Pulmonary Vascular Bed Research Articles

Cigarette Smoke Directly Promotes Pulmonary Arterial Remodeling and Kv7.4 Channel Dysfunction.

Rationale: Cigarette smoke is considered the chief leading cause of chronic obstructive pulmonary disease (COPD). Its impact on the progressive deterioration of airways has been extensively studied, but its direct effects on the pulmonary vasculature are less known. Objectives: To prove that pulmonary arterial remodeling in patients with COPD is not just a consequence of alveolar hypoxia but also due to the direct effects of cigarette smoke on the pulmonary vascular bed. Methods: We have used different molecular and cell biology approaches, as well as traction force microscopy, wire myography, and patch-clamp techniques in human cells and freshly isolated pulmonary arteries. In addition, we relied on invivo models and human samples to analyze the effects of cigarette smoke on pulmonary vascular tone alterations. Measurements and Main Results: Cigarette smoke extract exposure directly promoted a hypertrophic, senescent phenotype that in turn contributed, through the secretion of inflammatory molecules, to an increase in the proliferative potential of nonexposed cells. Interestingly, these effects were significantly reversed by antioxidants. Furthermore, cigarette smoke extract affected cell contractility and dysregulated the expression and activity of the voltage-gated K+ channel Kv7.4. This contributed to the impairment of vasoconstriction and vasodilation responses. Most importantly, the levels of this channel were diminished in the lungs of smoke-exposed mice, smokers, and patients with COPD. Conclusions: Cigarette smoke directly contributes to pulmonary arterial remodeling through increased cell senescence, as well as vascular tone alterations because of diminished levels and function in the Kv7.4 channel. Strategies targeting these pathways may lead to novel therapies for COPD.

High Prevalence of Persistent Breathlessness Following Sub-Massive Pulmonary Embolism in Patients Presenting to a Large Regional Hospital in South Wales.

There is a broad literature exploring the investigation, treatment, management and outcomes of patients suffering from pulmonary embolism (PE). Chronic thromboembolic pulmonary hypertension (CTEPH) has been studied but less is known about outcomes for the large majority of individuals surviving PE who do not have persistent thrombus or CTEPH. Radiology, hospital and primary care records were reviewed in patients with central pulmonary emboli presenting to a large hospital in South Wales between 2013-16. 2501 CTPA were reviewed. 380 (15.2%) showed PE and of these 127 (33.4%) involved the main pulmonary arteries or the pulmonary trunk. 4 patients received systemic and 1 catheter directed thrombolysis. 16 (12.6%) patients died of PE during the admission. Excluding patients dying within 3 months, 49 patients (48.5%) were more SOB than before the pulmonary embolus (73.7 % if there was evidence of right heart strain during admission). Of these 6 patients (12.2%) had evidence of persisting PE and/or pulmonary hypertension. In patients with no evidence of persisting clot or pulmonary hypertension where full lung function was performed there was an isolated reduction in gas transfer measurement (mean TLCO 57%). Many patients remain breathless following large volume PE particularly if there is evidence of Right ventricular strain at presentation. The pathophysiology is unclear but lung function testing is consistent with persisting damage to the pulmonary vascular bed. These findings may allow clinicians to better advise patients of expected outcomes following major pulmonary embolus and may avoid unnecessary further investigation.

Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation

The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period.MethodsThis explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland.ResultsForty-six women with a singleton pregnancy greater than or equal to 31 weeks’ gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT.ConclusionThese findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

Abstract 14367: Abnormal Pulmonary Flow is Associated With Impaired Right Ventricular Coupling in Patients With COPD

