Increase In Pulmonary Arterial Pressure Research Articles

[Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension, characterized by thrombotic occlusion of the pulmonary arteries leading to vascular stenosis or obstruction, progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and eventual right heart failure. Unlike other types of pulmonary hypertension, the prognosis of CTEPH can be significantly improved by surgery, vascular intervention, and/or targeted drug therapy. Pulmonary endarterectomy (PEA) is the preferred treatment of choice for CTEPH. However, PEA is an invasive procedure with high operative risks, and is currently only performed in a few centers in China. Balloon pulmonary angioplasty (BPA) is an emerging interventional technique for CTEPH, serving as an alternative for patients who are ineligible for PEA or with residual pulmonary hypertension after PEA. BPA is gaining traction in China, but its widespread adoption is limited due to its complexity, operator skills, and equipment requirements, a lack of standard operating procedures and technical guidance, which limit the further improvement and development of BPA in China. To address this, a multidisciplinary panel of experts was convened to develop the Consensus on the Procedure of Balloon Pulmonary Angioplasty for the Chronic Thromboembolic Pulmonary Hypertension, which fomulates guidelines on BPA procedural qualification, perioperative management, procedural planning, technical approach, and complication prevention, with the aim of providing recommendations and clinical guidance for BPA treatment in CTEPH and standardizing its clinical application in this setting. Summary of recommendations: Recommendation 1: It is recommended that physicians who specialize in pulmonary vascular diseases take the lead in formulating the diagnostic and treatment plans for CTEPH, using a multidisciplinary approach.Recommendation 2: Training in BPA technique is critical; novice operators should undergo standardized operative training with at least 50 procedures under the guidance of experienced physicians before embarking on independent BPA procedures.Recommendation 3: BPA requires catheterization labs, angiography systems, standard vascular interventional devices and consumables, drugs, and emergency equipment.Recommendation 4: Patient selection for BPA should consider cardiac and pulmonary function, coagulation status, and comorbid conditions to determine indications and contraindications, thereby optimizing the timing of the procedure and improving safety.Recommendation 5: In experienced centers, patients deemed likely to benefit from early BPA, based on clinical and imaging features of CTEPH and without elevated D-dimer levels, could bypass standard 3-month anticoagulation therapy.Recommendation 6: BPA is a complex interventional treatment that requires thorough pre-operative assessment and preparation.Recommendation 7: The use of perioperative anticoagulants in BPA requires a comprehensive risk assessment of intraoperative bleeding by the operator for individualized decision making.Recommendation 8: A variety of venous access routes are available for BPA; unless contraindicated, the right femoral vein is usually preferred because of its procedural convenience and reduced radiation exposure.Recommendation 9: For the different types of vascular lesion in CTEPH, treatment of ring-like stenoses, web-like lesions, and subtotal occlusions should be prioritized before addressing complete occlusions and tortuous lesions, in order to reduce complications and improve procedural safety.Recommendation 10: A targeted, incremental balloon dilatation strategy based on vascular lesions is recommended for BPA.Recommendation 11: Intravascular pulmonary artery imaging technologies, such as OCT and IVUS can assist in accurate vessel sizing and confirmation of wire placement in the true vascular lumen. Pressure wires can be used to objectively assess the efficacy of dilatation during BPA.Recommendation 12: Endpoints for BPA treatment should be individually assessed, taking into account improvements in clinical symptoms, hemodynamics, exercise tolerance, and quality of life.Recommendation 13: Post-BPA routine monitoring of vital signs is essential; anticoagulation therapy should be initiated promptly post-procedure in the absence of complications. In cases of intraoperative hemoptysis, postoperative anticoagulation regimen adjustments should be adjusted according to the bleeding severity.Recommendation 14: If reperfusion pulmonary edema occurs during or after BPA, ensure adequate oxygenation, diuresis, and consider non-invasive positive-pressure ventilation if necessary, while severe cases may require early mechanical ventilation assistance or ECMO.Recommendation 15: In cases of intraoperative hemoptysis, temporary balloon occlusion to stop bleeding is recommended, along with protamine to neutralize heparin. Persistent bleeding may warrant the use of gelatin sponges, coil embolization, or covered stent implantation.Recommendation 16: For contrast imaging during BPA, non-ionic, low or iso-osmolar contrast agents are recommended, with hydration status determined by the patient's clinical condition, cardiac and renal function, and intraoperative contrast volume used.

