Increase In Pulmonary Arterial Pressure Research Articles

High adventure shunts old notions of pulmonary vascular control during hypoxic exercise: contrasting views that might just burst your bubble!

High adventure shunts old notions of pulmonary vascular control during hypoxic exercise: contrasting views that might just burst your bubble!

Adverse outcomes associated with pulmonary hypertension in chronic obstructive pulmonary disease after bilateral lung transplantation

BackgroundThe impact of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) on survival after lung transplantation (LTx) is not known. Material and methodsFirst-time adult LTx recipients with COPD transplanted between May 2005 and September 2013 were identified in the United Network for Organ Sharing Registry database, and tracked from transplant date until death or censoring. Right heart catheterization (RHC) measurements at time of wait listing were used to predict all-cause mortality after LTx, with multivariable analyses stratified by transplant type. ResultsOf 3362 COPD LTx recipients, 3105 were included in the analytic sample, with multiple imputation used to complete missing data on covariates. Multivariable analysis found the hazard of death to increase with a 10 mmHg increase in mean pulmonary artery pressure (mPAP) among recipients of bilateral LTx (HR = 1.12; 95% CI = 1.01, 1.24; p = 0.032), but not among recipients of single LTx (HR = 0.92; 95% CI = 0.80, 1.06; p = 0.234). ConclusionPH prior to bilateral LTx in patients with COPD is associated with higher mortality risk.

Diagnosis and Treatment of Pulmonary Hypertension

pulmonary hypertension (PH) is a hemodynamic and clinical state defined as an increase in mean pulmonary arterial pressure ≥25mmHg at rest. Five groups of patients have been defined: group 1 as pulmonary arterial hypertension (PAH), group 2 as PH due to left heart disease, group 3 as PH due to lung diseases, group 4 as chronic thromboembolic PH, and group 5 as PH of other causes. PAH is a rapidly progressive and fatal disease with an incidence of 3 cases per million whereas incidence of PH due to left ventricular dysfunction is as high as 60-70% of all cases. Pulmonary capillary wedge pressure, invasively measured at rest, has been used to distinguish between pre- (≤15mmHg) and post-capillary (>15mmHg) PH. The early clinical symptoms and signs are subtle and non-specific, such as exertional dyspnea, fatigue, pre-syncope and progressive limitation of exercise capacity so the vast majority of patients have an advanced disease with World Health Organization functional class of III or IV at first presentation. The diagnostic approach in PH has the goal to evaluate the two main anatomic components: pulmonary vasculature and right ventricle in order to establish the diagnosis and identify the group of PH. The therapy for PAH patients includes three main components: general measures and supportive therapy; initial therapy with calcium channel blockers in vasoreactive or specific drugs approved for PAH in non-vasoreactive patients either single or in combination, and lung transplantation. All patients with PAH should be referred to PH expert centers for comprehensive diagnostic and therapeutic assessment.

Exercise Facilitates Early Detection of Cardiac and Vascular Remodelling During Development of Chronic Thrombo‐Embolic Pulmonary Hypertension in a Novel Swine Model