Introduction: Cor Pulmonale or right ventricular (RV) dysfunction due to pulmonary disease is an expected complication of COPD resulting from increased afterload mediated by hypoxic pulmonary vasoconstriction as well as the destruction of the pulmonary vascular bed. Early detection of elevated RV afterload has been previously demonstrated by visualization of abnormal flow patterns in the proximal pulmonary arteries. Prior quantitative analysis of helicity in the pulmonary arteries of pulmonary hypertension patients has demonstrated a strong association between helicity and increased RV afterload. Hypothesis: Patients with COPD will have abnormal pulmonary flow as evaluated by 4D-Flow MRI and associated with RV function and pulmonary arterial stiffness. Methods: Patients with COPD (n=15) (65yrs ± 6) and controls (n=10) (58yrs ± 9) underwent 4D-Flow MRI to calculate helicity (Figure 1A). The helicity was calculated in 2 segments: 1) the main pulmonary artery (MPA) and 2) along the RV outflow tract (RVOT) - MPA axis. Main pulmonary arterial stiffness was measured using the relative area change (RAC). Results: COPD patients had decreased helicity relative to healthy controls in the MPA (19.4±7.8 vs 32.8±15.9 s -2 , P=0.007) (Figure 1B). Additionally, COPD patients had reduced helicity along the RVOT-MPA axis (33.2±9.0 vs 43.5±8.3 s -2 , P=0.010). The helicity measured in the MPA was associated with RV end-systolic volume (R=0.59, P = 0.002), RVEF (R=0.631, P&lt;0.001), RAC (R=-0.61, P=0.001). e combined helicity along the MPA-RVOT axis was associated with RVEF (R=0.74, P&lt;0.001), RVESV (R=-0.57, P=0.004), and RAC (R=0.42, P=0.005). Conclusion: Patients with COPD show quantitatively abnormal flow hemodynamics, when compared with healthy controls, as assessed by 4D-Flow MRI. A strong association between helicity along the MPA-RV outflow tract axis and RV function suggests that 4D-Flow MRI might be a sensitive tool in evaluating RV - pulmonary arterial coupling in COPD.

Extracellular matrix collagen biomarkers levels in patients with chronic thromboembolic pulmonary hypertension.

Limited data exist on changes in the extracellular matrix (ECM) collagen biomarkers levels during chronic thromboembolic pulmonary hypertension (CTEPH) development. This study aimed to investigate ECM collagen biomarkers levels in stable patients with CTEPH. Patients with CTEPH and healthy persons were enrolled. Serum levels of procollagen III N-terminal peptide (PIIINP), carboxyterminal propeptide of type I procollagen (PICP), matrix metalloproteinases (MMP2), MMP9, and tissue inhibitor of metalloproteinases 1(TIMP1) were measured by ELISA. Clinical data coincident with samples were collected. The pulmonary endarterectomy (PEA) and control pulmonary artery tissue samples were analyzed for genetic and immunohistochemical differences. The serum concentrations of PIIINP, PICP, MMP2, and MMP9 decreased significantly in CTEPH patients compared to healthy controls (P < 0.001 for each). CTEPH patients had higher serum concentrations of TIMP1 (median, 111.97 [interquartile range, 84.35-139.93]) compared to healthy controls (74.97 [44.03-108.45] ng/mL, P < 0.001). The MMP2 to TIMP1 ratio was lower in patients than in the controls (P < 0.001). After adjusting for the body mass index (BMI), the MMP2 to TIMP1 ratio correlated negatively with pulmonary vascular resistance (PVR) (r = - 0.327, P = 0.025). Increased TIMP1 (P = 0.04) gene expression was identified in tissues of CTEPH patients. Immunohistochemistry results of vascular walls substantiated qRT-PCR results. This study indicates that ECM collagen biomarkers levels were significantly different in stable patients with CTEPH and healthy controls with significantly increased TIMP1 and decreased MMP2 and MMP9. Differences in TIMP1 expression should be expected not only among healthy controls and patients serum, but also across pathological tissue regions. These findings suggest that the state of vascular remodeling in pulmonary vascular bed in stable patients may be represented by ECM collagen biomarkers levels. We conclude that TIMP1 may play an important role in pulmonary vascular reconstruction in stable CTEPH patients.

The effects of genetic deletion of Macrophage migration inhibitory factor on the chronically hypoxic pulmonary circulation.