Changes in the pulmonary circulation due to gravitational loads in high altitude conditions.

The impact of gravity on the existence of all living things has long been of interest to scientists. The force of the Earth's gravity combined with hypoxia significantly affects blood circulation and blood accumulation in various parts of the human and animal body. To date, the relationship between body position and blood circulation in pulmonary circulation under hypobaric hypoxia has not been sufficiently studied. Therefore, the research aims to determine the possibility of changing the body position in space on the reactions in the pulmonary circulation in the plains and highlands. For this purpose, research was conducted on male Wistar rats, 44 of whom spent 150 days at an altitude of 3200 m above sea level, and 25 representatives of the control group - at an altitude of 164 m. The study revealed that gravitational redistribution of blood in mountainous conditions is less pronounced compared to the control group. This is explained by the remodeling of the vascular wall and an increase in its stiffness. It was found that a change in pulmonary artery pressure at the time of a change in body position was recorded both on the plains and in the highlands. On the plains, when the body position of rats was changed to passive orthostatic, a decrease in systolic and diastolic pulmonary artery pressure was noted, and when the body position was changed to passive anti-orthostatic, an increase in pulmonary artery pressure was observed. The increase in pulmonary artery pressure was a compensatory mechanism due to the increased stiffness of the pulmonary vasculature. The practical significance of this research is to expand the understanding of the pathogenesis of pulmonary hypertension in high-altitude hypoxia.

Persistent iatrogenic atrial septal defect after cryoballoon ablation for atrial fibrillation

Aims: Pulmonary vein isolation (PVI) by cryoballoon ablation (CB) technology is effective and safe treatment option for atrial fibrillation (AF). CB is performed by large diameter, 15Fr (4.95mm) transseptal sheath that may lead to creation of iatrogenic atrial septal defect (iASD). The objective of this study was to assess the incidence of iASD in patients who had undergone CB. Methods: Patients with AF having undergone Arctic Front® CB ablation and a subsequent transesophageal echocardiography (TEE) examination during post-ablation follow up period were consecutively enrolled. During all CB procedures, 15Fr transseptal sheath (Flex Cath, Medtronic, Minneapolis, MN) was utilized via single transseptal puncture (TsP). Results: Twenty-eight patients (15 females, mean age 55.8+15.5) with paroxysmal (n=24) or persistent (n=4) AF formed study group. iASD was present 11 (39.3%) of them after mean follow-up time of 17.3+6.2 months. The procedural time is significantly longer in patient with iASD (119.0+8.8 minutes, p=0.01). No patients died or suffered from any clinically significant cerebral ischemic event. There was no sign of increase in systolic pulmonary arterial pressure (sPAP). Conclusion: iASD after CB was found to be present in 39.3% of patient during a mean follow-up time of 17.3+6.2 months. The prolonged CB procedural time was the only factor that predicted iASD in our study. No adverse clinic events that might be related to iASD was observed during follow-up period.

Management of Pregnant Women with Atrial Septal Defect and Pulmonary Hypertension: A Case Report