BackgroundPulmonary hypertension (PH) is a chronic disease of the pulmonary vasculature characterized by impaired pulmonary hemodynamics and vascular remodeling which often progresses to right heart failure with high mortality. One subform of PH is chronic thrombo‐embolic pulmonary hypertension (CTEPH) which develops in 4% of patients after a pulmonary embolism and is characterized by remodeling of the distal, unobstructed pulmonary vasculature.PurposeHere we studied the progression of pulmonary vascular disease as well as the adaptation of the right ventricle to the increased after load, by repeated measurement of hemodynamics at rest and during graded treadmill exercise in a novel swine model of CTEPH.MethodsSwine (n=16) of either sex (23±1kg) were chronically instrumented with catheters (right ventricle (RV), pulmonary artery, left atrium and aorta) for hemodynamic measurements and blood sampling. Additionally, a flow probe was placed around the ascending aorta to measure cardiac output. CTEPH was induced in 8 swine by up to 4 weekly infusions of microspheres (Ø700μm, total ~40,000.‐spheres) into the pulmonary circulation, followed by 4–6 weeks of follow‐up without embolisations. In addition, the CTEPH animals received daily L‐NG‐Nitroarginine methyl ester (L‐NAME) i.v. (30mg·kg−1·day−1, week 1–7), During total follow‐up (7–10 weeks), hemodynamics at rest and during exercise were obtained. RV dimensions were weekly assessed using echocardiography.ResultsRepeated embolisation of the pulmonary vasculature resulted in a progressive increase in mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance index (tPVRi, Table). tPVRi did not change during exercise in either the control or CTEPH swine. At the end of the embolisation period at 4 weeks, the increase in MPAP during exercise was maintained in CTEPH swine while the increase in cardiac index (CI) was attenuated. Despite a lower arterial oxygen content (CaO2) in CTEPH swine, body oxygen consumption (BVO2) was maintained at rest and during exercise by an increase in oxygen extraction resulting in a decreased mixed venous oxygen content (CVO2). After 8 weeks of follow‐up, the increase of MPAP and tPVRi and decrease of CI were sustained at rest, while oxygen extraction in CTEPH swine had returned towards control levels. However, although CI did increase during exercise, the exercise‐induced increase in BVO2 was attenuated due to arterial desaturation.The sustained increase in after load resulted in RV dilation (RV end‐diastolic area index increased from 27±2mm2·kg−1 to 35±3mm2·kg−1 in control vs CTEPH, week 8, P=0.03) and RV hypertrophy (Fulton index increased from 0.44±0.01 to 0.52±0.03, P=0.02).ConclusionsRepeated embolization results in CTEPH in swine, with a progressive increase in tPVRi. The early phase of CTEPH is characterized by RV dilation and dysfunction, as evidenced by the inability of the RV to increase CI commensurate with the increase in body oxygen consumption. When PH is sustained, RV hypertrophy occurs, which, together with an increase in heart rate is able to increase CI during exercise.Support or Funding InformationCVON2012‐08‐PHAEDRA Effect of exercise and time on hemodynamic and oxygenation status in CTEPH development. Variable Follow‐up (wk) CON rest CON ex CTEPH rest CTEPH ex MPAP (mmHg) 0 19 ± 1 33 ± 2* 22 ± 1# 33 ± 3* 4 19 ± 1 34 ± 2* 32 ± 4^# 56 ± 8*# 8 21 ± 1 38 ± 5* 41 ± 8^# 68 ± 10*# tPVRi (mmHg·L−1·kg−1) 0 106 ± 7 121 ± 11 92 ± 6 97 ± 11 4 118 ± 8 124 ± 9 151 ± 29^ 216 ± 39# 8 120 ± 10 159 ± 20 374 ± 147^# 323 ± 51# Cl (L·kg−1) 0 0.18 ± 0.01 0.28 ± 0.03* 0.25 ± 0.03# 0.35 ± 0.03* 4 0.17 ± 0.01 0.28 ± 0.02* 0.21 ± 0.06^ 0.27 ± 0.03 8 0.16 ± 0.01 0.25 ± 0.02* 0.14 ± 0.02^$ 0.22 ± 0.02* BVO2i (mmol·min−1·kg−1) 0 0.45 ± 0.02 1.09 ± 0.08* 0.58 ± 0.08^ 1.36 ± 0.16*# 4 0.43 ± 0.03 1.18 ± 0.10* 0.64 ± 0.16 1.05 ± 0.12* 8 0.45 ± 0.03 1.25 ± 0.09* 0.31 ± 0.06$ 0.85 ± 0.08*# CaO2 (mL O2·dL−1) 0 5.75 ± 0.22 5.53 ± 0.23 5.53 ± 0.22 5.69 ± 0.12 4 5.89 ± 0.21 6.52 ± 0.31* 5.45 ± 0.18$ 5.99 ± 0.29*# 8 6.03 ± 0.25 6.90 ± 0.25* 5.86 ± 0.26 6.14 ± 0.21$ CvO2 (mL O2·dL−1) 0 3.34 ± 0.20 1.87 ± 0.16* 3.40 ± 0.10 2.03 ± 0.17* 4 3.32 ± 0.16 2.41 ± 0.23* 2.90 ± 0.29$ 1.99 ± 0.38*$ 8 3.32 ± 0.18 2.06 ± 0.30* 3.16 ± 0.21 1.58 ± 0.39* p<0.05 effect of exercise; p<0.05 compared to week 0 all at rest; p<0.05, p<0.1 CTEPH vs Control same week and exercise level; con, control animals; ex, exercise.

