Pulmonary Vascular Bed Research Articles

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Hipertensión pulmonar. Aclarando conceptos

Pulmonary Arterial Hypertension is a central syndrome produced by a large number of cardiological, pulmonary, and systemic diseases that affect the lung bed. It is defined by the existence of a pulmonary artery systolic pressure greater than 30 or a mean pressure greater than 25 mmHg. This definition criterion has been maintained for more than 60 years. However, the current classification includes two concepts: a Pulmonary Arterial Hypertension (PAH) with two groups of disorders in which only pulmonary arterial resistance increases and five groups that are classified as Pulmonary Hypertension (PH): PH Secondary to Pulmonary Veno-occlusive Disease , HP secondary to diseases of the left side of the heart; HP Obliterative diseases and pulmonary hypoxemia; HP Pulmonary thrombus occlusive diseases, and a group of multifactorial HP. The difference is found in how the different diseases affect the pulmonary vascular bed, and how they alter the physiology or behavior of pulmonary resistance, which are the concepts that must be handled when talking about this syndrome and whose structural changes and management we will discuss in a later article.

АНГИОПУЛЬМОНОГРАФИЯ С НИТРОГЛИЦЕРИНОВЫМ ТЕСТОМ В ДИАГНОСТИКЕ ОСТРЫХ ИНФЕКЦИОННЫХ ДЕСТРУКЦИЙ ЛЕГКИХ

Objective. To develop a method for additional and differential diagnosis of acute infectious lung destruction (AILD) based on angiopulmonography with the nitroglycerin test. Methods. Angiopulmonography with the nitroglycerin test was used in 10 patients with suppurative diseasesof thelung and pleura for additional and differential diagnosis of AILD The method was used in such situations when chest computed tomography did not allow to determine unambiguously the presence and / or prevalence of necrosis of the lung parenchyma. Results. In 3 patients with the lung abscess, a clear restriction of the decay cavity was registered with the preservation of the main blood flow and weakening of the parenchymal phase of the blood circulation along the periphery of the destructive area. During the nitroglycerin test performance there was no change in the filling of the microvascular bed with contrast along the periphery of the decay cavity, which made it possible to determine the presence of parietal sequesters. According to the results of the study, the lung gangrene was diagnosed in 6 patients. At the same time, two variants of circulatory disorders were noted: the first - with preservation of the blood flow through the main vessels and with the absence of a parenchymal phase in the lesion focus, the second - with the violation of the main blood flow. In the affected area no change in blood flow was observed after the nitroglycerin test performance. Similar results of the study indicated the development of necrosis of the pulmonary parenchyma, which was subsequently confirmed during the operations performed. In the site of inflammatory infiltration of the pulmonary parenchyma with preserved main blood flow, the depletion of the parenchymal phase of blood circulation was determined, but after the nitroglycerin test, a pronounced enrichment of the vascular architecture to the parenchymal phase in the pneumonia affecting part of the lung was noted. Conclusion. It has been established that AILD is characterized by irreversible changes in the vascular bed of the lung parenchyma in the lesion focus. Angiopulmonography with the nitroglycerin test is considered to be an additional highly informative method improving the early and differential diagnosis of AILD in difficult clinical situations. What this paper adds It has been found out that during angiopulmonography the areas of pulmonary necrosis are characterized by the absence of a vascular pattern with or without disturbance of the blood flow through the segmental arteries. At the same time, in contrast to the foci of pneumonia, the nitroglycerin test is not accompanied by an evaluation of the filling of the pulmonary vascular bed in the affected area, i.e. blood supply disorders are irreversible. Thus, based on an assessment of the nature and reversibility of the blood flow disturbances in the affected lung, it is possible to carry out differential diagnosis of the early stages of acute infectious lung destruction (AILD) and pneumonia.

The pulmonary vascular bed in patients with functionally univentricular physiology and a Fontan circulation.

Fontan palliation represents one of the most remarkable surgical advances in the management of individuals born with functionally univentricular physiology. The operation secures adult survival for all but a few with unfavourable anatomy and/or physiology. Inherent to the physiology is passive transpulmonary blood flow, which produces a vulnerability to adequate filling of the systemic ventricle at rest and during exertion. Similarly, the upstream effects of passive flow in the lungs are venous congestion and venous hypertension, especially marked during physical activity. The pulmonary vascular bed has emerged as a defining character on the stage of Fontan circulatory behaviour and clinical outcomes. Its pharmacologic regulation and anatomic rehabilitation therefore seem important strategic therapeutic targets. This review seeks to delineate the important aspects of pulmonary artery development and maturation in functionally univentricular physiology patients, pulmonary artery biology, pulmonary vascular reserve with exercise, and pulmonary artery morphologic and pharmacologic rehabilitation.