Background: Pulmonary Hypertension (PH) is a condition where there is an increase in Pulmonary Vascular Resistance (PVR) and an increase in the mean Pulmonary Arterial Pressure (mPAP) to more than 20 mmHg. PH can occur in someone with Congenital Heart Disease (CHD). PH conditions can aggravate pregnancy in women with CHD. Women with PH are recommended not to undergo pregnancy. However, it is possible for women with CHD with PH conditions to undergo pregnancy. In these conditions, optimizing PH therapy is essential so that pregnant women with PH do not experience a worsening of the condition and can carry out their pregnancy well until delivery. Case presentation: A 38-year-old female patient with a history of Atrial Septal Defect-Pulmonary Hypertension came for common control to the cardiac clinic with the pregnancy condition of her 4th child, who was just discovered when she was six months pregnant. Since giving birth to her third child, the patient began complaining of being quickly tired when doing activities accompanied by swollen legs that disappeared with rest. The patient went to a cardiologist for an echocardiography examination and was diagnosed with Atrial Septal Defect (ASD)-Pulmonary Hypertension (PH). Since then, the patient has been routinely treated by a cardiologist with Pulmonary Hypertension drugs, including Phospodiesterase5 (PDE5) inhibitors (Sildenafil) and Prostacyclin Analogue (Dorner). The patient had done Transesophageal Echocardiography (TEE) with the results of ASD secundum suitable for closure by the device. Patients with Right Heart Catheterization (RHC) results, ASD secundum with PH High Flow High Resistance reactive to Vasoreactivity Test. Since the patient was found to be pregnant, the patient continued to use Sildenafil and discontinued the use of Dorner. The patient then continued treatment in a multidisciplinary team. Conclusion: Management of pregnant women with CHD and PH is essential because the condition of PH itself further aggravates the condition of pregnancy. Medical management for PH in pregnant women follows the guidelines for the safety of drugs in pregnancy so that the choice of therapy is crucially related to the goal of treatment to control the PH condition in the patient but still pay attention to safety in pregnancy conditions. Keyword: Congenital Heart Disease, Phosphodiesterase-5 (PDE-5)- Inhibitor, Prostacyclin Analogue, Pulmonary Hypertension.

Clinical Features and Multimodality Diagnostic Tools of Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) above normal (> 20 mmHg) and an increase in pulmonary vascular resistance (pulmonary vascular resistance / PVR) above normal in resting settings. The pathophysiology of PH involves remodeling of the pulmonary vessels, from the main pulmonary arteries, lobar arteries, segmental arteries, distal arteries, pulmonary arterioles, capillaries to the postcapillary pulmonary veins. In general, the epidemiological figures for PH are not known with certainty. The United Kingdom reported a PH prevalence of 97 cases per one million people, with a female-to-male ratio of 1.8. The diagnostic strategy for PH focuses primarily on two issues. The primary objective is to improve the early detection of PH and expedite the transfer of patients at high risk for PAH, CTEPH, or other forms of severe PH to a PH center. The second objective is to identify the underlying disease, including left heart disease (Group 2 PH) and lung disease (Group 3 PH), as well as comorbidities, in order to assure proper classification, risk assessment, and therapy. The gold standard for detecting and categorizing pulmonary hypertension is right heart catheterization (RHC). Clinical scoring in the form of shortness of breath without any obvious cause accompanied by physical examination, ECG and Thorax X-ray images which depict an enlarged right heart have good specificity and sensitivity for the diagnosis of pulmonary hypertension in patients with congenital heart disease. A high right ventricular pressure, mean PAP, and BNP values during observation, as well as heart size on chest X-ray can be predictors of a poorer prognosis in this population. Keyword: Clinical Risk Scoring, Pulmonary Hypertension, Right Heart Catheterization.

Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (Organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. PA vasa vasorum are branches of the BA. The lungs were used either as control (n=3) or intervention group (n=8). The protocol of the intervention group was as follows: normoxic ventilation and perfusion (steady state) -hypoxic BA perfusion -steady state -hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady state conditions for 105 minutes. During the experiments, PA pressure (PAP) and blood gas analysis was frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible in the second hypoxic BA perfusion. Under control conditions the PAP stayed constant until about 80 minutes of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.

A mathematical model to assess the effects of COVID-19 on the cardiocirculatory system

Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia in pulmonary circulation, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19.

Current Position and Future Perspectives of Melatonin and Its Supplements in Pulmonary Hypertension

Melatonin, which is secreted principally by the pineal gland at night, affects several cardiovascular conditions including arterial hemodynamics, right ventricle functions, and pulmonary artery functions. Pulmonary hypertension is a hemodynamic and pathophysiological condition defined as an increase of average pulmonary artery pressure exceeding 20 mmHg at rest. In the light of the literature data, as discussed in this study, melatonin and its supplements may play a role in the pathogenesis and treatment of pulmonary hypertension.