Retrospective evaluation of pimobendan and sildenafil therapy for severe pulmonary hypertension due to lung disease and hypoxia in 28 dogs (2007-2013).

Pulmonary hypertension (PH) is the persistent abnormal increase in pulmonary artery (PA) pressure and in dogs is usually secondary to congenital disease causing pulmonary over circulation, chronic respiratory disease and elevated left atrial pressure. Sildenafil (SF) is a phosphodiesterase (PDE) V inhibitor that causes pulmonary artery (PA) vasodilation by increasing pulmonary vascular concentrations of cyclic guanosine monophosphate which subsequently increases the activity of endogenous nitric oxide. Pimobendan (PB) is a PDE III inhibitor with calcium sensitizing effects thereby exerting positive inotropy and vasodilation. The purpose of this retrospective study was to evaluate the long‐term survival of dogs with severe PH treated with SF and PB compared to SF alone. The use of PB in combination with SF did not result in a statistically significant increase in survival times in dogs with pulmonary hypertension secondary to chronic respiratory disease compared to SF alone.

Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise.

Exercise is a stress to the pulmonary vasculature. With incremental exercise, the pulmonary diffusing capacity (DLCO) must increase to meet the increased oxygen demand; otherwise, a diffusion limitation may occur. The increase in DLCO with exercise is due to increased capillary blood volume (Vc) and membrane diffusing capacity (Dm). Vc and Dm increase secondary to the recruitment and distension of pulmonary capillaries, increasing the surface area for gas exchange and decreasing pulmonary vascular resistance, thereby attenuating the increase in pulmonary arterial pressure. At the same time, the recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) during exercise may contribute to gas exchange impairment and/or prevent large increases in pulmonary artery pressure.We describe two techniques to evaluate pulmonary diffusion and circulation at rest and during exercise. The first technique uses multiple-fraction of inspired oxygen (FIO2) DLCO breath holds to determine Vc and Dm at rest and during exercise. Additionally, echocardiography with intravenous agitated saline contrast is used to assess IPAVAs recruitment.Representative data showed that the DLCO, Vc, and Dm increased with exercise intensity. Echocardiographic data showed no IPAVA recruitment at rest, while contrast bubbles were seen in the left ventricle with exercise, suggesting exercise-induced IPAVA recruitment.The evaluation of pulmonary capillary blood volume, membrane diffusing capacity, and IPAVA recruitment using echocardiographic methods is useful to characterize the ability of the lung vasculature to adapt to the stress of exercise in health as well as in diseased groups, such as those with pulmonary arterial hypertension and chronic obstructive pulmonary disease.

Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise

Exercise is a stress to the pulmonary vasculature. With incremental exercise, the pulmonary diffusing capacity (DLCO) must increase to meet the increased oxygen demand; otherwise, a diffusion limitation may occur. The increase in DLCO with exercise is due to increased capillary blood volume (Vc) and membrane diffusing capacity (Dm). Vc and Dm increase secondary to the recruitment and distension of pulmonary capillaries, increasing the surface area for gas exchange and decreasing pulmonary vascular resistance, thereby attenuating the increase in pulmonary arterial pressure. At the same time, the recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) during exercise may contribute to gas exchange impairment and/or prevent large increases in pulmonary artery pressure. We describe two techniques to evaluate pulmonary diffusion and circulation at rest and during exercise. The first technique uses multiple-fraction of inspired oxygen (FIO2) DLCO breath holds to determine Vc and Dm at rest and during exercise. Additionally, echocardiography with intravenous agitated saline contrast is used to assess IPAVAs recruitment. Representative data showed that the DLCO, Vc, and Dm increased with exercise intensity. Echocardiographic data showed no IPAVA recruitment at rest, while contrast bubbles were seen in the left ventricle with exercise, suggesting exercise-induced IPAVA recruitment. The evaluation of pulmonary capillary blood volume, membrane diffusing capacity, and IPAVA recruitment using echocardiographic methods is useful to characterize the ability of the lung vasculature to adapt to the stress of exercise in health as well as in diseased groups, such as those with pulmonary arterial hypertension and chronic obstructive pulmonary disease.