Single-cell transcriptomic profile of human pulmonary artery endothelial cells in health and pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is an insidious disease characterized by severe remodeling of the pulmonary vasculature caused in part by pathologic changes of endothelial cell functions. Although heterogeneity of endothelial cells across various vascular beds is well known, the diversity among endothelial cells in the healthy pulmonary vascular bed and the pathologic diversity among pulmonary arterial endothelial cells (PAEC) in PAH is unknown and previously unexplored. Here single-cell RNA sequencing technology was used to decipher the cellular heterogeneity among PAEC in the human pulmonary arteries isolated from explanted lungs from three patients with PAH undergoing lung transplantation and three healthy donor lungs not utilized for transplantation. Datasets of 36,368 PAH individual endothelial cells and 36,086 healthy cells were analyzed using the SeqGeq bioinformatics program. Total population differential gene expression analyses identified 629 differentially expressed genes between PAH and controls. Gene Ontology and Canonical Ingenuity analysis revealed pathways that are known to be involved in pathogenesis, as well as unique new pathways. At the individual cell level, dimensionality reduction followed by density based clustering revealed the presence of eight unique PAEC clusters that were typified by proliferative, angiogenic or quiescent phenotypes. While control and PAH harbored many similar subgroups of endothelial cells, PAH had greater proportions of angiogenic and proliferative subsets. These findings identify that only specific subgroups of PAH PAEC have gene expression different than healthy PAEC, and suggest these subpopulations lead to the pathologic functions leading to remodeling.

Case report on the management of failed tunneled hemodialysis catheter insertion

Hemodialysis vascular access is critical to ensuring adequate hemodialysis sessions. Tunneled internal jugular vascular (IJV) access is a type of intermediate access that has become increasingly useful in low- and middle-income countries, where there are not many vascular surgeons with expertise in arteriovenous fistula creation. We presented a 69-year-old male who had complicated IJV catheter insertion, with the catheter located in the pulmonary vascular bed of the left lung and associated left-sided hemothorax. He was managed by multidisciplinary team of nephrologists, radiologists, and cardiothoracic surgeons, who removed the catheter under fluoroscopic guidance without any complication or need for open thoracotomy. The case highlighted the utility of fluoroscopy in aiding hemodialysis catheter insertion, removal, and management of its complications.

COVID-19 ARDS Is Characterized by Increased Dead Space Ventilation Compared With Non-COVID ARDS.

ARDS in patients with coronavirus disease 2019 (COVID-19) is characterized by microcirculatory alterations in the pulmonary vascular bed, which could increase dead-space ventilation more than in non-COVID-19 ARDS. We aimed to establish if dead-space ventilation is different in patients with COVID-19 ARDS when compared with patients with non-COVID-19 ARDS. A total of 187 subjects with COVID-19 ARDS and 178 subjects with non-COVID-19 ARDS who were undergoing invasive mechanical ventilation were included in the study. The association between the ARDS types and dead-space ventilation, compliance of the respiratory system, subjects' characteristics, organ failures, and mechanical ventilation was evaluated by using data collected in the first 24 h of mechanical ventilation. Corrected minute ventilation (V˙E), a dead-space ventilation surrogate, was higher in the subjects with COVID-19 ARDS versus in those with non-COVID-19 ARDS (median [interquartile range] 12.6 [10.2-15.8] L/min vs 9.4 [7.5-11.6] L/min; P < .001). Increased corrected V˙E was independently associated with COVID-19 ARDS (odds ratio 1.24, 95% CI 1.07-1.47; P = .007). The best compliance of the respiratory system, obtained after testing different PEEPs, was similar between the subjects with COVID-19 ARDS and the subjects with non-COVID-19 ARDS (mean ± SD 38 ± 11 mL/cm H2O vs 37 ± 11 mL/cm H2O, respectively; P = .61). The subjects with COVID-19 ARDS received higher median (interquartile range) PEEP (12 [10-14] cm H2O vs 8 [5-9] cm H2O; P < .001) and lower median (interquartile range) tidal volume (5.8 [5.5-6.3] mL/kg vs 6.6 [6.1-7.3] mL/kg; P < .001) than the subjects with non-COVID-19 ARDS, being these differences maintained at multivariable analysis. In the multivariable analysis, the subjects with COVID-19 ARDS showed a lower risk of anamnestic arterial hypertension (odds ratio 0.18, 95% CI 0.07-0.45; P < .001) and lower neurologic sequential organ failure assessment score (odds ratio 0.16, 95% CI 0.09-0.27; P < .001) than the subjects with non-COVID-19 ARDS. Indirect measurements of dead space were higher in subjects with COVID-19 ARDS compared with subjects with non-COVID-19 ARDS. The best compliance of the respiratory system was similar in both ARDS forms provided that different PEEPs were applied. A wide range of compliance is present in every ARDS type; therefore, the setting of mechanical ventilation should be individualized patient by patient and not based on the etiology of ARDS.