Basic aspects of pathophysiology, diagnosis and treatment of patients with pulmonary arterial hypertension associated with human immunodeficiency virus infection: what has been achieved and what remains to be achieved?

Human immunodeficiency virus (HIV) infection is characterized by high morbidity and is a significant threat to human health, increasing global mortality. The number of people living with HIV infection is estimated by the United Nations Joint Program on Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (UNAIDS) to be 39 million (33.1-45.7 million) in 2022. With the introduction of highly effective antiretroviral therapy (cART) into clinical practice and the resulting increase in life expectancy in this cohort of patients, HIV-associated complications have come to the forefront, among which the most severe is pulmonary arterial hypertension (PAH), characterized by a progressive increase in pulmonary vascular resistance and pulmonary artery pressure, leading to the development of right ventricular failure. Subsequently, it became evident that this pathology can occur at all stages of HIV infection and, apparently, has no clear relationship with the degree of immunodeficiency, and is an independent predictor of mortality in patients with LAH-HIV, and therefore requires separate, close attention. This article provides an overview covering the basic pathophysiology, clinical manifestations, diagnosis and treatment of HIV-associated LAH (LAHHIV), emphasizing the challenges encountered at each stage. The review also considers current aspects aimed at studying LAH in patients with HIV, including new experimental drug therapies that take into account the interaction of different regimens with LAH-specific drugs.

The place of tadalafil in the treatment of PAH in the light of new clinical guidelines of the Eurasian Association of Cardiologists

Pulmonaryarterialhypertension(PAH)isalife-threateningcardiovascular disease that is characterized by a marked increase in pulmonary vascular resistance and pulmonary artery pressure due to obstructive remodeling of the pulmonary vascular bed with the development of right ventricular heart failure as a cause of premature mortality. Impaired synthesis and reduced bioavailability of nitric oxide is one of the key pathophysiological mechanisms of the development and progression of the disease. The review paper presents key data from the evidence base on the clinical use of tadalafil, a phosphodiesterase type 5 inhibitor (PDE5), which in August 2023 approved by the Pharmaceutical Committee of the Russian Ministry of Health for the indication – treatment of patients with PAH. Tadacardil from Canonpharma Production is the first and only drug in Russian practice today with the active substance tadalafil with the registered indication “PAH”, approved in the Eurasian Guidelines for the diagnosis and treatment of pulmonary hypertension 2023 and available on the territory of the Russian Federation and the EAEU. Tadacardil is indicated for use in adult patients with PAH functional class II and III according to the WHO classification to increase exercise tolerance. The efficacy of tadalafil has been shown in idiopathic PAH and PAH associated with connective tissue diseases. The recommended dose is 40 mg (2 tablets of 20 mg) once a day. The paper describes the mechanism of action and pharmacological effects of PDE5 inhibitors, features of the pharmacokinetics of tadalafil in comparison with other drugs of the class. The advantages of Tadacardil from Canonpharma Production are the proven effecacy of use in patients with PAH, ease of use due to a single dose of 2 tablets of 20 mg once a day in a standard dose; good tolerability and favorable safety profile; proven bioequivalence to the reference drug. In light of the new Eurasian recommendations for the diagnosis and treatment of PH, tadalafil has a wide field for clinical use, which will improve the treatment options for patients with PAH both in mono- and combination therapy.

Right ventricular performance during acute hypoxic exercise.

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34±10 years, 7males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( )=0.21) and isobaric hypoxic ( =0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic and again at 50% hypoxic ( =0.12). Median (interquartile range) values for non-invasive values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P<0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P=0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax , and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% . During submaximal exercise at 50% of hypoxic , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an =0.12 and the associated increase in PA pressures. KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

Role of neutrophil myeloperoxidase in the development and progression of high-altitude pulmonary edema

