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Pulmonary Circulation Apr 2024
PubMed: 38939305
DOI: 10.1002/pul2.12408 -
Pulmonary Circulation Apr 2024Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the... (Review)
Review
Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso-responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model-based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.
PubMed: 38933181
DOI: 10.1002/pul2.12392 -
Pulmonary Circulation Apr 2024Pollution and climate change constitute a combined, grave and pervasive threat to humans and to the life-support systems on which they depend. Evidence shows a strong... (Review)
Review
Pollution and climate change constitute a combined, grave and pervasive threat to humans and to the life-support systems on which they depend. Evidence shows a strong association between pollution and climate change on cardiovascular and respiratory diseases, and pulmonary vascular disease (PVD) is no exception. An increasing number of studies has documented the impact of environmental pollution and extreme temperatures on pulmonary circulation and the right heart, on the severity and outcomes of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH), on the incidence of pulmonary embolism, and the prevalence and severity of diseases associated with PH. Furthermore, the downstream consequences of climate change impair health care systems' accessibility, which could pose unique obstacles in the case of PVD patients, who require a complex and sophisticated network of health interventions. Patients, caretakers and health care professionals should thus be included in the design of policies aimed at adaptation to and mitigation of current challenges, and prevention of further climate change. The purpose of this review is to summarize the available evidence concerning the impact of environmental pollution and climate change on the pulmonary circulation, and to propose measures at the individual, healthcare and community levels directed at protecting patients with PVD.
PubMed: 38933180
DOI: 10.1002/pul2.12394 -
Frontiers in Medicine 2024The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in...
INTRODUCTION
The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia.
METHODS
Prior to conception, carunclectomy surgery was performed on non-pregnant ewes to induce FGR. At 108-110 days (d) gestational age (GA), pregnant ewes bearing control ( = 12) and FGR ( = 9) fetuses underwent fetal catheterisation surgery. At 117-119 days GA, ewes underwent MRI sessions where phase-contrast (PC) and T oximetry were used to measure blood flow and oxygenation, respectively, throughout the fetal circulation during a normoxia and then an acute hypoxia state.
RESULTS
Fetal oxygen delivery (DO) was lower in FGR fetuses than controls during the normoxia state but cerebral DO remained similar between fetal groups. Acute hypoxia reduced both overall fetal and cerebral DO. FGR increased ductus venosus (DV) and foramen ovale (FO) blood flow during both the normoxia and acute hypoxia states. Pulmonary blood flow (PBF) was lower in FGR fetuses during the normoxia state but similar to controls during the acute hypoxia state when PBF in controls was decreased.
CONCLUSION
Despite a prevailing level of chronic hypoxaemia, the FGR fetus upregulates the preferential streaming of oxygen-rich blood via the DV-FO pathway to maintain cerebral DO. However, this upregulation is unable to maintain cerebral DO during further exposure to an acute episode of hypoxaemia. The haemodynamic alterations required at the level of the liver and lung to allow the DV-FO pathway to maintain cerebral DO, may have lasting consequences on hepatic function and pulmonary vascular regulation after birth.
PubMed: 38933113
DOI: 10.3389/fmed.2024.1340012 -
Journal of Clinical Medicine Jun 2024There was increased risk of mental disturbances during the COVID-19 pandemic. Patients with chronic diseases, including pulmonary arterial hypertension (PAH) and...
Anxiety and Depression in Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension after the Removal of COVID-19 Pandemic Restrictions.
There was increased risk of mental disturbances during the COVID-19 pandemic. Patients with chronic diseases, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), were particularly vulnerable. Our previous study showed high levels of fear of COVID-19 (FCV-19S), anxiety (HADS-A), and depression (HADS-D) in the second year of the pandemic among PAH/CTEPH patients. The aim of the present study was to assess changes in the levels of FCV-19S, HADS-A, and HADS-D after removing restrictions related to the COVID-19 pandemic. In this prospective, single-center study, 141 patients (62% females, 64% PAH) with a median age of 60 (range 42-72) years were included. Patients completed appropriate surveys in the second year of the pandemic, and then, after the restrictions were lifted in Poland (after 28 March 2022). FVC-19S decreased significantly from 18 (12-23) to 14 (9-21), < 0.001. The levels of anxiety (HADS-A ≥ 8 points) and depression (HADS-D ≥ 8 points) were abnormal in 26% and 16% of patients, respectively; these did not change at follow-up ( = 0.34 for HADS-A and = 0.39 for HADS-D). : Among PAH/CTEPH patients, fear of COVID-19 decreased significantly after the COVID-19 pandemic restrictions were removed, but anxiety and depression remained high, indicating that the COVID-19 pandemic was not a major factor in causing these disorders.
PubMed: 38930062
DOI: 10.3390/jcm13123532 -
Journal of Clinical Medicine Jun 2024Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of... (Review)
Review
Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant.
PubMed: 38929946
DOI: 10.3390/jcm13123417 -
Journal of Clinical Medicine Jun 2024The association of obesity with right ventricular function and the interplay between right heart and pulmonary circulation is incompletely understood. We evaluate the...