Viewpoint: Time to stop treating the heart as a single organ?

All too often, when physiologists and clinicians speak of the ‘the heart’, they are referring to the left side of the heart. A PubMed search completed in March 2021 reveals nearly an equal number of publications about the left and right ventricles (136,338 vs. 121,010, respectively). Nonetheless, in physiology and medical education, we teach cardiovascular physiology from the perspective of the left ventricle, with a nod to the fact that the right ventricle is structurally different and experiences different systolic pressures. Our references to ‘cardiac physiology’ when we mean ‘left ventricular physiology’ might perpetuate the misconception that the physiology we discover in the left ventricle is directly translatable to the right. It should not be surprising that the right and left ventricles respond differently to stress. They have different embryonic origins and patterns of development (Tan & Lewandowski, 2020). They are, indeed, anatomically dissimilar throughout the lifespan, have different metabolic requirements and supply structurally different vasculatures. In this issue of Experimental Physiology, Silva et al. (2021) reinforce the importance of evaluating the right and left ventricular responses to stress separately in a model of moderate, short-term alcohol consumption. The major finding of this work is that only 4 weeks of alcohol consumption caused remodelling of the pulmonary vascular bed, increased right ventricular systolic pressure and right ventricular hypertrophy. The right ventricle and pulmonary vasculature both showed increased protein expression related to tissue remodelling and evidence of oxidative stress. In contrast, the left ventricle was largely unaffected. As most provocative papers do, this manuscript raises as many questions as it answers. Is right ventricular hypertrophy the result of increased pulmonary vascular resistance in this model, or does ethanol drive parallel responses in the ventricle and vasculature that result in remodelling? Given that experiments were performed in male rats only, we wonder about sex differences (Shansky & Murphy, 2021). There is sexual dimorphism in the development of pulmonary hypertension (Zemskova et al., 2020). Male patients with pulmonary hypertension have more markers of necrosis and inflammation in the arterial wall, whereas female patients display more markers of apoptosis resistance and proliferation. Would these sex differences also be evident in this model? Given our own interests in early life events and cardiopulmonary development (Bates et al., 2020), we also cannot help but wonder about the impact of age on these intriguing differences between the right and left ventricular responses to ethanol. Would early life exposure have a durable impact on the development of the right ventricle? Are the effects of ethanol reversible in this model? What are the consequences of chronic exposure, and which ventricle fails first? As the authors point out in their discussion, we now have data for only two conditions at single time points: their moderate exposure model, in which the effects on the right ventricle precede the left ventricle, and an excessive consumption model, in which both the right and left ventricles are impaired. This paper made us wonder about the longitudinal impact of consumption on right and left ventricular function. Would we have asked the same number of questions if the authors had focused only on the right ventricle and had not also examined the left ventricle? This paper highlights the importance of future exploration and continued rationale to study the right heart as an organ that responds to stresses in a different manner from the left heart. We look forward to continued research in this area and thought-provoking discussions that arise when groups are careful to evaluate physiological responses in both the right and left ventricles. None declared.

Therapeutically Targeting Microvascular Leakage in Experimental Hemorrhagic SHOCK: A Systematic Review and Meta-Analysis.

