Histologische Materialgewinnung bei pulmonaler Hypertonie mittels perkutaner, transvasaler Biopsie (PTB) – tierexperimentelle und erste klinische Daten (Histologic specimen from patients with pulmonary hypertension biopsy – results of animal experiments and clinical data)

A number of pressures have led to a very great reduction or complete abandonment of the use of animals in the teaching of physiology in most medical schools. Often animal experiments have been replaced by computer simulations, but a simulation is only as good as the model or algorithm on which it is based and can never contain the depth of information or unpredictability displayed by real animals or patients. We used a computer-based system to collect cardiovascular data from patients instrumented for cardiac surgery, allowing students to "replay" an operation. These recordings were annotated with notes, diagrams and video clips, and a student workbook was written. The resulting package contained a wealth of physiological data and was perceived by students to be very clinically relevant. The very wealth of information, however, tended to overwhelm students, and so a series of introductory Computer tutorials were written to provide students with the background necessary to cope with the clinical data.

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Signaling Pathways Involved in the Development of Bronchopulmonary Dysplasia and Pulmonary Hypertension

Children ◽

10.3390/children7080100 ◽

2020 ◽

Vol 7 (8) ◽

pp. 100

Author(s):

Rajamma Mathew

Keyword(s):

Pulmonary Hypertension ◽

Growth Factor ◽

Signaling Pathways ◽

Bronchopulmonary Dysplasia ◽

Premature Infants ◽

Animal Experiments ◽

Tissue Growth ◽

Inflammatory Stress ◽

Fibroblast Growth Factor 10 ◽

Endothelial Growth Factor

The alveolar and vascular developmental arrest in the premature infants poses a major problem in the management of these infants. Although, with the current management, the survival rate has improved in these infants, but bronchopulmonary dysplasia (BPD) is a serious complication associated with a high mortality rate. During the neonatal developmental period, these infants are vulnerable to stress. Hypoxia, hyperoxia, and ventilation injury lead to oxidative and inflammatory stress, which induce further damage in the lung alveoli and vasculature. Development of pulmonary hypertension (PH) in infants with BPD worsens the prognosis. Despite considerable progress in the management of premature infants, therapy to prevent BPD is not yet available. Animal experiments have shown deregulation of multiple signaling factors such as transforming growth factorβ (TGFβ), connective tissue growth factor (CTGF), fibroblast growth factor 10 (FGF10), vascular endothelial growth factor (VEGF), caveolin-1, wingless & Int-1 (WNT)/β-catenin, and elastin in the pathogenesis of BPD. This article reviews the signaling pathways entailed in the pathogenesis of BPD associated with PH and the possible management.

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A Simple Derived Prediction Score for the Identification of an Elevated Pulmonary Artery Wedge Pressure Using Precatheterization Clinical Data in Patients Referred to a Pulmonary Hypertension Center

CHEST Journal ◽

10.1378/chest.15-0819 ◽

2016 ◽

Vol 149 (5) ◽

pp. 1261-1268 ◽

Cited By ~ 4

Author(s):

Stefan E. Richter ◽

Kari E. Roberts ◽

Ioana R. Preston ◽

Nicholas S. Hill

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Clinical Data ◽

Prediction Score ◽

Pulmonary Artery Wedge Pressure ◽

Wedge Pressure

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AB0443 BIOMARKER SUCH AS IL-17, IL-21 AND TIMP-1, IS USEFUL FOR PREDICTING THE PATHOPHYSIOLOGY OF CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY HYPERTENSION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2765 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1249.2-1249

Author(s):