While it is well established that the haemodynamic cause of hypoxic pulmonary hypertension is increased pulmonary vascular resistance, the molecular pathogenesis of the increased resistance remains incompletely understood. Macrophage migration inhibitory factor is a pleiotropic cytokine with endogenous tautomerase enzymatic activity as well as both intracellular and extracellular signalling functions. In several diseases, macrophage migration inhibitory factor has pro-inflammatory roles that are dependent upon signalling through the cell surface receptors CD74, CXCR2 and CXCR4. Macrophage migration inhibitory factor expression is increased in animal models of hypoxic pulmonary hypertension and macrophage migration inhibitory factor tautomerase inhibitors, which block some of the functions of macrophage migration inhibitory factor, and have been shown to attenuate hypoxic pulmonary hypertension in mice and monocrotaline-induced pulmonary hypertension in rats. However, because of the multiple pathways through which it acts, the integrated actions of macrophage migration inhibitory factor during the development of hypoxic pulmonary hypertension were unclear. We report here that isolated lungs from adult macrophage migration inhibitory factor knockout (MIF–/–) mice maintained in normoxic conditions showed greater acute hypoxic vasoconstriction than the lungs of wild type mice (MIF+/+). Following exposure to hypoxia for three weeks, isolated lungs from MIF–/– mice had significantly higher pulmonary vascular resistance than those from MIF+/+ mice. The major mechanism underlying the greater increase in pulmonary vascular resistance in the hypoxic MIF–/– mice was reduction of the pulmonary vascular bed due to an impairment of the normal hypoxia-induced expansion of the alveolar capillary network. Taken together, these results demonstrate that macrophage migration inhibitory factor plays a central role in the development of the pulmonary vascular responses to chronic alveolar hypoxia.

Systemic-to-Pulmonary Collateral Flow Correlates with Clinical Condition Late After the Fontan Procedure.

In the Fontan circulation, there is a substantial degree of systemic-to-pulmonary collateral flow (SPCF), which can be measured by cardiac magnetic resonance (CMR). However, the correlation between the degree of SPCF and long-term outcomes is not fully understood. We retrospectively studied 321 patients who underwent the Fontan procedure and CMR at a single center. Using CMR, we calculated SPCF as pulmonary blood flow - systemic blood flow. %SPCF was defined as SPCF ÷ pulmonary blood flow. The mean age of patients at CMR was 14.3 ± 7.5years. The average %SPCF was 13.0% ± 11.0%. With a multivariate analysis, %SPCF was significantly correlated with time (i.e., the longer the time period since the Fontan procedure, the lower the %SPCF) (p = 0.006), previous total anomalous pulmonary vein drainage (p = 0.007), a low pulmonary artery index (Nakata index) before the Fontan procedure (p = 0.04), and older age at the time of the Fontan procedure (p = 0.002). Regarding the findings after the Fontan procedure, %SPCF was significantly correlated with ventricular end-diastolic volume (p < 0.001), ventricular end-systolic volume (p < 0.001), central venous pressure (p < 0.001), plasma brain natriuretic peptide concentration (p < 0.001), hemoptysis (p = 0.009), and poor New York Heart Association functional class (p = 0.007). SPCF was correlated with clinical condition after the Fontan procedure. The importance of sufficient growth of the pulmonary vascular bed should be emphasized because the development of SPCF is believed to result from the poor condition of the pulmonary circulation.

Effects of angiotensin receptor neprilysin inhibition on pulmonary arterial stiffness in heart failure with reduced ejection fraction.

The sacubitril/valsartan combination is an important agent used in the treatment of heart failure with reduced ejection fraction (HFrEF). Pulmonary artery stiffness (PAS) is an index developed to evaluate the pulmonary vascular bed. Changes in pulmonary vascular structures in HFrEF patients can affect PAS. In this study, we aimed to investigate the effect of sacubitril/valsartan on PAS in HFrEF patients. One hundred fifty HFrEF patients, who received sacubitril/valsartan therapy and continued for at least 6months without interruption, were examined retrospectively. N-terminal pro-B-type natriuretic peptide levels (NT-proBNP), NYHA classes, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores, New York Heart Association (NYHA) functional classes and echocardiograpic parameters such as left ventricular ejection fraction (LVEF), mean pulmonary artery pressure (mPAP), right ventricle myocardial performance index (RV-MPI), Tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RV-FAC) and PAS changes were evaluated before and 6months after sacubitril/valsartan treatment. PAS was calculated by using the maximal frequency shift and acceleration time of the pulmonary artery flow trace measured in the echocardiogram. PAS values were significantly reduced (23.8 ± 2.8 vs 19.1 ± 3.1kHz/ms, p < 0.001) after the sacubitril/valsartan treatment. Sacubitril/valsartan treatment was associated with significant improvements in NYHA class and MLWHFQ scores; significant reductions in the NT-proBNP levels, mPAP, and RV-MPI, and significant increases in LVEF, TAPSE, and RV-FAC (p < 0.05). The significant reduction in the PAS value was significantly correlated with the improvements in the MLWFQ scores, NT-proBNP levels, mPAP, RV-MPI, TAPSE and RV-FAC. In HFrEF patients, switching from angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy to sacubitril/valsartan may result in reduction in PAS.