Pulmonary Hypertension: Scientometric Analysis and Density-Equalizing Mapping.

Pulmonary hypertension (PH) is characterized by the increase of the mean pulmonary arterial pressure in the lung circulation. Despite the large number of experimental and clinical studies conducted on pulmonary hypertension, there is no comprehensive work that analyzed the global research activity on PH so far. We retrieved the bibliometric data of the publications on pulmonary hypertension for two periods from the Web of science database. Here, we set the first investigation period from 1900 to 2007 (t1) due to the cited half life of articles and the relating difficulties to interpret the citation parameters. The second evaluation period (t2) covers the time interval from 2008 onwards including the year 2015. The data were analyzed and processed to density-equalizing maps using the NewQIS platform. A total number of 18,986 publications were identified in t1 that come from 85 countries. The US published the highest number of publications (n = 7,290), followed by the UK, Germany, Japan and France. In t2 19,676 items could be found worked out by 130 countries. The raking started just the same with the USA as most publishing nation with 7,127 publications on PH, followed by the UK and Germany. Japan fell back on 6th place, whereas China came into view on the 5th position. Analyzing the average citation rate as a parameter for research quality, Mexico reached the highest value in t1 and Ireland in t2. While, the country specific h-index underlined the leading position of the US research in both evaluation periods again. The average number of international collaboration items was expanding from none in 1978 to 530 items in 2015 with the USA as the country with the highest number of collaboration articles. The present study is the first large scale density-equalizing mapping and scientometric analysis of global PH research activity. Our data draw a sketch of the global research architecture in this field, indicating a need for specific research programs in countries with a lower human development index.

Therapeutic effect of prostaglandin E1 in monocrotaline-induced pulmonary arterial hypertension rats

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration. However, many of the currently available anti-PAH drugs suffer from a number of limitations, including short biological half-life, and poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with selectivity toward pulmonary circulation when it is administered via the pulmonary route. However, PGE1 has a very short half-life of 5–10 minutes. Therefore, we hypothesized that long-term effect of PGE1 could reduce mal-adaptive structural remodeling of the lung and heart and prevent ventricular arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and endothelin receptor A, and the expression of fibrosis. These results support the notion that PGE1 can improve the functional properties of RV, highlighting its potential benefits for heart and lung impairment.

Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats.

PurposePulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressure leading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs) administered via the jugular vein have been previously shown to improve PAH by reversal treatment. However, the effect of low dosage and transfusion timing of hUCB-MSCs on PAH has not yet been clearly established. Obviously, low dosage treatment can lead to a reduction in costs. This is the first study on early transfusion effect.Materials and MethodsThis study was divided into two parts. The first part is an investigation of dose-dependent effect. hUCB-MSCs were administered into 3 groups of rats (UA: 3×106 cells, UB: 1.5×106 cells, UC: 3×105 cells) via the external jugular vein at week 1 after monocrotaline (MCT) injection. The second part is a search for optimal treatment timing in 3×105 cells dose of hUCB-MSCs administered at day 1 for UD group (low dose of hUCB-MSCs at day 1), at day 1 and week 1 for the UE group (dual transfusion of low dose of hUCB-MSCs at day 1 and week 1) and at 1 week for the UF group (reversal treatment of low dose hUCB-MSC at week 1) after MCT injection.ResultsThe administration of 3×105 hUCB-MSCs was as effective as the 3×106 dose in decreasing mean right ventricle (RV) pressure and pulmonary pathological changes. Early treatment with hUCB-MSCs improved mean RV pressure, pulmonary pathological changes and heart collagen 3 protein expression levels in PAH.ConclusionLow-dose early treatment of hUCB-MSCs is as effective as a high dose treatment of hUCB-MSCs in improving PAH although dual or reversal treatment is still more effective.