S. Nakashima ◽

T. Kameda ◽

H. Shimada ◽

M. Mahmoud Fahmy Mansour ◽

R. Wakiya ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Connective Tissue ◽

Immunosuppressive Therapy ◽

Connective Tissue Disease ◽

Clinical Data ◽

The Other ◽

Vascular Involvement ◽

Other Hand ◽

Pulmonary Vasodilator ◽

The Relationship

Background:Connective tissue disease-associated pulmonary hypertension (CTD-PH) is constructed by a variety of pathologies, including cardiac, pulmonary, and vascular involvement, as well as immune abnormalities. Because of its various constructs, it is difficult for many respiratory physicians, cardiologists, and rheumatologists to determine a treatment strategy for CTD-PH. In addition, CTD-PH has different pathologies from iPAH, and there are cases in which immunosuppressive therapy is effective. These suggests that the two PAHs may have different pathogenesis, including inflammation in the pulmonary artery. However, there are not enough biomarkers to distinguish pathologies. On the other hand, it has been reported that various cytokines such as TIMP-1, Interleukin (IL)-6, IL-17, and IL-21 are involved in the pathogenesis of CTD-PH or vasculitis. (1,2) However, the relationship between these cytokine expression and the pathogenesis or treatment of CTD-PH has not been fully clarified.Objectives:To clarify the relationship between cytokine profile and clinical features, change in cytokines and hemodynamics by treatment, association with the effectiveness of immunosuppressive therapy.Methods:Patients suspected PH was included. At the time of cardiac catheterization(RHC), sera in pulmonary pre and post-capillary were collected and TIMP-1, MCP-1, IL-17 and IL-21, IL-12p70 and IL-6 were analyzed by ELISA(ABCAM UK, Ella simple plex USA). The following clinical data were collected: age, gender, underlying disease, complication of interstitial lung disease, treatment (immunosuppressant and pulmonary vasodilator), hemodynamics. Furthermore, we investigated the relationship between cytokines and clinical data.Results:15 cases of CTD-PH, 13 cases of non-CTD-PH, and 6 cases of non-PH were analyzed. (SSc 12 cases, MCTD 7cases, SLE 2 cases, and others 13 cases) 28 cases were diagnosed with PH by RHC. There was a positive correlation between IL-6 and mean pulmonary arterial pressure in all PH case. In addition, MCP-1, IL-6, and TIMP-1 tend to be high in SSc-PH cases. On the other hand, in Non-SSc-PH, IL-12p70 and IL-17 were high. In cases who pulmonary vascular hemodynamics improved by treatment, IL-17, IL-21, and TIMP-1 decreased.Conclusion:Biomarker profiles in pulmonary capillaries may differ depending on the disease. Furthermore, it suggested that IL-17, IL-21 and TIMP-1 may be biomarkers of therapeutic effect.References:[1]Hashimoto-Kataoka T. et al. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2677-86.[2]Jun Ishizaki et al. Arthritis Res Ther. 2017 Sep 29;19(1):218.Disclosure of Interests:None declared.

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Evolution of cardiac function in COVID 19 patients in the intensive care unit: insights from machine learning

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.431 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

P Marti Castellote ◽

F Loncaric ◽

M Nogueira ◽

M Sitges ◽

B Stessel ◽

...

Keyword(s):

