). Control experiments were done setting left atria pressure (PLA) at 3cm H2O for 10 minutes; AHF was simulated by setting PLA at 10 cm H2O for 10 minutes. Lung edema was assessed by lung wet‐to‐dry ratio; heart function was assessed by echocardiography, reactive oxygen species (ROS) production was assessed by lucigenin enhanced chemiluminescence. PKCa activation, eNOS phosphorylation at T495 and Rho nitration were assessed by immunoblotting. An in vitro approach was taken to further investigate the molecular mechanisms by which increased pressure leads to endothelial hyperpermeability: human lung microvascular endothelial cells (HLMEC) were exposed or not to high hydrostatic pressure (30cm H2O) for 10 minutes and analysis of activation of PKC‐eNOS‐RhoA axis was performed by immunoblotting. WT and Gpc1KO mice showed similar ejection fraction and increase in pulmonary artery pressure. Deletion of Gpc1 protected mice from pulmonary edema associated with AHF and prevented increase on ROS production. Inhibition of eNOS with L‐NIO mitigated pulmonary edema during AHF in WT mice. NOC‐9, a NO donor, restored the ability of GPC1KO lungs to develop edema during AHF. Moreover, WT mice showed increased eNOS phosphorylation at T495, PKCa activation and RhoA nitration during AHF, effects not seen in Gpc1KO. In vitro, increased hydrostatic pressure induced activation of the same pathways as seen in the in situ model. Taken together, these results suggest that activation of Gpc1 leads to eNOS uncoupling and RhoA nitration that results in endothelial hyperpermeability and pulmonary edema during AHF. These data evidence the lung endothelium as an active player during AHF and glypican‐1 as a gatekeeper of barrier function.Support or Funding InformationP01 HL134610 (SMB) and funds from the Department of Anesthesiology, College of Medicine, University of Arizona, Tucson and the Department of Anesthesiology, College of Medicine, University of Illinois at Chicago.

Impaired Oxygenation of the Right Ventricle during Development of Pulmonary Hypertension in Swine is not due to Loss of Nitric Oxide

BackgroundPulmonary hypertension (PH) increases workload of the right ventricle (RV), resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood, but we have recently shown that myocardial oxygen supply did not increase commensurate with the increase in myocardial oxygen demand. This mismatch between oxygen supply and demand is exacerbated during physical activity when workload and hence oxygen demand increases. Here, we aim to investigate whether the contribution of the vasodilator nitric oxide (NO) and/or the vasoconstrictor endothelin (ET) to regulation of right ventricular coronary blood flow (RV‐CBF) is impaired in swine with PH.MethodsPH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (RV‐CBF) rest and during graded treadmill exercise. Exercise was performed in the presence and absence of eNOS‐inhibition or ET‐receptor blockade 12 weeks after pulmonary vein banding (PVB).ResultsPVB resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 39±3 mmHg, CON: 21±1 mmHg, both P<0.05) that was accompanied by RV hypertrophy (Fulton index PVB: 0.58±0.02, CON: 0.44±0.02, P<0.05). The relation between myocardial oxygen supply (RV‐CBF*arterial oxygen content) and myocardial work (arterial elastance, pulmonary artery pressure/SV) rotated downward in PVB. However, despite increased plasma ET‐levels (PVB:8.8±0.5 pg/ml CON: 6.7±0.5 pg/ml, P<0.05), ET‐receptor blockade did not alter the relation between myocardial oxygen delivery and myocardial work. Conversely, eNOS‐inhibition resulted in a downward rotation of this relation that was more pronounced in PVB as compared to CON.ConclusionPH leads to a mismatch between myocardial oxygen supply and demand. This mismatch is not influenced by ET‐receptor blockade and is aggravated by eNOS‐inhibition, suggesting that NO plays an important role in maintaining RV‐perfusion particularly during exercise.

Terlipressin Increases Systemic and Lowers Pulmonary Arterial Pressure in Experimental Acute Pulmonary Embolism.