Microvascular leakage is proposed as main contributor to disturbed microcirculatory perfusion following hemorrhagic shock and fluid resuscitation, leading to organ dysfunction and unfavorable outcome. Currently, no drugs are available to reduce or prevent microvascular leakage in clinical practice. We therefore aimed to provide an overview of therapeutic agents targeting microvascular leakage following experimental hemorrhagic shock and fluid resuscitation. PubMed, EMBASE.com, and Cochrane Library were searched in January 2021 for preclinical studies of hemorrhagic shock using any therapeutic agent on top of standard fluid resuscitation. Primary outcome was vascular leakage, defined as edema, macromolecule extravasation, or glycocalyx degradation. Drugs were classified by targeting pathways and subgroup analyses were performed per organ. Forty-five studies, published between 1973 and 2020, fulfilled eligibility criteria. The included studies tested 54 different therapeutics mainly in pulmonary and intestinal vascular beds. Most studies induced trauma besides hemorrhagic shock. Forty-four therapeutics (81%) were found effective to reduce microvascular leakage, edema formation, or glycocalyx degradation in at least one organ. Targeting oxidative stress and apoptosis was the predominantly effective strategy (SMD: -2.18, CI [-3.21, -1.16], P < 0.0001). Vasoactive agents were found noneffective in reducing microvascular leakage (SMD: -0.86, CI [-3.07, 1.36], P = 0.45). Pharmacological modulation of pathways involved in cell metabolism, inflammation, endothelial barrier regulation, sex hormones and especially oxidative stress and apoptosis were effective in reducing microvascular leakage in experimental hemorrhagic shock with fluid resuscitation. Future studies should investigate whether targeting these pathways can restore microcirculatory perfusion and reduce organ injury following hemorrhagic shock. CRD42018095432.

Usefulness of ischemia-modified albumin for assessment of the effects of small ventricular septal defects on the pulmonary vascular bed.

Pulmonary vascular damage may be associated with oxidative stress in congenital heart diseases. We investigated whether small ventricular septal defects have an effect on the pulmonary bed. This prospective cohort study included 100 patients with small ventricular septal defects and 75 healthy controls. Ischemia-modified albumin, high-sensitivity C-reactive protein, and various cardiovascular parameters were assessed in both groups. The mean ischemia-modified albumin level was significantly higher in patients with small ventricular septal defects (0.62 ± 0.17 absorbance units) than in the control group (0.51 ± 0.09 absorbance units; p < 0.001). The mean high-sensitivity C-reactive protein level was significantly higher in the ventricular septal defects group (3.72 ± 1.57) than in the control group (2.45 ± 0.89; p < 0.001). The ischemia-modified albumin levels in patients with left ventricular internal diameter end diastole and end sistole and main pulmonary artery z-scores ≥ 2 were significantly higher than patients whose z-scores were <2. The ischemia-modified albumin and high-sensitivity C-reactive protein levels were positively correlated in the small ventricular septal defects group (rho = 0.742, p < 0.001). Receiver operating characteristic analyses showed that at the optimal cut-off value of ischemia-modified albumin for the prediction of pulmonary involvement was 0.55 absorbance units with a sensitivity of 60%, specificity of 62% (area under the curve = 0.690, p < 0.001). We demonstrated the presence of oxidative stress and higher ischemia-modified albumin levels in small ventricular septal defects, suggesting that ischemia-modified albumin might be a useful biomarker for evaluating the effects of small ventricular septal defects on the pulmonary bed.

High CD200 Expression on T CD4+ and T CD8+ Lymphocytes as a Non-Invasive Marker of Idiopathic Pulmonary Hypertension–Preliminary Study