A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions.

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by profound vascular remodeling in which pulmonary arteries narrow because of medial thickening and occlusion by neointimal lesions, resulting in elevated pulmonary vascular resistance and right heart failure. Therapies targeting the neointima would represent a significant advance in PAH treatment; however, our understanding of the cellular events driving neointima formation, and the molecular pathways that control them, remains limited. We comprehensively map the stepwise remodeling of pulmonary arteries in a robust, chronic inflammatory mouse model of pulmonary hypertension. This model demonstrates pathological features of the human disease, including increased right ventricular pressures, medial thickening, neointimal lesion formation, elastin breakdown, increased anastomosis within the bronchial circulation, and perivascular inflammation. Using genetic lineage tracing, clonal analysis, multiplexed in situ hybridization, immunostaining, deep confocal imaging, and staged pharmacological inhibition, we define the cell behaviors underlying each stage of vascular remodeling and identify a pathway required for neointima formation. Neointima arises from smooth muscle cells (SMCs) and not endothelium. Medial SMCs proliferate broadly to thicken the media, after which a small number of SMCs are selected to establish the neointima. These neointimal founder cells subsequently undergoing massive clonal expansion to form occlusive neointimal lesions. The normal pulmonary artery SMC population is heterogeneous, and we identify a Notch3-marked minority subset of SMCs as the major neointimal cell of origin. Notch signaling is specifically required for the selection of neointimal founder cells, and Notch inhibition significantly improves pulmonary artery pressure in animals with pulmonary hypertension. This work describes the first nongenetically driven murine model of pulmonary hypertension (PH) that generates robust and diffuse occlusive neointimal lesions across the pulmonary vascular bed and does so in a stereotyped timeframe. We uncover distinct cellular and molecular mechanisms underlying medial thickening and neointima formation and highlight novel transcriptional, behavioral, and pathogenic heterogeneity within pulmonary artery SMCs. In this model, inflammation is sufficient to generate characteristic vascular pathologies and physiological measures of human PAH. We hope that identifying the molecular cues regulating each stage of vascular remodeling will open new avenues for therapeutic advancements in the treatment of PAH.

Rethinking COVID-19 'pneumonia' - is this primarily a vaso-occlusive disease, and can early anticoagulation save the ventilator famine?

Rethinking COVID-19 'pneumonia' - is this primarily a vaso-occlusive disease, and can early anticoagulation save the ventilator famine?

Pulmonary intravascular coagulopathy in COVID-19 pneumonia.

Pulmonary intravascular coagulopathy in COVID-19 pneumonia.

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.

SummaryThe lung pathology seen in patients with coronavirus disease 2019 (COVID-19) shows marked microvascular thrombosis and haemorrhage linked to extensive alveolar and interstitial inflammation that shares features with macrophage activation syndrome (MAS). We have termed the lung-restricted vascular immunopathology associated with COVID-19 as diffuse pulmonary intravascular coagulopathy, which in its early stages is distinct from disseminated intravascular coagulation. Increased circulating D-dimer concentrations (reflecting pulmonary vascular bed thrombosis with fibrinolysis) and elevated cardiac enzyme concentrations (reflecting emergent ventricular stress induced by pulmonary hypertension) in the face of normal fibrinogen and platelet levels are key early features of severe pulmonary intravascular coagulopathy related to COVID-19. Extensive immunothrombosis over a wide pulmonary vascular territory without confirmation of COVID-19 viraemia in early disease best explains the adverse impact of male sex, hypertension, obesity, and diabetes on the prognosis of patients with COVID-19. The immune mechanism underlying diffuse alveolar and pulmonary interstitial inflammation in COVID-19 involves a MAS-like state that triggers extensive immunothrombosis, which might unmask subclinical cardiovascular disease and is distinct from the MAS and disseminated intravascular coagulation that is more familiar to rheumatologists.