We investigated whether the vasopressin-analog, terlipressin induces systemic vasoconstriction and pulmonary vasodilation in a porcine model of acute pulmonary embolism. Controlled, animal study. Tertiary medical center research laboratory. Female pigs (n = 12, Cross of Land Race, Duroc, and Yorkshire ~ 60 kg). Acute pulmonary embolism was induced by administration of three large autologous emboli. Animals then received four increasing doses of either terlipressin (n = 6) or vehicle (n = 6). Effects were evaluated in vivo at baseline, after pulmonary embolism and after each dose by invasive hemodynamic measures, transesophageal echocardiography, and blood analysis. Isolated pulmonary arteries were evaluated ex vivo in a myograph. Pulmonary embolism caused a four-fold increase in pulmonary vascular resistance (p < 0.0001) and a two-fold increase in mean pulmonary arterial pressure (p < 0.0001) compared with baseline. Terlipressin increased mean systemic blood pressure (28 ± 5 mm Hg; p < 0.0001) and systemic vascular resistance (1,320 ± 143 dynes; p < 0.0001) compared with vehicle. In the pulmonary circulation, terlipressin decreased mean pulmonary arterial pressure (-6.5 ± 1.8 mm Hg; p = 0.005) and tended to decrease pulmonary vascular resistance (-83 ± 33 dynes; p = 0.07). Terlipressin decreased cardiac output (-2.5 ± 0.5 L/min; p < 0.0001) and increased plasma lactate (2.7 ± 0.2 mmol/L; p < 0.0001), possibly indicating systemic hypoperfusion. A biomarker of cerebral ischemia, S100b, remained unchanged, suggesting preserved cerebral perfusion (0.17 ± 0.11 µg/L; p = 0.51). Ex vivo, terlipressin relaxed pulmonary and constricted mesenteric arteries. Terlipressin caused systemic vasoconstriction and pulmonary vasodilation in a porcine in vivo model of acute pulmonary embolism and vasorelaxation in isolated pulmonary arteries. Despite positive vascular effects, cardiac output declined and plasma lactate increased probably due to a predominantly systemic vasoconstrictor effect of terlipressin. These findings should warrant careful translation to the clinical setting and does not suggest routine use in acute pulmonary embolism.

Mechanosensitive Mechanism of Lung Regeneration through Endothelial YAP1

Angiogenesis, the formation of new blood capillaries, plays a key role in organ development, homeostasis and regeneration. In addition to chemical factors, mechanical forces control angiogenesis and organ regeneration. We have reported that the mechanosensitive transcriptional co‐activator Yes‐associated protein (YAP1) in endothelial cells (ECs) is necessary for post‐pneumonectomy (PNX) lung growth. Right pulmonary artery (PA) pressure and shear stress increase after left unilateral PNX. However, it remains unknown whether changes in PA pressure and shear stress after PNX control post‐PNX regenerative lung growth through endothelial YAP1 signaling. Here we found that ligation of the right cardiac lobe PA after left PNX further increases right PA pressure and shear stress, upregulates expression of YAP1 and angiogenic factor Tie2, and stimulates post‐PNX lung growth in the remaining non‐occluded lobes. These effects are attenuated in VE‐cadherin‐specific Yap1 knockout mice. Hydrostatic pressure or shear stress applied to cultured human pulmonary arterial ECs also increases the expression and activity of YAP1 and induces EC proliferation and migration in vitro. These results suggest that increases in the right PA pressure together with elevation in shear stress after left PNX stimulate angiogenesis and post‐PNX lung growth through endothelial YAP1. Modulation of the mechanical environment or endothelial YAP1 expression/activity could be an efficient strategy for regenerative lung growth.Support or Funding InformationNIH RO1HL142578

Stretching our understanding of baroreflex control in humans: evidence of a positive feedback pulmonary baroreflex.

Stretching our understanding of baroreflex control in humans: evidence of a positive feedback pulmonary baroreflex.

Socio-economic burden of pulmonary hypertension: relevance of assessment in Russia and the world

Pulmonary hypertension (PH) is a progressive disease which is characterized with the increase of pulmonary artery pressure and pulmonary vascular resistance. Such condition leads to right ventricular heart failure and premature death of patients. Pulmonary arterial hypertension (PAH) has the status of an orphan disease. However in Russia only idiopathic PH is included in the list of 24 life-threatening and chronic progressive rare diseases, while other forms of PH are not in it. Inclusion in this list guarantees drug provision for patients at the expense of the regional budget, while patients with other forms of PH can rely on free medication only if they have a disability. The lack of criteria for revising this list as well as the imperfection of legal regulation in the field of drug support for orphan diseases leads to high disability, a significant decrease in the duration and quality of life of patients with PH. As part of a multicriteria approach, a clinical and economic analysis of the disease burden can be one of the tools for policy development and decision-making on the distribution of funding in the healthcare. The article provides a review of the economic burden of various forms of PH in the world.

