Increase In Pulmonary Arterial Pressure Research Articles

Management of patients with pulmonary arterial hypertension against of systemic sclerodermia (part 1).

Pulmonary arterial hypertension (PAH) is a serious condition caused by the damage to the small pulmonary vessels, leading to the increase of pulmonary artery pressure, pulmonary vascular resistance, development of right ventricular failure and death. PAH is one of the actual problems of modern medicine due to low survival rate, rapid disability of the patients and a high cost of treatment. PAH is one of the leading causes of death in systemic scleroderma (SSD). PAH associated with scleroderma is a unique phenotype combining the manifestations of both SSD and PAH, the pathogenetic mechanisms of which modify the clinical picture and the course of these conditions. Timely diagnosis and treatment of PAH show significant effect on survival rates, however, early detection of PAH is still difficult in SSD due to several factors. The main causes are restriction of modern screening methods and polyorganic involvement in SSD. In comparison with other subgroups of PAH the patients with SSD-PAH poorly answer to the specific PAH therapy. SSD-PAH, along with idiopathic pulmonary hypertension (IPAH), belongs to group I of pulmonary hypertension classification and according to modern consensus has a similar pathogenesis and clinical picture, however, differences in the response to therapy in these groups are observed, that indicates the role of other pathobiological mechanisms. Recent investigations explain these differences by such factors as autoimmune and inflammatory responses, more severe vascular remodeling and direct myocardial damage in the SSD. Drug therapy of PH in SSD is similar to that in IPAH and includes prostaglandins, endothelin receptor antagonists, calcium channel blockers, which are prescribed in cases of a positive vasoreactive test, PDE-5 inhibitors. In this literature review we showed traditional and new methods of PAH treatment and their relevance to SSD-PAH in accordance with randomized clinical trials.

Nocturnal Hypoxemia, But Not Sleep Apnea, Is Associated With a Poor Prognosis in Patients With Pulmonary Arterial Hypertension

Sleep apnea (SA) can cause repeated nocturnal arterial oxygen desaturation and result in acute increase in pulmonary arterial pressure (PAP). The presence of SA is associated with a poor prognosis in patients with chronic left-sided heart failure, but little is known for patients with pulmonary arterial hypertension (PAH). Methods and Results: We enrolled 151 patients with PAH (44±16 years old, male/female=37/114). They were all in the Nice Classification group 1 (idiopathic PAH/associated PAH=52/48%, mean PAP of 46±16 mmHg). They underwent right-heart catheterization and a sleep study with simplified polysomnography. Averaged percutaneous oxygen saturation (SpO2) during sleep was measured and an apnea-hypopnea index >5 was defined as SA. SA was noted in 58 patients (obstructive SA/central SA: 29/29). Over an average follow-up of 1,170±763 days, 32 patients died. By Kaplan-Meier analysis, there was no significant difference in deaths of patients with and without SA (χ2=2.82, P=0.093). On the other hand, the mortality in patients with lower averaged SpO2 was significantly higher than in those with higher averaged SpO2 (χ2=14.7, P<0.001) and that was the only independent variable related to death in multivariate Cox proportional hazards analysis. SA in patients with PAH was not associated with worse prognosis, unlike left ventricular heart failure, but nocturnal hypoxemia was related to poor prognosis.

Pressure-dependent NOS activation contributes to endothelial hyperpermeability in a model of acute heart failure

Aims: Acute increases in left ventricular end diastolic pressure (LVEDP) can induce pulmonary edema (PE). The mechanism(s) for this rapid onset edema may involve more than just increased fluid filtration. Lung endothelial cell permeability is regulated by pressure-dependent activation of nitric oxide synthase (NOS). Herein, we demonstrate that pressure-dependent NOS activation contributes to vascular failure and PE in a model of acute heart failure (AHF) caused by hypertension.Methods and results: Male Sprague–Dawley rats were anesthetized and mechanically ventilated. Acute hypertension was induced by norepinephrine (NE) infusion and resulted in an increase in LVEDP and pulmonary artery pressure (Ppa) that were associated with a rapid fall in PaO2, and increases in lung wet/dry ratio and injury scores. Heart failure (HF) lungs showed increased nitrotyrosine content and ROS levels. L-NAME pretreatment mitigated the development of PE and reduced lung ROS concentrations to sham levels. Apocynin (Apo) pretreatment inhibited PE. Addition of tetrahydrobiopterin (BH4) to AHF rats lung lysates and pretreatment of AHF rats with folic acid (FA) prevented ROS production indicating endothelial NOS (eNOS) uncoupling.Conclusion: Pressure-dependent NOS activation leads to acute endothelial hyperpermeability and rapid PE by an increase in NO and ROS in a model of AHF. Acute increases in pulmonary vascular pressure, without NOS activation, was insufficient to cause significant PE. These results suggest a clinically relevant role of endothelial mechanotransduction in the pathogenesis of AHF and further highlights the concept of active barrier failure in AHF. Therapies targetting the prevention or reversal of endothelial hyperpermeability may be a novel therapeutic strategy in AHF.