Microencapsulation of small extracellular vesicles with nanoporous biomaterials results in a sustained-release preparation to enhance targeting and persistence after intravascular delivery

Background & Aim Mesenchymal stromal cells (MSCs) have shown promise as therapy for treatment of cardiovascular disease. The therapeutic effect of MSCs is predominately paracrine, involving the release of small ( Methods, Results & Conclusion MSC-derived small EVs were collected during 24h of serum-free culture and purified using sequential ultracentrifugation or tangential flow filtration. ZetaView nanoparticle tracking revealed a population of small EVs having a median size of 108±53 nm, positive for the tetraspanin CD63 by Western blot analysis. Pkh26 membrane labelling of small EVs had negligible impact on EV size (median size 102±42 nm). Agarose (2%) or agarose-gelatin (1%-1%) microgels were formed using vortex-emulsion or microfluidic encapsulation, resulting microgels of differing size (34±15 mm and 59±3 mm, respectively). Free EVs, EV-loaded microgels, or empty microgels were plated with human umbilical vein endothelial cells (HUVEC) and time-lapse imaging over 48h demonstrated transfer of EVs from microgels to HUVEC. While by 48h free EVs were readily taken up by HUVECs, encapsulated EVs demonstrated a slower uptake during this period (64% vs 26% cells/FOV), consistent with sustained release kinetics. Biodegradability of microgels was assessed in vivo using the rat monocrotaline (MCT) model of pulmonary arterial hypertension. Three days post MCT empty microgels were delivered by intrajugular injection. Right ventricular systolic pressure was assessed at day 1, 3 and 7. IV delivery of 500,000 agarose-gelatin or agarose microgels had no impact on right ventricular systolic pressure compared to vehicle (saline). Gelatin-agarose microgels demonstrated >2-fold more rapid degradation and clearance from the pulmonary vascular bed from day 1 through to day 7 post compared with agarose microgels. Microencapsulation of small EVs in nanoporous biomaterials produces microgels which are efficiently trapped in the microcirculation with tunable release of EVs depending on biomaterial composition and gel degradation rate.

Hemodynamic Instability in Hypoxic Ischemic Encephalopathy: More Than Just Brain Injury-Understanding Physiology, Assessment, and Management.

Hypoxic-ischemic encephalopathy (HIE) can have both transient and long-lasting effects on the neonate, including neurologic, renal, cardiac, hepatic, and hematologic. Both the disease process and the treatment option of therapeutic hypothermia can result in hemodynamic instability. Understanding the effects of HIE on the neonatal myocardium, pulmonary vascular bed, and the cardiac dysfunction that can occur is key to managing infants with HIE. This article focuses on causes of hemodynamic instability in neonates following perinatal asphyxia and how to recognize hemodynamic compromise. It reviews the underlying pathophysiology and associated management strategies to improve hemodynamics and potentially improve outcomes.

Evaluation of Lung Quality by Near-Infrared Fluorescent Imaging during Ex Vivo Lung Perfusion

Improved real-time assessment of donor lung quality during Ex Vivo Lung Perfusion (EVLP) could enhance safe utilization of lungs for transplantation. Near-infrared (NIR) fluorescent imaging with indocyanine green (ICG) has been used in various clinical intraoperative applications to evaluate tissue perfusion. We investigated the feasibility of NIR imaging during EVLP and aimed to detect and quantify lung perfusion and permeability. Pig lungs with extended 24-hour cold ischemia (n=4) and human lungs rejected from clinical transplantation (n=2) were assessed with NIR imaging during EVLP. Serial NIR imaging was performed with SPY Elite imaging system after ICG (0.3, 0.6 or 1.0 mg) administration through pulmonary artery (Fig A). Tissue perfusion was quantified using SPYQ analysis software, and tissue ICG accumulation was correlated with lung damage. Strong NIR signal was detected immediately after ICG administration with 0.6 mg (pig lungs) or 1.0 mg (human lungs) doses resulting in optimal fluorescence for tissue perfusion evaluation. In contrast to the transient kinetics and fast liver metabolism during clinical in vivo ICG administration, a single ICG dose during EVLP resulted in stable NIR signal for over 10 hours. Perfusion quantification of pig lungs with extended cold preservation revealed peripheral areas with compromised tissue perfusion that gradually recovered over time with recruitment of additional pulmonary vascular beds (Fig B). ICG accumulation was detected in sites with damage and increased vascular permeability in pig and human lungs (Fig C and D). NIR imaging with a clinically-approved intravascularly-delivered ICG fluorescent probe can dynamically quantify tissue perfusion and detect damage-induced vascular permeability. This novel and promising imaging modality could be used during EVLP to assess lung quality, or to determine effects of therapeutics that target tissue perfusion and vascular permeability.