Exercise intolerance in heart failure: The important role of pulmonary hypertension

What is the topic of this review? This review concerns the negative impact of pulmonary hypertension (PH) on the pulmonary haemodynamic and gas exchange responses to exercise, considering the mechanisms by which PH plays a role in exercise intolerance in heart failure (HF) patients. What advances does it highlight? The hallmark limited pulmonary vascular 'reserve' and impaired pulmonary gas exchange responses to exercise in HF are worsened by the development of PH; these are key determinants of exercise intolerance. Even HF patients who present with 'normal' pulmonary vascular function experience exercise-induced PH, which plays a role in exercise intolerance. Patients with heart failure universally complain of exertional intolerance, but the underlying cause(s) of this intolerance may differ between patients with different disease phenotypes. Exercise introduces an impressive stress to the lungs, where elevations in venous return and cardiac output engender substantial increases in pulmonary blood volume and flow. Relative to healthy individuals, the pulmonary vascular reserve to accept this increase in pulmonary perfusion is compromised in heart failure, with a growing body of evidence suggesting that the development of pulmonary hypertension (PH), and in particular a precapillary component of PH, worsens the pulmonary haemodynamic response to exercise in these patients. Characterized by an exaggerated increase in pulmonary arterial pressure and an elevation in pulmonary vascular resistance, this dysfunctional pulmonary haemodynamic response plays a role in exercise intolerance, probably through an impairment of right ventricular function, underperfusion of the pulmonary circulation and a subsequent reduction in systemic blood flow and oxygen delivery. The hallmark abnormalities in ventilatory and pulmonary gas exchange that accompany heart failure, including a greater ventilatory equivalent for carbon dioxide, are also worsened by the development of PH. This raises the possibility that measures of exercise pulmonary gas exchange might help to 'describe' underlying PH in heart failure; however, several fundamental issues and questions need to be addressed before such gas exchange measures could truly be considered efficacious measures used to differentiate the type of PH and track the severity of PH in heart failure. exercise intolerance, heart failure, pulmonary gas exchange, pulmonary haemodynamics, pulmonary hypertension.

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.

Role Of Inhaled Nitric Oxides In Pregnancy With Eisenmenger Syndrome

ABSTRACTEisenmenger Syndrome (ES) is congenital heart disease with pulmonary hypertension and shunting turning from right to left. The resistance of pulmonary vascular more than 7.5 mmHg/L/min. The right ventricle and pulmonary artery always enlarge. During pregnancy, there will be hemodynamic changes that will affect the ES. It can be understood the possible dangers that can occur, like right heart failure; an increase in pulmonary arteries or the aggravation of pulmonary hypertension because there is no decrease in pulmonary resistance; A sudden decrease in venous return in supine hypotension syndrome can cause a relative increase in pulmonary arterial pressure so as to aggravate pulmonary hypertension and reverse shunting.Physiological effects of inhaled nitric oxide (INO) therapy cause selective pulmonary vasodilation: Hypoxia alveoli causes reversible vasoconstriction, thereby increasing pulmonary wedge pressure. INO can lower it. Moderate cardiac output and systematic arterial pressure are not affected; Selective in pulmonary because it is activated by hemoglobin; Selective vasodilation in the ventilated area, local hypoxia alveoli constricts the surrounding vascular tissue and redistributes blood flow to the ventilated lungs better and higher intraalveolar oxygen pressure. INO enhances this mechanism by increasing blood flow through a well-ventilated lung; Bronchodilators; Pulmonary surfactant, The combination of high concentrations of inspired oxygen and high concentrations of INO reduces the minimum surfactant surface tension.Keywords: Inhalation Nitric Oxides, Pregnancy, Eisenmenger Syndrome