Impairment of left atrial mechanics does not contribute to the reduction in stroke volume after active ascent to 4559m.

Hypoxia challenges left ventricular (LV) function due to reduced energy supply. Conflicting results exist whether high‐altitude exposure impairs LV diastolic function and thus contributes to the high altitude‐induced increase in systolic pulmonary artery pressure (sPAP) and reduction in stroke volume (SV). This study aimed to assess LV diastolic function, LV end‐diastolic pressure (LVEDP), and LA mechanics using comprehensive echocardiographic imaging in healthy volunteers at 4559 m. Fifty subjects performed rapid (<20 hours) and active ascent from 1130 m to 4559 m (high). All participants underwent echocardiography during baseline examination at 424 m (low) as well as 7, 20 and 44 hours after arrival at high altitude. Heart rate (HR), sPAP, and comprehensive volumetric‐ and Doppler‐ as well as speckle tracking‐derived LA strain parameters were obtained to assess LV diastolic function, LA mechanics, and LVEDP in a multiparametric approach. Data for final analyses were available in 46 subjects. HR (low: 64 ± 11 vs high: 79 ± 14 beats/min, P < 0.001) and sPAP (low: 24.4 ± 3.8 vs high: 38.5 ± 8.2 mm Hg, P < 0.001) increased following ascent and remained elevated at high altitude. Stroke volume (low: 64.5 ± 15.0 vs high: 58.1 ± 16.4 mL, P < 0.001) and EDV decreased following ascent and remained decreased at high altitude due to decreased LV passive filling volume, whereas LA mechanics were preserved. There was no case of LV diastolic dysfunction or increased LVEDP estimates. In summary, this study shows that rapid and active ascent of healthy individuals to 4559 m impairs passive filling and SV of the LV. These alterations were not related to changes in LV and LA mechanics.

Right and Left Heart Function in Lowlanders with COPD at Altitude: Data from a Randomized Study

Background: Changes in pulmonary hemodynamics and cardiac function in patients with chronic obstructive pulmonary disease (COPD) traveling to altitude have not been assessed despite an increasing prevalence of the disease. Objectives: We hypothesized that pulmonary artery pressure (PAP) significantly increases and cardiac function deteriorates during exposure to hypobaric hypoxia as encountered by traveling to moderate altitude or air flight. Methods: A total of 37 patients (17 female; median age [quartiles] 66 years [60; 69] with COPD GOLD grade 2–3 [FEV₁ 57% predicted (49; 71)]) living < 800 m underwent echocardiography in Zurich (490 m) and after 1 night at Davos Jakobshorn (2,590 m) in a randomized order of allocation. Results: The transtricuspid pressure gradient increased from 23 mm Hg (18; 29) to 32 mm Hg (25; 41) (p < 0.0001; Δmedian [95% CI] 7.5 [2.0; 13.0]), the right ventricular fractional area change decreased from 45% (39; 49) to 38% (33; 43) (p = 0.002), while the heart rate and systolic blood pressure increased from 70 bpm (64; 78) to 82 bpm (70; 86) (p < 0.0001) and from 133 mm Hg (123; 141) to 136 mm Hg (126; 148) (p = 0.002), respectively, and left ventricular diastolic dysfunction was more prevalent (24–54%, p = 0.02). Conclusions: This is a first study assessing changes in pulmonary hemodynamics and cardiac function in patients with COPD during a short altitude sojourn. Despite the increase in PAP and indications of change in cardiac function, the exposure was well tolerated. None of the patients had to descend to lower altitude for symptomatic altitude-related disease.