Machine Learning ◽

Pulmonary Hypertension ◽

Intensive Care ◽

Cardiac Function ◽

Diastolic Dysfunction ◽

Diastolic Function ◽

Clinical Data ◽

Cardiac Cycle ◽

Doppler Velocity ◽

Output Space

Abstract Funding Acknowledgements Type of funding sources: None. Background Repeated echocardiographic assessment of cardiac function is integral in management of intensive care units (ICU) patients. Machine learning (ML) can assist by integrating whole-cardiac cycle echo data derived from flow assessment and deformation imaging, and grouping patients on the basis of patterns of cardiac dysfunction and its evolution over time. Cardiac involvement has been suggested to be important in COVID-19 outcome and echo evaluation can inform on cardiac status. We use unsupervised ML to investigate and integrate longitudinal data from the COVID-HO study (NCT04371679) to determine the potential of tracking changes in cardiac function during ICU hospitalization. Methods In a single-centre, COVID-19 patients (n = 38) were prospectively followed with echocardiography as part of ICU management. The endpoint was defined as death or ICU discharge. LV myocardial deformation, as well as aortic, mitral and pulmonary artery blood-pool Doppler velocity profiles were used as input for ML. Clinical data was used to validate the ML derived phenotypes. Echo data from the initial and final echo examination were used to create an output space where participants were positioned based on cardiac function blinded to outcome status. Regression was used to estimate the echo and clinical characteristics of different regions in the space. Patient trajectories in the output space were investigated for each patient. Results Endpoint was not reached in 24% (n = 9) at the time of analysis. The cohort was 68% male, aged 65 ± 12 years, and with an ICU mortality 21% (n = 8). The median spent in ICU was 10 (IQR 7-18) days. The ML analysis demonstrated a heterogeneous output space (Fig 1A) we could define a gradual change in the shape of the pulmonary outflow velocity profile, from a normal towards pulmonary hypertension (Fig 1A, x axis). Jointly with differences in diastolic function (mitral inflow fusion and A wave accentuation) defined two regions: with signs of pulmonary hypertension (gray); and with normal pulmonary pressures but LV diastolic dysfunction (yellow). Investigation of patient trajectories (Fig 1B) demonstrated the feasibility of tracking changes during ICU hospitalization, showing a shift of a patient that died in the ICU, from initial diastolic dysfunction towards pulmonary hypertension (red), and a patient shifting from a region with normal diastolic function towards pulmonary hypertension, but with a positive outcome (blue). Echo data concurs with observed dynamics (Fig 1C and 1D). Conclusion ML can integrate complex, whole-cardiac cycle echo data to group heterogeneous patients based on similarity of cardiac function. Patient trajectories across the output space demonstrate the feasibility of ML for echo data-based follow-up of patients during ICU hospitalization. Further echo and clinical data integration can improve characterisation of the output space regions and better define changes in cardiac function during hospitalization. Abstract Figure 1

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Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder

Cardiovascular Psychiatry and Neurology ◽

10.1155/2009/278531 ◽

2009 ◽

Vol 2009 ◽

pp. 1-7 ◽

Cited By ~ 53

Author(s):

Hadar Shalev ◽

Yonatan Serlin ◽

Alon Friedman

Keyword(s):

Blood Brain Barrier ◽

Clinical Data ◽

Molecular Mechanisms ◽

Neurovascular Unit ◽

Animal Experiments ◽

Network Connectivity ◽

Brain Barrier ◽

Local Inflammatory Response ◽

Blood Brain ◽

And Behavior

The mechanisms underlying the development and progression of psychiatric illnesses are only partially known. Clinical data suggest blood-brain barrier (BBB) breakdown and inflammation are involved in some patients groups. Here we put forward the “BBB hypothesis” and abnormal blood-brain communication as key mechanisms leading to neuronal dysfunction underlying disturbed cognition, mood, and behavior. Based on accumulating clinical data and animal experiments, we propose that events within the “neurovascular unit” are initiated by a focal BBB breakdown, and are associated with dysfunction of brain astrocytes, a local inflammatory response, pathological synaptic plasticity, and increased network connectivity. Our hypothesis should be validated in animal models of psychiatric diseases and BBB breakdown. Recently developed imaging approaches open the opportunity to challenge our hypothesis in patients. We propose that molecular mechanisms controlling BBB permeability, astrocytic functions, and inflammation may become novel targets for the prevention and treatment of psychiatric disorders.

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Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography

Journal of Applied Physiology ◽

10.1152/japplphysiol.00890.2002 ◽

2003 ◽

Vol 94 (4) ◽

pp. 1543-1551 ◽

Cited By ~ 107

Author(s):

George M. Balanos ◽

Nicholas P. Talbot ◽

Keith L. Dorrington ◽

Peter A. Robbins

Keyword(s):

Pulmonary Hypertension ◽

Pressure Gradient ◽

Doppler Echocardiography ◽

Time Course ◽

Vascular Tone ◽

Animal Experiments ◽

Vascular Response ◽

Circulatory Response ◽

Breathing Control ◽

End Tidal

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po 2 = 100 Torr) hypercapnia (end-tidal Pco 2 was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco 2 was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1–2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco 2. The human pulmonary circulatory response to changes in Pco 2 has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial.

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