Challenges in the development of chronic pulmonary hypertension models in large animals.

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals.

Study the Pulmonary Hypertension among Heavy Smokers Young Adult Males before the Clinical Evidences of Chronic Lung Disease

Background: Smoking is a well-known risk factor for development of COPD. Prevalence of smoking is high. Its effect on the pulmonary pressure before the development of COPD still needs to be explored on human model. Aim of the study: The aim of the study is to evaluate the pulmonary hypertension in young heavy smokers adult population prior to the development of the clinical and the abnormal pulmonary function test. Material and Methods: The study was carried out at Al Sader Najaf Teaching Hospital during the period April 2015 to April 2016 where 93 Smokers who smoke at least 2 packets/day for minimal two years period were included in the study with 93 non-smokers used as a control group. The age of the smokers group and non- smokers group was less than 40 year with mean age 25 ± 4.1 for smokers and 24.9 ± 3 for non –smokers. BMI for all was >30. All had their pulmonary function test with the clinical examination to exclude any evidences of the chronic lung disease. Transthoracic Echocardiography and Doppler study was done for the smokers and non-smokers groups to evaluate the Maximum tricuspid valve velocity, the Mean pulmonary pressure gradient and the Pulmonary artery pressure. Results: Mean tricuspid maximum velocity (TGmax) for smokers was 0.9 ± 0.1 and for non-smokers 0.60 ± 0.20 (p value less than 0.001). The mean pulmonary pressure gradient for smokers was 3.4 ± 1.0 and for non-smokers 1.5 ± 0.8 with p value less than 0.001. The mean pulmonary artery pressure for smokers group was 12.2 ± 1.6 and for non-smokers group 7.0 ± 1.2 with p value less than 0.001. Conclusion: There is an increase in the pulmonary arterial pressure among the heavy smokers young adults when was compared with the non-smokers young adults.

Molecular Basis of Nitrative Stress in the Pathogenesis of Pulmonary Hypertension.

Pulmonary hypertension (PH) is a lung vascular disease with marked increases in pulmonary vascular resistance and pulmonary artery pressure (>25mmHg at rest). In PH patients, increases in pulmonary vascular resistance lead to impaired cardiac output and reduced exercise tolerance. If untreated, PH progresses to right heart failure and premature lethality. The mechanisms that control the pathogenesis of PH are incompletely understood, but evidence from human and animal studies implicate nitrative stress in the development of PH. Increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) result in nitrative stress, which in turn induces posttranslational modification of key proteins important for maintaining pulmonary vascular homeostasis. This affects their functions and thereby contributes to the pathogenesis of PH. In this chapter, molecular mechanisms underlying nitrative stress-induced PH are reviewed, molecular sources of ROS and RNS are delineated, and evidence of nitrative stress in PH patients is described. A better understanding of such mechanisms could lead to the development of novel treatments for PH.

COMPARISON OF THE DISORDERED MECHANICAL FUNCTION OF THE LEFT ATRIUM AFTER ANTRAL ISOLATION OF PULMONARY VEINS BY RADIOFREQUENCY OR CRYOBALLOON ABLATION