Pulmonary hypertension: the state of the art

Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure of 25 mmHg or more at rest assessed by right heart catheterisation. It is a progressive disease characterized by high mortality and morbidity. Current PH guidelines suggest that patients with PH should be cared for in dedicated specialist centres, with expertise and resources available to provide high quality care to this fragile population. In this review, we focus on the clinical manifestations, diagnostic algorithm, risk assessment and therapeutic strategies for PH. We also provide an overview of the organisation of PH services in United Kingdom, including designation of expert centres, national audit and steps to ensure the quality and financial viability of PH care.

Clinical study of patients with primary pulmonary hypertension (PPH)

Background: Pulmonary hypertension (PH) is a hemodynamic and pathophysiological conditiondefined as an increase in mean pulmonary arterial pressure (PAP) ≥25 mmHg at rest as assessed byright heart catheterization (RHC). Although there is some underestimation and overestimation of PAPbetween transthoracic Doppler echo (DE) and RHC, Doppler echo remains an indispensable screeningtool for the assessment of PH.Objective: clinical evaluation of patients with primary pulmonary hypertension (PPH) and assessvasoreactivity testing to identify patients who may benefit from long term therapy with calcium channelblockers (CCBs).Patients and methods: This prospective study was performed in the cardiac catheterization division inAl-Zahraa teaching hospital in Al-Kut. We studied the prevalence of certain variables among forty twopatients with PPH from "March 2014 to Nov 2016" including the clinical triggers, electrocardiographic(ECG) changes, Echocardiographic variables , RHC and vasoreactivity test with intravenous adenosineto identify acute positive responders and long term responders to CCB.Results: A total of forty two patients, female to male ratio were 2.8:1 with a mean age of 38±10(years).Dyspnea is a common clinical trigger (85%). Abnormal ECG was found in (90.5%) of patients, themajority had right ventricular hypertrophy (RVH) (76.2%). Echocardiographically all patients hadRVH. There was some differences in mean PAP (36±4.9mmhg) derived by DE from that obtained byRHC (47±4.78mmhg). RHC reveal that 6 patients (15.78%) were acute positive responders tointravenous adenosine and about 4 patients (66%) were long term responders to CCB during 3monthsfollow up echocardiography.Conclusions: There is some discrepancy in the mean PAP between Doppler echo and RHC within ±10mm Hg for pulmonary artery pressure estimates. 15.7% of patients at RHC were acute positiveresponder to intravenous adenosine and half of them were long term responder to CCB.

Clinical study of patients with primary pulmonary hypertension (PPH)

Background: Pulmonary hypertension (PH) is a hemodynamic and pathophysiological conditiondefined as an increase in mean pulmonary arterial pressure (PAP) ≥25 mmHg at rest as assessed byright heart catheterization (RHC). Although there is some underestimation and overestimation of PAPbetween transthoracic Doppler echo (DE) and RHC, Doppler echo remains an indispensable screeningtool for the assessment of PH.Objective: clinical evaluation of patients with primary pulmonary hypertension (PPH) and assessvasoreactivity testing to identify patients who may benefit from long term therapy with calcium channelblockers (CCBs).Patients and methods: This prospective study was performed in the cardiac catheterization division inAl-Zahraa teaching hospital in Al-Kut. We studied the prevalence of certain variables among forty twopatients with PPH from "March 2014 to Nov 2016" including the clinical triggers, electrocardiographic(ECG) changes, Echocardiographic variables , RHC and vasoreactivity test with intravenous adenosineto identify acute positive responders and long term responders to CCB.Results: A total of forty two patients, female to male ratio were 2.8:1 with a mean age of 38±10(years).Dyspnea is a common clinical trigger (85%). Abnormal ECG was found in (90.5%) of patients, themajority had right ventricular hypertrophy (RVH) (76.2%). Echocardiographically all patients hadRVH. There was some differences in mean PAP (36±4.9mmhg) derived by DE from that obtained byRHC (47±4.78mmhg). RHC reveal that 6 patients (15.78%) were acute positive responders tointravenous adenosine and about 4 patients (66%) were long term responders to CCB during 3monthsfollow up echocardiography.Conclusions: There is some discrepancy in the mean PAP between Doppler echo and RHC within ±10mm Hg for pulmonary artery pressure estimates. 15.7% of patients at RHC were acute positiveresponder to intravenous adenosine and half of them were long term responder to CCB.