BackgroundNeutrophil infiltration and hypoxic pulmonary vasoconstriction induced by hypobaric hypoxic stress are vital in high-altitude pulmonary edema (HAPE). Myeloperoxidase (MPO), an important enzyme in neutrophils, is associated with inflammation and oxidative stress and is also involved in the regulation of nitric oxide synthase (NOS), an enzyme that catalyzes the production of the vasodilatory factor nitric oxide (NO). However, the role of neutrophil MPO in HAPE's progression is still uncertain. Therefore, we hypothesize that MPO is involved in the development of HAPE via NOS. MethodsIn Xining, China (altitude: 2260 m), C57BL/6 N wild-type and mpo−/− mice served as normoxic controls, while a hypobaric chamber simulated 7000 m altitude for hypoxia. L-NAME, a nitric oxide synthase (NOS) inhibitor to inhibit NO production, was the experimental drug, and D-NAME, without NOS inhibitory effects, was the control. After measuring pulmonary artery pressure (PAP), samples were collected and analyzed for blood neutrophils, oxidative stress, inflammation, vasoactive substances, pulmonary alveolar-capillary barrier permeability, and lung tissue morphology. ResultsWild-type mice's lung injury scores, permeability, and neutrophil counts rose at 24 and 48 h of hypoxia exposure. Under hypoxia, PAP increased from 12.89 ± 1.51 mmHg under normoxia to 20.62 ± 3.33 mmHg significantly in wild-type mice and from 13.24 ± 0.79 mmHg to 16.50 ± 2.07 mmHg in mpo−/− mice. Consistent with PAP, inducible NOS activity, lung permeability, lung injury scores, oxidative stress response, and inflammation showed more significant increases in wild-type mice than in mpo−/− mice. Additionally, endothelial NOS activity and NO levels decreased more pronouncedly in wild-type mice than in mpo−/− mice. NOS inhibition during hypoxia led to more significant increases in PAP, permeability, and lung injury scores compared to the drug control group, especially in wild-type mice. ConclusionMPO knockout reduces oxidative stress and inflammation to preserve alveolar-capillary barrier permeability and limits the decline in endothelial NOS activity to reduce PAP elevation during hypoxia. MPO inhibition emerges as a prospective therapeutic strategy for HAPE, offering avenues for precise interventions.

Up-regulated expression of two-pore domain K+ channels, KCNK1 and KCNK2, is involved in the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe and rare disease in the cardiopulmonary system. Its pathogenesis involves vascular remodeling of the pulmonary artery, which results in progressive increases in pulmonary arterial pressure. Chronically increased pulmonary arterial pressure causes right ventricular hypertrophy and subsequent right heart failure. Pulmonary vascular remodeling is attributed to the excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), which are induced by enhanced Ca2+ signaling following the up-/down-regulation of ion channel expression. In the present study, the functional expression of two-pore domain potassium KCNK channels was investigated in PASMCs from idiopathic PAH (IPAH) patients and experimental pulmonary hypertensive (PH) animals. In IPAH-PASMCs, the expression of KCNK1/TWIK1 and KCNK2/TREK1 channels was up-regulated, whereas that of KCNK3/TASK1 and KCNK6/TWIK2 channels was down-regulated. The similar up-regulated expression of KCNK1 and KCNK2 channels was observed in the pulmonary arterial smooth muscles of monocrotaline-induced PH rats, Sugen 5416/hypoxia-induced PH rats, and hypoxia-induced PH mice. The facilitated proliferation of IPAH-PASMCs was suppressed by the KCNK channel blockers, quinine and tetrapentylammonium. The migration of IPAH-PASMCs was also suppressed by these channel blockers. Furthermore, increases in the proliferation and migration were inhibited by the siRNA knockdown of KCNK1 or KCNK2 channels. The siRNA knockdown also caused membrane depolarization and subsequent decrease in cytosolic [Ca2+]. The phosphorylated level of c-Jun N-terminal kinase (JNK) was elevated in IPAH-PASMCs compared to normal-PASMCs. The increased phosphorylation was significantly reduced by the siRNA knockdown of KCNK1 or KCNK2 channels. Collectively, these findings indicate that the up-regulated expression of KCNK1 and KCNK2 channels facilitates the proliferation and migration of PASMCs via enhanced Ca2+ signaling and JNK signaling pathway, which is associated with vascular remodeling in PAH.

Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report

BackgroundHemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment.Case presentationThis report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful.ConclusionNumerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here.

Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts.

Cauterization of the root of the left coronary artery (LCA) in the neonatal heart on postnatal day 1 (P1) resulted in large, reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The response of both chambers to LV myocardial infarction involved enhanced cardiomyocyte (CM) division and binucleation, as well as LV revascularization, leading to restored heart function within 7 days post surgery (7 dps). By contrast, infarction of P3 mice resulted in cardiac scarring without a significant regenerative and adaptive response of the LV and the RV, leading to subsequent heart failure and death within 7 dps. The prominent RV myocyte expansion in P1 mice involved an acute increase in pulmonary arterial pressure and a unique gene regulatory response, leading to an increase in RV mass and preserved heart function. Thus, distinct adaptive mechanisms in the RV, such as CM proliferation and RV expansion, enable marked cardiac regeneration of the infarcted LV at P1 and full functional recovery.

Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559m.

High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2 =12% for 2h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559m by Doppler echocardiography including global longitudinal strain (GLS). SPAP increase was higher in HAPH subjects (∆=10.2vs. ∆=32.0mm Hg, p<.001). LV eccentricity index (∆=.15vs. ∆=.31, p=.009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p=.00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50mm Hg. LV-EF (∆=4.5vs. ∆=6.7%, p=.24) increased in both groups. LV-GLS (∆=1.2vs. ∆=1.1 -%, p=.60) increased slightly. RV end-diastolic (∆=2.20vs. ∆=2.7cm2 , p=.36) and end-systolic area (∆=2.1vs. ∆=2.7cm2 , p=.39), as well as RA end-systolic area index (∆=-.9vs. ∆=.3cm2 /m2 , p=.01) increased, RV-FAC (∆=-2.9vs. ∆=-4.7%, p=.43) decreased, this was more pronounced in HAPH, RV-GLS (∆=1.6vs. ∆=-.7 -%, p=.17) showed marginal changes. LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study.

An increasing number of hypertensive persons travel to high altitude while using antihypertensive medications such as betablockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, β-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC). In seven healthy male lowlanders, pulmonary artery pressure was invasively measured without medication, with PROP and PROP+GLYC, both at sea level (SL, 488m) and after a three-week sojourn at 3454m altitude (HA). Bilateral thigh-cuff release maneuvers were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility. At SL, PROP increased Ppa and PVR from (mean±SEM) 14±1 to 17±1mmHg and from 69±8 to 108±11dyn*s*cm-5 (21 and 57% increase, p=0.01 and p<0.0001). The PVR response to PROP was amplified at HA to 76% (p<0.0001, p[interaction]=0.05). At both altitudes, PROP+GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9±0.5 to 1.7±0.2 at HA (p<0.0001) and to 1.2±0.2 with PROP, and further decreased to 0.9±0.2%*mmHg-1 with PROP+GLYC (p=0.01). Our data show that β-adrenergic blockade increases, and muscarinic blockade decreases PVR, whereas both increase pulmonary artery elastance. Future studies may confirm potential implications from the finding that β-adrenergic blockade exaggerates HPV for the management of mountaineers using β-blockers for prevention or treatment of cardiovascular conditions.

Invasive haemodynamics at rest and exercise in cardiac amyloidosis.

Our aim was to investigate haemodynamics at rest and during exercise in patients with transthyretin cardiomyopathy (ATTR-CM) in light of the 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines on pulmonary hypertension (PH). We performed right heart catheterization (RHC) in 57 subjects with ATTR-CM. The proportion of patients with PH was 77% according to the 2022 guidelines versus 47% when applying the 2015 guidelines. Isolated post-capillary PH and combined pre- and post-capillary PH were most prevalent. Thirty-six patients underwent a supine bicycle cardiopulmonary exercise test during RHC. Exercise-induced PH was defined as an increase in mean pulmonary arterial pressure from rest to exercise per increase in cardiac output (ΔmPAP/ΔCO) of > 3mmHg/L/min. An increase in pulmonary arterial wedge pressure per change in cardiac output (ΔPAWP/ΔCO) from rest to exercise >2mmHg/L/min was considered suggestive of post-capillary exercise-induced PH. All but two patients who exercised during RHC developed exercise-induced PH. The median ΔmPAP/ΔCO was 7.2mmHg/L/min and ΔPAWP/ΔCO was 5.1mmHg/L/min. The median ΔRAP/ΔCO was 3.6mmHg/L/min and ΔRAP/ΔPAWP was 0.6mmHg/L/min. Most patients with ATTR-CM have isolated post-capillary or combined pre- and post-capillary PH at rest, and almost all patients develop exercise-induced PH with a large post-capillary component. There was a pronounced, but balanced increase in atrial pressures on exercise.