Aim. To assess and compare mechanical functioning of the left atrium before and just after cryoballoon or radiofrequency ablation. Material and methods . Totally, 43 patients included, with sympthomatic atrial fibrillation resistant to drug treatment. Of those 21 — for cryoballoon ablation (mean age 57,8±8,7 y. o., 11 males and 10 females) and 22 candidates for radiofrequency ablation, at the age 54,4±11 y. o., 16 males and 6 females. Before procedure, just after and on the 5th day, transthoracal echocardiography was performed, with measurement of Doppler parameters of intracardiac hemodynamics, as mechanical function of the left atrium assessment, including 3D imaging. Results. By the data from transthoracal echocardiography and direct intraoperation manometry, the significant disorders of the left atrium (LA) mechanical function were found in both treatment groups, with some differences. Pulmonary veins (PV) isolation by any method does not influence diastolic and systolic function of the left ventricle, that confirmed by invasive measurements of the end-diastolic pressure in LV, as the changes of volumes and ejection fraction by echocardiography. Therefore transmitral blood flow dynamics, as PV and pulmonary artery flow, related to PV isolation procedure, is a result of the LA functioning disorder due to its passive dilatability and active contractility decrease, dysfunction of the PV sleeves, increase of pulmonary vascular resistance. The significant decrease found in LA pumping function, more prominent in radiofrequency group just after the procedure, with further improvement to the 5th day after procedure. Also, mean pulmonary artery pressure increase, and till the 5th day in radiofrequency group it was significantly higher than in cryoablation group. Conclusion. Both cryo and radio ablation procedures of PV isolation significantly impact on the mechanical functioning of the LA, however cryo ablation leads to less severe disorder at short follow-up.

The Use of Macitentan in the Treatment of Out-of-Proportion Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease: Case Report

Pulmonary hypertension (PH) is an important complication of chronic pulmonary disease, especially of chronic obstructive lung disease (COPD). The exact prevalence of PH in COPD is unknown. PH is defined as an increase in mean pulmonary arterial pressure (PAPm) > 25 mmHg at rest as assessed by right heart catheterization . In most cases, PH in COPD patients is usually mild to moderate.

Right Ventricular Response During Exercise in Patients with Chronic Obstructive Pulmonary Disease.

Right ventricular (RV) pump function is of essential clinical and prognostic importance in a variety of heart and lung diseases. While the evaluation of RV performance at rest has been implemented in the clinical setting, it is unknown whether this assessment during exercise may provide additional benefit. With this aim, we evaluated the exercise-induced pulmonary arterial systolic pressure (PASP) increase during exercise in patients with severe chronic obstructive pulmonary disease (COPD) as an expression of RV contractile reserve. Cardiopulmonary exercise testing (CPET) with synchronic echocardiography was performed in 81 patients. Patients were classified into two groups according to an exercise-induced PASP increase above 30mmHg (High PSAP) or below 30mmHg (Low PSAP) during maximal exercise. Patients were then followed for three years. Sixteen patients (20%) had low PSAP and 65 (80%) showed high PSAP. These were not significant clinical and functional differences. Low PSAP was associated with a significantly lower peak VO2 (mean (SD), 35 (2) % predicted) compared to high PSAP response (peak VO2 45 (3) % predicted), p=0.045. Factors associated with mortality were age and exercise-induced PASP. Seventeen patients died during the three years of follow-up (7 (39%) in the low PSAP group and only 10 (1%) in the high PSAP group, p=0.041). Cardiopulmonary exercise testing with a synchronic echocardiography may be a useful tool for the assessment of RV contractile reserve in severe COPD patients. Exercise-induced PSAP emerges as a possible prognostic factor in these patients.

Search for an animal model to investigate selective pulmonary vasodilation.

Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation. To do so, a haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration deemed to be a sufficient time interval before and after a possible intervention. In anaesthetized and mechanically-ventilated Sprague-Dawley rats pulmonary hypertension was induced either by acute hypoxia due to reduction of the inspired oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were instrumented to measure right ventricular and systemic arterial pressures. Acute hypoxia caused a short, and only transient, increase of pulmonary artery pressure as well as profound systemic hypotension which suggested haemodynamic instability. U46619 infusion induced variable changes in the pulmonary and systemic vascular tone without sufficient stabilization within 30 min. MCT provoked sustained pulmonary hypertension with normal systemic pressure values and inhalation of nitric oxide caused selective pulmonary vasodilation. In conclusion, out of the three examined rat animal models only MCT-induced pulmonary hypertension is a solid and reliable model for investigating selective pulmonary vasodilation.