Advanced imaging in pulmonary hypertension: emerging techniques and applications.

Pulmonary hypertension (PH) is a pathophysiological disorder defined by an increase in pulmonary arterial pressure which can occur in multiple clinical conditions. Irrespective of etiology, PH entails a negative impact on exercise capacity and quality of life, and is associated with high mortality particularly in pulmonary arterial hypertension. Noninvasive imaging techniques play an important role in suggesting the presence of PH, providing noninvasive pulmonary pressure measurements, classifying the group of PH, identifying a possibly underlying disease, providing prognostic information and assessing response to treatment. While echocardiography, computed tomography (CT) and ventilation/perfusion scans are an integral part of routine work-up of patients with suspected PH according to current guidelines and across centers, innovative new techniques and applications in the field of PH such as 3D echocardiography, dual-energy CT, 4D flow magnetic resonance imaging (MRI), T1 and extracellular volume fraction mapping, non-contrast-enhanced MRI sequences for perfusion and ventilation assessment, and molecular-targeted positron emission tomography are emerging. This review discusses advanced and emerging imaging techniques in diagnosis, prognostic evaluation and follow-up of patients with PH.

Right ventricular dyssynchrony during hypoxic breathing but not during exercise in healthy subjects: a speckle tracking echocardiography study.

What is the central question of this study? Right ventricular dyssynchrony in severe pulmonary hypertension is associated with a poor prognosis. However, it has recently been observed in patients with lung or connective tissue disease and pulmonary artery pressure at the upper limits of normal. The mechanisms of right ventricular dyssynchrony in pulmonary hypertension remain uncertain. What is the main finding and its importance? Acute hypoxic breathing, but not normoxic exercise, induces an increase in right ventricular dyssynchrony detected by speckle tracking echocardiography in healthy subjects. These results add new insights into the determinants of right ventricular dyssynchrony, suggesting a role for systemic factors added to afterload in the pathophysiology of right ventricular inhomogeneity of contraction. Pulmonary hypertension (PH) has been shown to be associated with regional inhomogeneity (or dyssynchrony) of right ventricular (RV) contraction. Right ventricular dyssynchrony is an independent predictor of decreased survival in advanced PH, but has also been reported in patients with only mildly elevated pulmonary artery pressure (PAP). The mechanisms of RV dyssynchrony in PH remain uncertain. Our aim was to evaluate RV regional function in healthy subjects during acute hypoxia and during exercise. Seventeen healthy subjects (24±6years) underwent a speckle tracking echocardiography of the RV at rest in normoxia and every 15min during a 60min exposure to hypoxic breathing ( 12%). Ten of the subjects also underwent an incremental cycle ergometry in normoxia to 100W, with the same echocardiographic measurements. Dyssynchrony was measured as the SD of the times to peak systolic strain of the four basal and mid RV segments corrected for the heart rate (RV-SD4). RV-SD4 increased during hypoxia from 12±7 to 22±11ms in spite of mild increases in mean PAP (mPAP) from 15±2 to 20±2mmHg and pulmonary vascular resistance (PVR) from 1.18±0.15 to 1.4±0.15 Wood units (WU). During exercise RV-SD4 did not significantly change (from 12±6ms to 14±6ms), while mPAP increased to 25±2mmHg and PVR was unchanged. These data show that in healthy subjects, RV contraction is inhomogeneous in hypoxia but not during exercise. Since PAP increases more during exercise, RV dyssynchrony in hypoxia may be explained by a combination of mechanical (RV afterload) and systemic (hypoxia) factors.

Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboembolic disease.

Symptomatic patients with chronic thromboembolic disease (CTED) without pulmonary hypertension often show an excessive increase in mean pulmonary arterial pressure (MPAP) during exercise.We report on the impact of pulmonary endarterectomy (PEA) on pulmonary haemodynamics in a prospective series of 32 consecutive CTED patients who underwent PEA. All patients had a comprehensive diagnostic work-up including right heart catheterisation at baseline and 12 months after PEA. Furthermore, in 12 patients exercise right heart catheterisation was performed before and after PEA.After PEA, MPAP was lower at rest (20±3 versus 17±3 mmHg; p=0.008) and during maximal exercise (39±8 versus 31±6 mmHg; p=0.016). The mean total pulmonary resistance (TPR) decreased from 3.6±0.8 Wood Units (WU) pre-operatively to 2.7±0.7 WU 1 year after PEA (p=0.004) and the mean slope of the MPAP/cardiac output (CO) relationship decreased from 3.6±1.0 to 2.3±0.8 WU (p=0.002). Peak oxygen uptake increased from 1.2±0.4 to 1.5±0.3 L·min-1 (p=0.014) and ventilatory equivalents of carbon dioxide decreased from 39±2 to 30±2 (p=0.002). There was a significant improvement in quality of life assessed by the Cambridge Pulmonary Hypertension Outcome Review questionnaire.In CTED patients, PEA resulted in haemodynamic and clinical improvements. The means of TPR and MPAP/CO slopes decreased to <3.0 WU.