The association of obesity with right ventricular function and the interplay between right heart and pulmonary circulation is incompletely understood. We evaluate the role of obesity as a determinant of right ventricular-pulmonary artery coupling (RVAC). We retrospectively studied consecutive subjects without overt cardiovascular or pulmonary disease. Subjects were stratified according to body mass index (BMI) as normal weight, overweight, or obese. A transthoracic echocardiographic study was used to assess left and right heart functional and structural parameters. RVAC was assessed using the ratio of peak systolic velocity of the tricuspid annulus to pulmonary artery systolic pressure (PASP). A total of 145 subjects were enrolled with diabetes mellitus incidence higher in obese. There was no difference in left ventricular global longitudinal strain and in PASP or markers of right ventricular systolic function based on BMI. RVAC was significantly lower in the presence of obesity (normal weight: 0.52 (0.19) cm·(sec·mmHg) vs. overweight: 0.47 (0.16) cm·(sec·mmHg) vs. obese: 0.43 (0.14) cm·(sec·mmHg), = 0.03), even after adjustment for confounders (β: -0.085, 95% confidence interval: -0.163, -0.009, = 0.029). Our findings highlight the relationship between metabolic impairment and RVAC, suggesting additional mechanisms for heart failure development observed in obese subjects.
PubMed: 38929919
DOI: 10.3390/jcm13123389 -
Bioengineering (Basel, Switzerland) Jun 2024Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary...
Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary arteries. Our purpose was to investigate whether increasing inferior vena cava (IVC) flow with a rotary blood pump in the IVC only in an ovine animal model of Fontan would lead to acceptable superior vena cava (SVC) pressure. To achieve this, a Fontan circulation was established in four female sheep by anastomosing the SVC to the main pulmonary artery (MPA) and by interposing a Dacron graft between the IVC and the MPA. A rotary blood pump was then introduced in the graft, and the effect of incremental flows was observed at increasing flow regimen. Additionally, to stimulate increased pulmonary resistance, the experience was repeated in each animal with the placement of a restrictive band on the MPA distally to the SVC and Dacron graft anastomosis. Circulatory support of IVC flow alone increased the systemic cardiac output significantly, both with and without banding, indicating the feasibility of mechanical support of the Fontan circulation by increasing the flow only in the inferior vena cava. The increase in SVC pressure remained within acceptable limits, indicating the potential effectiveness of this mode of support. The findings suggest that increasing the flow only in the inferior vena cava is a feasible method for mechanical support of the Fontan circulation, potentially leading to an increase in cardiac output with acceptable increases in superior vena cava pressure.
PubMed: 38927830
DOI: 10.3390/bioengineering11060594 -
Use of FRET-Sensor 'Mermaid' to Detect Subtle Changes in Membrane Potential of Primary Mouse PASMCs.Cells Jun 2024Subtle changes in the membrane potential of pulmonary arterial smooth muscle cells (PASMCs) are pivotal for controlling pulmonary vascular tone, e.g., for initiating...
Subtle changes in the membrane potential of pulmonary arterial smooth muscle cells (PASMCs) are pivotal for controlling pulmonary vascular tone, e.g., for initiating Hypoxic Pulmonary Vasoconstriction, a vital mechanism of the pulmonary circulation. In our study, we evaluated the ability of the fluorescence resonance energy transfer (FRET)-based voltage-sensor Mermaid to detect such subtle changes in membrane potential. Mouse PASMCs were isolated and transduced with Mermaid-encoding lentiviral vectors before the acceptor/donor emission ratio was assessed via live cell FRET-imaging. Mermaid's sensitivity was tested by applying specific potassium chloride (KCl) concentrations. These KCl concentrations were previously validated by patch clamp recordings to induce depolarization with predefined amplitudes that physiologically occur in PASMCs. Mermaid's emission ratio dose-dependently increased upon depolarization with KCl. However, Mermaid formed unspecific intracellular aggregates, which limited the usefulness of this voltage sensor. When analyzing the membrane rim only to circumvent these unspecific signals, Mermaid was not suitable to resolve subtle changes in the membrane potential of ≤10 mV. In summary, we found Mermaid to be a suitable alternative for reliably detecting qualitative membrane voltage changes of more than 10 mV in primary mouse PASMCs. However, one should be aware of the limitations associated with this voltage sensor.
Topics: Animals; Fluorescence Resonance Energy Transfer; Membrane Potentials; Mice; Myocytes, Smooth Muscle; Pulmonary Artery; Potassium Chloride; Mice, Inbred C57BL
PubMed: 38920698
DOI: 10.3390/cells13121070 -
European Heart Journal. Case Reports Jun 2024Fontan surgery aims to palliate univentricular congenital heart diseases in which biventricular repair is not feasible. A large spectrum of early and late complications...
BACKGROUND
Fontan surgery aims to palliate univentricular congenital heart diseases in which biventricular repair is not feasible. A large spectrum of early and late complications has been described in literature. However, pulmonary thromboembolism represents a rare complication in these patients, leading to a scarcity of evidence regarding diagnosis and treatment strategies.
CASE SUMMARY
We present a case of a 27-year-old woman born with a complex cyanotic congenital heart disease, namely pulmonary and tricuspid stenosis with subaortic interventricular communication and atrial septal defect, who underwent palliation surgery with Blalock-Taussig shunt, bidirectional Glenn, and extracardiac Fontan. She developed acute respiratory failure and was admitted to the hospital, being diagnosed with bilateral thromboembolism. Since she was haemodynamically stable, initially, a conservative approach was chosen. However, due to no clinical improvement, she subsequently underwent bilateral thromboaspiration with restoration of pulmonary circulation.
DISCUSSION
Due to the unique Fontan pathophysiology, the possible physiological and clinical implications of pulmonary thromboembolism in this condition are profound. Thus, care and imaging tests in specialized centres are important as the management of these patients is different from those with biventricular physiology.
PubMed: 38915741
DOI: 10.1093/ehjcr/ytae190