Left ventricular deformation at rest predicts exercise-induced elevation in pulmonary artery wedge pressure in patients with unexplained dyspnoea.

Impaired left ventricular (LV) deformation despite preserved LV ejection fraction (LVEF) is common and predicts outcomes in heart failure with preserved LVEF. We hypothesized that impaired LV deformation at rest is a marker of impaired cardiac systolic and diastolic reserve, and aimed to determine whether resting longitudinal (LS) and circumferential strain (CS) are associated with invasively measured haemodynamic response to exercise in patients with dyspnoea and a normal LVEF. We studied 85 patients with LVEF ≥50% and free of significant valvular disease who were referred for evaluation of dyspnoea. All patients underwent rest echocardiography followed by right heart catheterization and cardiopulmonary exercise testing with concomitant invasive haemodynamic monitoring. The LS, CS and CS/LS ratio were measured by two-dimensional speckle-tracking echocardiography at rest. Lower absolute LS at rest was associated with greater increase in pulmonary arterial wedge pressure (PAWP) from rest to peak exercise (r = 0.23, P = 0.034). In contrast, higher absolute CS at rest predicted a greater increase in PAWP (r = - 0.27, P = 0.032) and greater stroke volume augmentation with exercise (r = - 0.26, P = 0.021). Higher CS/LS ratio was most predictive of elevation in PAWP with exercise (r = 0.30, P = 0.015). Of the measures of LV systolic and diastolic function assessed, the CS/LS ratio resulted in the highest area under the curve and specificity for the presence of rest- or exercise-induced pulmonary venous hypertension. Left ventricular deformation at rest predicts exercise-induced rise in PAWP among patients with dyspnoea and a preserved LVEF. A pattern of rest deformation characterized by worse LS and exaggerated CS is most strongly associated with exercise-induced rise in PAWP.

Impact of Residual Mitral Regurgitation on Right Ventricular Systolic Function After Left Ventricular Assist Device Implantation

Significant mitral regurgitation (MR) is thought to decrease after left ventricular assist device (LVAD) implantation, and therefore repair of mitral valve is not indicated in current practice. However, residual moderate and severe MR leads to pulmonary artery pressure increase, thereby resulting in right ventricular (RV) dysfunction during follow-up. We examined the impact of residual MR on systolic function of the right ventricle by echocardiography after LVAD implantation. This study included 90 patients (mean age: 51.7 ± 10.9 years, 14.4% female) who underwent LVAD implantation (HeartMate II = 21, HeartWare = 69) in a single center between December 2010 and June 2014. Echocardiograms obtained at 3-6 months and over after implantation were analyzed retrospectively. RV systolic function was graded as normal, mild, moderate, and severely depressed. MR (≥moderate) was observed in 43 and 44% of patients at early and late period, respectively. Systolic function of the RV was severely depressed in 16 and 9% of all patients. Initial analysis (mean duration of support 174.3 ± 42.5 days) showed a statistically significant correlation between less MR and improved systolic function of RV (P = 0.01). Secondary echocardiographic analysis (following a mean duration of support of 435.1 ± 203 days) was also statistically significant for MR degree and RV systolic dysfunction (P = 0.008). Residual MR after LVAD implantation may cause deterioration of RV systolic function and cause right-sided heart failure symptoms. Repair of severe MR, in selected patients such as those with severe pulmonary hypertension and depressed RV, may be considered to improve the patient's clinical course during pump support.

Pulmonary vascular collagen content, not cross-linking, contributes to right ventricular pulsatile afterload and overload in early pulmonary hypertension.

The present study found an important role for collagen content, but not collagen cross-linking, in the pulsatile right ventricular (RV) afterload, which is correlated with RV hypertrophy. These results uncover a new collagen-mediated mechanical mechanism of RV dysfunction in early pulmonary hypertension progression. Furthermore, our results suggest that measures and metrics of pulsatile hemodynamics such as pulse pressure and pulse wave velocity are potentially important to cardiovascular mortality in patients with pulmonary hypertension.