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.

Macitentan reduces progression of TGF-β1-induced pulmonary fibrosis andpulmonary hypertension.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with an unknown cause. Two drugs, nintedanib and pirfenidone, have been shown to slow, but not stop, disease progression. Pulmonary hypertension (PH) is a frequent complication in IPF patients and is associated with poor prognosis. Macitentan is a dual endothelin receptor antagonist that is approved for pulmonary arterial hypertension treatment. We hypothesised that using macitentan to treat animals with pulmonary fibrosis induced by adenoviral vector encoding biologically active transforming growth factor-β1 (AdTGF-β1) would improve the PH caused by chronic lung disease and would limit the progression of fibrosis.Rats (Sprague Dawley) which received AdTGF-β1 were treated by daily gavage of macitentan (100 mg·kg-1·day-1), pirfenidone (0.5% food admix) or a combination from day 14 to day 28. Pulmonary artery pressure (PAP) was measured before the rats were killed, and fibrosis was subsequently evaluated by morphometric measurements and hydroxyproline analysis.AdTGF-β1 induced pulmonary fibrosis associated with significant PH. Macitentan reduced the increase in PAP and both macitentan and pirfenidone stopped fibrosis progression from day14 to day 28. Macitentan protected endothelial cells from myofibroblast differentiation and apoptosis whereas pirfenidone only protected against fibroblast-to-myofibroblast differentiation. Both drugs induced apoptosis of differentiated myofibroblasts in vitro and in vivoOur results demonstrate that dual endothelin receptor antagonism was effective in both PH and lung fibrosis whereas pirfenidone only affected fibrosis.

Postoperative Bedside Critical Care of Thoracic Surgery Patients.

Postoperative Bedside Critical Care of Thoracic Surgery Patients.

Characteristics of circular RNA expression in lung tissues from mice with hypoxia‑induced pulmonary hypertension.

Pulmonary hypertension (PH) is a life-threatening lung disease, characterized by an increase in pulmonary arterial pressure caused by vasoconstriction and vascular remodeling. The pathogenesis of PH is not fully understood, and there is a lack of potential biomarkers for the diagnosis and treatment of patients with PH. Non-coding RNAs with a characteristic covalently closed loop structure, termed circular RNAs (circRNAs), are present in a number of pulmonary diseases. To the best of our knowledge, the present study is the first to use microarray analysis to determine the expression profile of circRNAs in lung tissues from mice with hypoxia-induced PH. In total, 23 significantly upregulated and 41 significantly down-regulated circRNAs were identified. Of these, 12 differentially expressed circRNAs were selected for further validation using reverse transcription-quantitative polymerase chain reaction. Putative microRNAs (miRNAs) that bind to the dysregulated circRNAs were predicted. Subsequently, bioinformatics tools were used to construct circRNA-miRNA-mRNA networks for the two most promising circRNAs, namely mmu_circRNA_004592 and mmu_circRNA_018351. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of target genes of the dysregulated circRNAs revealed that these dysregulated circRNAs may serve an important role in the pathogenesis of hypoxia-induced PH. Therefore, these dysregulated circRNAs are candidate diagnostic biomarkers and potential therapeutic targets for PH.