Characteristics of Pulmonary Vascular Remodeling in a Porcine Model of Shunt-Associated Pulmonary Arterial Hypertension.

Lung biopsy is the gold standard for evaluating pathological changes in the pulmonary vascular bed. Knowing the distribution characteristics of pulmonary vascular lesions can improve the accuracy of lung biopsy. To investigate the distribution characteristics of pulmonary vascular remodeling, a reliable porcine model of shunt-associated pulmonary arterial hypertension (PAH) was established. Twenty piglets were randomly divided into the experimental group (n = 10) and the control group (n = 10). A modified Blalock-Taussig shunt (MBTS, left innominate artery to main pulmonary artery) was created surgically in the experimental group. Three months later, an invasive catheter was used to obtain hemodynamic parameters, and lung biopsy was performed to assess the remodeling of pulmonary vascular bed. MBTS was successfully implemented in six piglets. There's no significant difference in hemodynamic parameters of the two groups before the shunt. However, these parameters and right ventricular hypertrophy index of the experimental group were significantly increased after three months shunting. Pathological changes in the experimental group, including thickening of pulmonary artery media, intimal fibrosis, and right ventricular hypertrophy, were observed. Furthermore, the percentage of media thickness and medial area of the experimental group were significantly higher than control group. Histopathology showed that vascular remodeling of the lung was inhomogeneous and that the lateral lesion was more severe than other segments. These results indicated that MBTS could be used to establish a reliable porcine model of shunt-associated PAH and that multisite detection with different segments should be applied to assess the severity of pulmonary vascular remodeling.

Echocardiographic Evaluation of Right Ventricular Function and its Role in the Prognosis of Chronic Obstructive Pulmonary Disease.

Background:Chronic obstructive pulmonary disease (COPD) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload and subsequently right heart failure.Objectives:The aim of the study was to elucidate RV dysfunction at rest by echocardiography in a cohort of COPD patients and to study its impact on prognosis.Methods:84 patients of COPD and 40 matching healthy controls were evaluated at baseline. Evaluation included clinical examination, pulmonary function tests; 6 minutes walk test and echocardiography. Patient with COPD were again evaluated after 6 months.Results:All echocardiographic parameters of RV function were significantly impaired in COPD patients as compared to controls. Clinical deterioration in COPD group was much more in patients with baseline abnormal RV function (89%) and patients with RV systolic pressure ≥35 mmHg (P = 0.018). All the six patients who died had three or more abnormal RV systolic function parameters.Conclusions:RV myocardial performance index and basal strain showed largest difference between controls and COPD cases. Clinical deterioration was more common in patients with abnormal RV function parameters and pulmonary hypertension.

Single-shot thoracic epidural analgesia for neonates undergoing thoracotomy.

ABSTRACT Background and Aims: Post-thoracotomy pain in neonates have negative physiological consequences include impaired ventilation and vasoconstriction of both systemic and pulmonary vascular beds leading to compromised organ function. Methods: A randomized, single center, prospective, controlled study was conducted in El-Shatby university hospital, from august 2017 to September 2019 were 40 neonates, weighing 2.5–4 kg belonging to the ASA physical Grade II to IV, posted for a trachea-oesophagal fistula (TOF) repair via thoracotomy. After general anesthesia, in Group A, intra-operatively received fentanyl 2 µg/kg and paracetamol (10 mg/kg/6 h) intravenously and Group B (thoracic epidural single injection with 0.5 ml/kg of 0.25% of the L-Bupivacaine and 2 µg/kg of fentanyl), postoperatively paracetamol (10 mg/kg/6 h) intravenous (IV) or pain score >4. The primary objective was to compare the effect of the single-shot epidural blockade to intravenous fentanyl on post-thoracotomy pain control, the length of stay (LOS), supplemental analgesic requirements, and the incidence of adverse respiratory events were also measured. Results: Group A remained hemodynamically stable in the intraoperative period except for occasional bradycardia below 100 which was successfully managed with anticholinergic, and multiple and regular dosage of IV paracetamol was required to maintain adequate analgesia for about 6 h post-operative. While in Group B, good quality of analgesia for 8 h post-operative with a lesser dose of rescue opioids (fentanyl) required to maintain adequate analgesia which shortened length of hospital stay. Conclusion: Very efficient postoperative analgesia can be achieved via single-shot epidural blockade compared to intravenous fentanyl in neonatal post-thoracotomy pain.