The FXYD1 protein plays a protective role against pulmonary hypertension and arterial remodeling via redox and inflammatory mechanisms.

Pulmonary hypertension (PH) consists of a heterogenous group of diseases that culminate in increased pulmonary arterial pressure and right ventricular (RV) dysfunction. We sought to investigate the role of FXYD1, a small membrane protein that modulates Na+-K+-ATPase function, in the pathophysiology of PH. We mined online transcriptome databases to assess FXYD1 expression in PH. We characterized the effects of FXYD1 knockout (KO) in mice on right and left ventricular (RV and LV) function using echocardiography and measured invasive hemodynamic measurements under normal conditions and after treatment with bleomycin sulfate or chronic hypoxia to induce PH. Using immunohistochemistry, immunoblotting, and functional assays, we examined the effects of FXYD1 KO on pulmonary microvasculature and RV and LV structure and assessed signaling via endothelial nitric oxide synthase (eNOS) and inflammatory pathways. FXYD1 lung expression tended to be lower in samples from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with controls, supporting a potential pathophysiological role. FXYD1 KO mice displayed characteristics of PH including significant increases in pulmonary arterial pressure, increased muscularization of small pulmonary arterioles, and impaired RV systolic function, in addition to LV systolic dysfunction. However, when PH was stimulated with standard models of lung injury-induced PH, there was no exacerbation of disease in FXYD1 KO mice. Both the lungs and left ventricles exhibited elevated nitrosative stress and inflammatory milieu. The absence of FXYD1 in mice results in LV inflammation and cardiopulmonary redox signaling changes that predispose to pathophysiological features of PH, suggesting FXYD1 may be protective.NEW & NOTEWORTHY This is the first study to show that deficiency of the FXYD1 protein is associated with pulmonary hypertension. FXYD1 expression is lower in the lungs of people with idiopathic pulmonary artery hypertension. FXYD1 deficiency results in both left and right ventricular functional impairment. Finally, FXYD1 may endogenously protect the heart from oxidative and inflammatory injury.

Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

Abstract Background: The main objective measure to assess the health of the Fontan circulation is the pressure measurement of the superior vena cava or pulmonary arteries. We reviewed the literature for benefits of measuring resting pressure in the Fontan circuit and explored whether dynamic measurement by volume loading or exercise has the potential to refine this diagnostic tool. Methods: PubMed was searched for articles showing a relationship between resting post-operative central venous pressure or pulmonary artery pressure and Fontan failure. Relationships between post-operative central venous pressure or pulmonary artery pressure and volume loading changes, such as during exercise or volume loading during cardiac catheterization, were also queried. Results: A total of 44 articles mentioned relationships between resting central venous pressure or pulmonary artery pressure and Fontan failure. Only 26 included an analysis between the variables and only seven of those articles found pressure to be predictive of Fontan failure. Ten articles examined the relationship between exercise or volume loading and outcomes and demonstrated a large individual variation of pressures under these dynamic conditions. Conclusions: Based on current literature, there is not a lot of strong evidence to show that elevated resting central venous pressure or pulmonary artery pressure is predictive of Fontan failure. Some individuals experience dramatic increases in central venous pressure or pulmonary artery pressure under increased loading conditions with exercise or bolus fluid infusion, while others experience increases closer to that of a healthy control population. Further studies are needed to examine whether more dynamic and continuous monitoring of systemic venous pressures might better predict outcomes in patients with Fontan circulation.