Principles of pharmacological correction of pulmonary arterial hypertension

Definition and classification: Pulmonary hypertension (PH) is a group of life-threatening progressive diseases of various genesis, characterized by a progressive increase in arterial pressure (AP) in the pulmonary artery (PA), the remodeling of pulmonary vessels, which leads to an increase in pulmonary vascular resistance and pulmonary arterial pressure and more often leads to right ventricular heart failure and premature death. Pulmonary hypertension is clinically divided into five groups: patients in the first group have idiopathic pulmonary arterial hypertension (IPAH), whereas in patients of other groups secondary PH associated with cardiopulmonary or other systemic diseases is observed. The development of secondary LH is caused by congenital heart defects, collagenoses, presence of thrombus in the pulmonary artery, prolonged high pressure in the left atrium, hypoxemia, chronic obstructive pulmonary diseases (COPDs). In case of secondary PH, thrombosis and other changes in the pulmonary veins occur.&#x0D; Ways of pharmacological correction of pulmonary hypertension: Over the last decade pharmacotherapy of PH has been developing rapidly, and the introduction of modern methods of treatment, especially for primary PAH, has led to positive results. However, despite the progress in treatment, the functional limitations and survival of patients remain unsatisfactory. Currently, there are two levels of treatment for pulmonary hypertension: primary and specific pathogenetic therapies. Primary therapy is aimed at the main cause of PH. It also includes supportive therapy. Pathogenetic therapy includes prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Tactics of therapy can be established on the basis of either clinical classification, or functional class. Prostanoids are a promising group of drugs for the treatment of pulmonary arterial hypertension (PAH), since they possess not only vasodilating, but also antiplatelet and antiproliferative actions. Therefore, it seems logical to use prostacyclin and its analogs to treat patients with various forms of PAH.

Successful treatment of suckling Red Angus calves for bovine respiratory disease is not associated with increased mean pulmonary arterial pressures at weaning.

The purposes of this study were to determine if the successful treatment of bovine respiratory disease (BRD) in suckling calves was associated with a long-term increase in mean pulmonary arterial pressure (mPAP) and, to screen for associations between blood leukogram variables and mPAP. A cohort of Red Angus calves (n = 74) were followed from birth to weaning at an altitude of 975 m. Calves were weaned at 172 ± 14 d when their mPAP was measured and whole blood collected. Thirty calves that had been treated for BRD (34 to 45 d prior) and 30 calves that had not required treatment for BRD were sampled. Treatment for BRD had no effect on mPAP (P = 0.37). Mean mPAP was 48 ± 8 mm Hg (± SD) with a minimum of 34 mm Hg and a maximum at 69 mm Hg. Weaning weight and sex tended to be associated with mPAP, but they explained just 5% of the variation in mPAP (P = 0.08; Adj. r2 = 0.05). Fibrinogen (P = 0.008) and absolute lymphocyte count (P = 0.06) were negatively associated with mPAP, whereas absolute monocyte count was positively associated with mPAP (P = 0.01). The findings of this study suggest that pre-weaning treatment for BRD does not increase a calves’ post-weaning risk of congestive right heart failure. Further, components of the immune and acute phase response system may play a role in the development and progression of pulmonary hypertension.

Effects of human relaxin-2 (serelaxin) on hypoxic pulmonary vasoconstriction during acute hypoxia in a sheep model.

PurposeHypoxia induces pulmonary vasoconstriction with a subsequent increase of pulmonary artery pressure (PAP), which can result in pulmonary hypertension. Serelaxin has shown an increase of pulmonary hemodynamic parameters after serelaxin injection. We therefore investigated the response of pulmonary hemodynamic parameters after serelaxin administration in a clinically relevant model.MethodsSix controls and six sheep that received 30 μg/kg serelaxin underwent right heart catheterization during a 12-minute hypoxia period (inhalation of 5% oxygen and 95% nitrogen) and subsequent reoxygenation. Systolic, diastolic, and mean values of both PAP (respectively, PAPs, PAPd, and PAPm) and pulmonary capillary wedge pressure (respectively, PCWPs, PCWPd, and PCWPm), blood gases, heart rate (HR), and both peripheral and pulmonary arterial oxygen saturation were obtained. Cardiac output (CO), stroke volume (SV), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAcompl), and systemic vascular resistance (SVR) were calculated.ResultsThe key findings of the current study are that serelaxin prevents the rise of PAPs (p≤0.001), PAPm, PCWPm, PCWPs (p≤0.03), and PAPd (p≤0.05) during hypoxia, while it simultaneously increases CO and SV (p≤0.001). Similar courses of decreases of PAPm, PAPd, PAPs, CO, SVR (p≤0.001), and PCWPd (p≤0.03) as compared to hypoxic values were observed during reoxygenation. In direct comparison, the experimental groups differed during hypoxia in regard to HR, PAPm, PVR, and SVR (p≤0.03), and during reoxygenation in regard to HR (p≤0.001), PAPm, PAPs, PAPd, PVR, SVR (p≤0.03), and PCWPd (p≤0.05).ConclusionThe findings of this study suggest that serelaxin treatment improves pulmonary hemodynamic parameters during acute hypoxia.