Pulmonary arterial hypertension (PAH) can develop subsequently to disorganized endothelial cell proliferation within the pulmonary arteriolar layers that provide mechanical limits to the pulmonary vascular bed. Although the actual factor triggering vascular endothelial proliferation remains unknown to date, genetic susceptibility, hypoxia, inflammation, as well as response to drugs and toxins have been proposed as possible contributors. Since inflammation contributes to vascular remodeling, the changed immune response is increasingly considered a plausible cause of this cardiovascular disease. The interaction of a membrane glycoprotein cluster of differentiation 200 (CD200) and its structurally similar receptor (CD200R) plays a crucial role in the modulation of the inflammatory response. Our previous studies have shown that the overexpression of the other negative co-stimulatory molecule (programmed death cell-PD-1) and its ligand-1 (PD-L1) is closely related to iPAH and the presence of Epstein-Barr virus (EBV) reactivation markers. Therefore, we considered it necessary to analyze the different types of PAH in terms of CD200 and CD200R expression and to correlate CD200/CD200R pathway expression with important clinical and laboratory parameters. The CD200/C200R-signaling pathway has not been subject to much research. We included 70 treatment-naïve, newly diagnosed patients with PAH in our study. They were further divided into subsets according to the pulmonary hypertension classification: chronic thromboembolic pulmonary hypertension (CTEPH) subset, pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH), and idiopathic pulmonary arterial hypertension (iPAH). The control group consisted of 20 healthy volunteers matched for sex and age. The highest percentages of T CD200+CD4+ and T CD200+CD8+ lymphocytes were observed in the group of patients with iPAH and this finding was associated with the presence of EBV DNA in the peripheral blood. Our assessment of the peripheral blood lymphocytes expression of CD200 and CD200R indicates that these molecules act as negative co-stimulators in the induction and persistence of PAH-associated inflammation, especially that of iPAH. Similar results imply that the dysregulation of the CD200/CD200R axis may be involved in the pathogenesis of several immune diseases. Our work suggests that CD200 and CD200R expression may serve to distinguish between PAH cases. Thus, CD200 and CD200R might be useful as markers in managing PAH and should be further investigated.

To Unifocalize or Not to Unifocalize?: A Comparison of Retroesophageal Versus Anterior Collaterals

BackgroundThe anatomy of major aortopulmonary collateral arteries (MAPCAs) can be highly variable with regard to number, anatomic origin, course, and relationship to the native pulmonary arteries. Some MAPCAs travel behind the esophagus (retroesophageal) and bronchus before entering the lung parenchyma. This study compared the physiologic and surgical characteristics of retroesophageal vs anterior located MAPCAs. MethodsThis was a retrospective review of 42 patients who had 1 (n = 36) or 2 (n = 6) retroesophageal MAPCAs. These MAPCAs were then characterized as (1) single supply, meaning no connection to the pulmonary arteries; (2) dual supply, but inadequate connection to the distal pulmonary vascular bed; and (3) dual supply with adequate connection. ResultsThe 42 patients presented with 187 MAPCAs, or 4.5 MAPCAs per patient. Of these, 48 MAPCAs were retroesophageal, including 40 that were single supply, 6 were dual supply with inadequate connection, and 2 had dual supply with adequate connection. On the basis of this anatomy and physiology, 96% of retroesophageal MAPCAs were unifocalized. For the 139 anterior MAPCAs, 89 were single supply, 15 were dual supply with inadequate connection, and 35 were dual supply with adequate connection; thus, 75% of anterior MAPCAs were unifocalized (P < .01 compared with retroesophageal MAPCAs). ConclusionsThe data demonstrate that retroesophageal MAPCAs had very different anatomy and physiology compared with anterior MAPCAs. These results suggest that nearly every retroesophageal MAPCA should be unifocalized to incorporate the lung segments supplied.

Peripheral microangiopathy\xa0in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study

BackgroundAlthough pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity.MethodsΑ prospective case–control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal–Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test).ResultsBoth IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 μm and 15.8 ± 1.9 μm vs. 11.5 ± 2.3 μm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001).ConclusionThe findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

The pathophysiology and complications of Fontan circulation.

The Fontan operation has been the final palliation for patients born with congenital heart defects with a functional single ventricle for more than 4 decades. The “normal” Fontan physiology is characterized by the loss of the sub-pulmonary ventricle with consequent elevated pressure in the caval system, non-pulsatile blood flow in the pulmonary circulation and at least mild reduction of the systemic output. When successful, this procedure is associated with a range of benefits including improved arterial saturation and abolishment of chronic volume overload, allowing a fairly normal life to the majority of patients through early adulthood. As we enter the 5th decade of caring for patients palliated with the Fontan procedure, it is evident that adult survivors face significant morbidity due to multiorgan dysfunction, early mortality and need for heart transplantation. Several late complications may occur: ventricular dysfunction, arrhythmia, cyanosis, exercise intolerance, elevated pulmonary vascular resistance, protein-losing enteropathy, plastic bronchitis, hepatic and renal complications. The mechanism of late Fontan failure is multifactorial and not completely understood, it depends on interactions between the ventricle, the pulmonary vascular bed, the venous and lymphatic compartments.Conclusions:the aim of this review is to describe the pathophysiology of Fontan circulation and the clinical and hemodynamic characteristics of early and late failing Fontan survivors, their association with morbidity and mortality, and the strategies for their management. (www.actabiomedica.it).