Primary Central Pulmonary Artery Plasty for Ductal-Associated Pulmonary Artery Coarctation

Infants with functionally single ventricle who require a modified Blalock-Taussig shunt can have stenosis at the ductal insertion site on the pulmonary artery (PA), the so-called ductal-associated PA coarctation. We hypothesized that central PA plasty with resection of the ductal tissue on the PA during the first palliation would prevent PA coarctation and obtain well-balanced PA for Fontan operation. We performed this strategy on 40 consecutive patients (from 1998 to 2012, Age 38.4 ± 24.7 day [17 neonates], body weight 3.5 ± 0.8 kg, heterotaxy n = 27). The mean Nakata index (mm2/m2) before bidirectional cavopulmonary shunt was 230.7 ± 101.7 without pulmonary stenosis. The PA diameter ratio and lung perfusion ratio (nonshunt side and/or shunt side) were 0.93 ± 0.25 and 0.9 ± 0.2, respectively. This strategy may improve clinical outcomes on functional single ventricle patients with increased risk of stenosis from pulmonary coarctation, with avoidance of an unbalanced pulmonary vascular bed.

P1515 Hemodynamic determinants of tricuspid annular pulmonary systolic excursion (TAPSE)/ systolic pulmonary arterial pressure (SPAP) ratio in Heart Failure with reduced Ejection Fraction

Abstract Background the TAPSE/SPAP ratio has gained a role as an easy-to-use surrogate of right ventricle-to-pulmonary circulation (RV-PC) coupling, showing a strong prognostic significance in heart failure (HF) patients. The hemodynamic determinants of TAPSE/SPAP ratio, as assessed by invasive approach, have not been fully clarified. Aim To identify the right heart hemodynamic variables correlated with TAPSE/SPAP in a HF with reduced EF (HFrEF) cohort, both at rest and during exercise. Methods 30 HFrEF patients (age 68 ± 10 years LV EF 28 ± 7) underwent to rest and exercise echocardiography and performed right heart catheterization within 24 hours. Bivariate correlations between TAPSE/SPAP ratio (at rest and during exercise), right heart hemodynamic variables, RV systolic function and NTproBNP have been explored. Results TAPSE/SPAP ratio at rest showed a moderate correlation with pulmonary artery wedge pressure (PAWP: r= 0.441; p= 0.039), pulmonary artery pressures (PAP systolic: r = 0.481; p= 0.026; PAP diastolic: r= 0.434; p= 0.043; mPAP: r= 0.476; p= 0.025), pulmonary vascular resistance and compliance (r= 0.475; p= 0.041). A stronger correlation was identified with right atrial (RAP systolic: r= 0.586; p= 0.017; RAP diastolic: r= 0.681; p= 0.006) and right ventricular pressures- in particular diastolic ones (RVP systolic: r= 0.584; p= 0.004; RAP diastolic: r= 0.652; p= 0.002). No significant correlation with NTproBNP and RV 3D EF emerged. Exercise TAPSE/SPAP ratio significantly correlated with right atrium (RAP systolic: r= 0.564; p= 0.036) and right ventricle systolic pressures only (RVP systolic: r= 0.789; p&amp;lt; 0.001). Conclusions TAPSE/SPAP ratio at rest showed a stronger correlation with invasively derived diastolic right heart pressure rather than pulmonary vascular bed pressures. A similar correlation was also observed for exercise TAPSE/SPAP ratio. This tight correlation with RV, rather than with vascular pressures, supports the significance of this ratio as a marker of RV adaptation to vascular overload.