Pulmonary cement embolism following cement-augmented fenestrated pedicle screw fixation in adult spinal deformity patients with severe osteoporosis (analysis of 2978 fenestrated screws).

There is very limited information about pulmonary cement embolism (PCE) following cement-augmented fenestrated pedicle screw (CAFPS)fixation in the literature. The aim of this study to report the incidence of PCE following CAFPS fixation in adult deformity patients with severe osteoporosis and to identify risk factors such as; the number of levels, number of screws, and the cement volume used. 281 patients (204F, 77M) in whom CAFPS fixation was used during deformity surgery were included. All patients' routine postop 2 day chest X-rays and any available CT scans were reviewed by two radiologists. In patients with PCE, preop, early postop, and latest echocardiography studies were compared in terms of changes in pulmonary artery pressure (PAP) and right ventricular dilatation. Estimated cement volume used was calculated as: 2cc (1cc + 1cc) per thoracic and 3cc (1.5cc + 1.5cc) per lumbar levels, which are our routine protocol. Statistical analysis for risk factors was assessed with point biserial correlation test. Average age is 70.5 (51-89) and average follow-up is 3.2years (2-5). A total of 2978 CAFPS were instrumented with a mean of 10.5 levels (2-16) in 281 patients. PCE was diagnosed radiologically in 46 patients (16.3%). Among these 46 patients, PCE was clinically symptomatic in only 4 patients. Overall incidence of symptomatic PCE was 1.4% (4 of 281). Symptomatic PCE was statistically significant: when CAFPS fixation was performed > 7 levels; > 14 screws were used, and > 20-25cc cement was used for augmentation (r = 0.378). In PCE group, mean preop PAP values of 27.40 (20-37)mm/Hg increased to 32.34 (20-50) mm/Hg in early postop and decreased to 28.29 (18-49)mm/Hg at final follow-up. In symptomatic PCE patients, mean preop PAP values of 30.75 (28-36)mm/Hg increased to 45.74 (40-50)mm/Hg in early postop and decreased to 38.75 (37-40)mm/Hg at final follow-up. This study showed an overall 16.3% radiological PCE and 1.4% symptomatic PCE incidence when CAFPS were used due to severe osteoporosis. The symptomatic PCE risk was significant when CAFPS were > 7 levels; > 14 fenestrated screws; and > 20-25cc cement volume is used and this may cause PAP increase and right ventricular dilatation.

Depression and Anxiety in Patients With Pulmonary Hypertension: The Role of Life Satisfaction and Optimism

Pulmonary hypertension is a highly disabling condition characterized by a progressive increase in pulmonary arterial pressure. Even though pulmonary hypertension may cause great emotional distress, research examining the determinants of patients' emotional well-being has been scarce and has mostly focused on the role of disease-related factors. This study examined whether patients' emotional well-being may be effected by their life circumstances. Sixty-four patients with pulmonary hypertension completed measures of symptoms of pulmonary hypertension, functional disability, depression and anxiety symptoms, life satisfaction, optimism, and quality of life (QoL). Clinically-significant symptoms of depression and anxiety were only accurately predicted in 50.5% and 56.5% of patients, respectively, based on disease severity alone. However, the addition of life satisfaction and optimism to the models improved the prediction of depressive and anxiety symptomatology. Further, symptoms of anxiety were a significant predictor of QoL, above and beyond disease severity. Patients with considerably different levels of disease severity may develop clinically-significant depressive and anxiety symptomatology. This suggests that there is not a perfect correspondence between the level of disease severity and the repercussions thereof across patients. Accordingly, these results suggest that emotional well-being may be better explained by taking into consideration patients' life circumstances, as these may modulate the repercussions of having pulmonary hypertension. The results also showed that anxiety symptoms constituted an extra burden to patients' QoL. The higher prevalence in this sample of clinically-significant symptoms of anxiety, compared to that of depression, suggest that feelings of fear and uncertainty may require special attention among patients with pulmonary hypertension.