Pulmoner Endarterektomi Operasyonlarında Anestezi ve Komplikasyonların Yönetimi

Objective: Chronic thromboembolic pulmonary hypertension is a chronic progressive disease developing obstruction ocurring in pulmonary vascular bed. Pulmonary endarterectomy is the surgical procedure described in the management of chronic pulmonary hypertension which excises, and removes the obstructing thromboembolic material from the affected vascular structures. Our aim is to share our approaches to the management of anesthesia and complications in pulomanry endarterectomy operations performed in our center. Methods: The data of 200 PEA cases conducted in June 2017-2020 were retrospectively analyzed. The demographic data of the patients, preoperative pulmonary function tests, cardiac catheterization findings, peroperative cardiac output measurement values, aortic cross clamp, extubation, intensive care unit, and hospital stay times and complications were recorded. Results: Average age of the patients’ ages was 50.8 years, and female/male ratio was 108/92. In the thermodilution measurements of the patients after induction, mean values of CO, PVR and mPAP were determined as 4.4 l/min, 594 dyn/s/cm-5, 40 mmHg, respectively. The corresponding measurements made after the sternal closure were stated as 6 l/min, 241 dyn/s/cm-5 and 28 mmHg, respectively. The patients were hospitalized in the intensive care unit for 4 days. In our patient group residual pulmonary hypertension occurred in 21%, reperfusion pulmonary edema in 10% and pulmonary bleeding in 4% of the cases. Conclusion: Only a very few centers in the world are experienced in PEA surgery. Anesthesia management and treatment of the complications of PEA surgery are quite difficult. Therefore, PEA surgery shl be performed in experienced centers.

Spontaneous fibrinolysis and possibilities of its acceleration in pulmonary embolism

This review contains the data concerning the mechanisms of spontaneous fibrinolysis in pulmonary vessels and possibilities of its acceleration in pulmonary embolism. The spontaneous fibrinolysis system is known to be sequential and multifactorial, with the interaction of accelerators (t-PA and u-PA) and inhibitors (alpha-2-antiplasmin, PAI-1, TAFI). The fibrinolytic processes take place in case of prevailing reactions of accelerating factors over inhibiting ones. The endothelium of pulmonary vessels possesses pronounced antithrombogenic and profibrinolytic properties, therefore, the processes of fibrinolysis in the pulmonary vascular bed normally occur more intensively than in the vessels of the systemic circulation. The membrane proteins of the endothelium annexins A2 activate plasminogen, whereas thrombomodulin inhibits the activity of PAI-1. The main approaches to increase the fibrinolysis intensity in conditions of pulmonary embolism may be aimed at elevating the activity of fibrinolytic enzymes (enhancing the synthesis of annexins A2, the use of NMDA-receptor antagonists) and suppressing its inhibitors (the use of monoclonal antibodies to alpha-2-antiplasmin, as well as plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI). Promising directions for future research can be the synthesis of a new generation of tissue-type plasminogen activators, and investigations of the possibility of clinical application of antithrombin and thrombomodulin, angiotensin converting enzyme inhibitors and cortisol antagonists. To meet these challenges, it is necessary to develop new models of venous thrombosis and acute pulmonary embolism in different animal species, with the assessment of the changes in the venous haemodynamics and pulmonary microcirculation on the background of administration of a new class of fibrinolytic agents.

Pulmonary Covid Fibrosis a New Pharmaceutic Approach.

Background:Patient's post-COVID may develop chronic irreversible respiratory failure with “widespread signs of pulmonary fibrosis.” Our study analyzed the causes of this fibrosis to propose a therapeutic protocol.Methods:Identification of the biochemical causes of fibrosis in COVID-19 analysing the literature and chest CT.Results:The CT imaging shows pulmonary fibrosis. The viral infection produces “interleukin-6”, which binds to its receptor, in MUC1 of lung epithelial cells. The biochemical response of the cells promotes an over-expression of MUC1 with fibrosis. Interleukin6 also causes a metabolic imbalance in NO that promotes clots and atherosclerosis of the pulmonary vessels. These results show to promote NO endothelia's formation to block both the excessive expression of MUC1 and the atherosclerosis effect of the vessels.Conclusions:This study proposes to inhibit phosphodiesterase by vasodilatation of the pulmonary vascular bed and the MUC1 over expression by interleukin6, the Sildenafil with the SGLT2 and N-Acetylcysteine.

Thrombotic Lesion of the Pulmonary Vessels in Patients with Pulmonary Embolism

After suffering pulmonary embolism (PE), doctors are confronted with various consequences of the disease, from asymptomatic residual pulmonary thrombosis to the formation of chronic thromboembolic pulmonary hypertension (CTEPH). There is also a subgroup of patients who have undergone pulmonary embolism, who experience shortness of breath during physical exertion, absent before pulmonary embolism, or shortened dyspnea preceding PE, combined with residual thrombosis of pulmonary artery (PA) and normal average pressure in PA at rest during catheterization of the right heart (CRH). This condition is defined as chronic thromboembolic pulmonary disease or post thromboembolic syndrome. Pathogenetic aspects of this condition are not fully investigated. It is important to predict the development of postembolic syndrome and to develop algorithms for the diagnosis, treatment and rehabilitation of patients with symptoms and residual pulmonary thrombosis. In case of the development of pulmonary vasculopathy in some patients who have undergone pulmonary embolism, a severe life-threatening condition forms - CTEPH, characterized by an increase in pressure in the pulmonary artery, right heart failure due to the presence of organized blood clots that have entered the pulmonary vascular bed during PE. The volume of thrombotic masses does not always correlate with clinical symptoms, which indicates the importance of microvascular remodeling. If CTEPH is suspected, a diagnostic algorithm is required, including ventilation-perfusion scintigraphy, CT angiopulmonography and catheterization of the right heart. Treating a patient with CTEPH is a difficult task fora doctor. The timely referral of the patient to the center where they are involved in treatment, including surgery and CTEPH is extremely important. Timely performed thrombendarterectomy in some cases allows to completely cure the patient. In the case of inoperable CTEPH or residual pulmonary hypertension after thrombendarterectomy, balloon angioplasty of the PA is used as well as drug treatment with specific drugs that reduce the pressure in the PA (riociguat), endothelin receptor antagonists (bosentan, macitentan), prostanoids (inhalant illoprost) phosphodiesterase-5 inhibitor and combined therapy. In this article we considered some consequences directly related to PE: asymptomatic residual pulmonary thrombosis, chronic thromboembolic pulmonary disease, chronic thromboembolic pulmonary hypertension.

Endocan as a potential biomarker of disease severity and exacerbations in COPD.

Endocan is a proteoglycan that is regarded as a novel marker of endothelial dysfunction. Endothelial dysfunction in pulmonary vascular bed is known to play an important role for the pathogenesis of COPD. This study aimed to determine serum endocan levels in patients with stable COPD and acute exacerbation of COPD (AECOPD) and to test the relationship between serum endocan levels and exacerbations. This study enrolled a total of 55 COPD patients, 24 of which had AECOPD and 31 had stable COPD. All patients' basic demographic and clinical data were recorded and blood samples were collected. Serum endocan levels were significantly higher in the AECOPD group compared to the stable COPD and control groups (for both p<0.001) and stable COPD group had higher levels than the control group (p<0.005). Additionally, serum endocan levels were negatively correlated with FVC, FEV1, partial oxygen pressure and oxygen saturation (r=-0.30, p=0.03; r=-0.34, p=0.01; r=-0.34, p=0.01 and r=-0.36, p=0.007 respectively), and positively correlated with disease duration and systolic pulmonary artery pressure (r=0.47, p<0.001; r=0.31, p=0.02 respectively). A cut-off value of 434.29pg/ml for endocan predicted exacerbation with a sensitivity of 79% and a specificity of 84% (AUC: 0.778, 95% Cl 0.648-0.909; p<0.001). Logistic regression analysis revealed that increased endocan levels was independent predictor of COPD exacerbation (OR=9.32, 95%CI, 1.64-52.95; p=0.01). Endocan may be a novel biomarker for detection of endothelial dysfunction and prediction of exacerbations in patients with COPD.