scholarly journals Endothelin in the perinatal circulation

2003 ◽  
Vol 81 (6) ◽  
pp. 644-653 ◽  
Author(s):  
Thérèse Perreault ◽  
Flavio Coceani
Keyword(s):  
Pulmonary Hypertension ◽  
Transition Period ◽  
Morphological Changes ◽  
Ductus Arteriosus ◽  
Negative Inotropic Effect ◽  
Pulmonary Vasculature ◽  
Practical Applications ◽  
Neonatal Cardiomyocytes ◽  
Nitric Oxide Formation ◽  
Pulmonary Vasoconstriction

During the fetal period, blood is oxygenated through the placenta, and most of the cardiac output bypasses the lung through the ductus arteriosus. At birth, pulmonary vascular resistance falls with the initiation of ventilation. Coincidentally, the ductus arteriosus constricts. Endothelin-1 (ET-1) appears to play an important role during that transition period and postnatally. ET-1 can dramatically increase resistance in the placental microcirculation and may be involved in blood flow redistribution with hypoxia. At birth, the increase in oxygen tension is important in triggering ductus vasoconstriction. It is proposed that oxygen triggers closure of the ductus arteriosus by activating a specific, cytochrome P450-linked reaction, which in turn stimulates the synthesis of ET-1. On the neonatal heart, ET-1 has a positive chronotropic but negative inotropic effect. In the newborn piglet and the fetal lamb, both term and preterm, ET-1 causes a potent, long-lasting pulmonary vasoconstriction. Furthermore, a transient dilator response has been identified, and it is ascribed to nitric oxide formation. ET receptors are abundant in the piglet pulmonary vasculature. They are predominantly of the ETA constrictor subtype, though ETB2 constrictor receptors may also be present in certain species. The dilator response is linked to the ETB1 receptor, and the number of ETB1 receptors is reduced in hypoxia-induced pulmonary hypertension. ET-1 appears to be a causative agent in the pathogenesis of hypoxia- and hyperoxia-induced pulmonary hypertension as demonstrated by reversal of hemodynamic and morphological changes with treatment with an ETA receptor antagonist. Findings are amenable to practical applications in the management of infants with pulmonary hypertension or requiring persistent patency of the ductus arteriosus.Key words: ductus arteriosus, neonatal pulmonary circulation, neonatal pulmonary hypertension, neonatal cardiomyocytes, fetus.

scholarly journals Pulmonary Hypertension with Prolonged Patency of the Ductus Arteriosus in Preterm Infants

Children ◽  
2020 ◽  
Vol 7 (9) ◽  
pp. 139
Author(s):  
Ranjit Philip ◽  
Vineet Lamba ◽  
Ajay Talati ◽  
Shyam Sathanandam
Keyword(s):  
Decision Making ◽  
Pulmonary Hypertension ◽  
Preterm Infants ◽  
Premature Infants ◽  
Ductus Arteriosus ◽  
Pulmonary Vasculature ◽  
Short Term ◽  
Diagnostic Cardiac Catheterization ◽  
Patent Ductus

There continues to be a reluctance to close the patent ductus arteriosus (PDA) in premature infants. The debate on whether the short-term outcomes translate to a difference in long-term benefits remains. This article intends to review the pulmonary vasculature changes that can occur with a chronic hemodynamically significant PDA in a preterm infant. It also explains the rationale and decision-making involved in a diagnostic cardiac catheterization and transcatheter PDA closure in these preterm infants.

Pulmonary hypertension in dogs: an overview

2021 ◽  
Vol 26 (4) ◽  
pp. 1-9
Author(s):  
Elizabeth Bode ◽  
Zuzanna Uljanowska
Keyword(s):  
Pulmonary Hypertension ◽  
Septal Defect ◽  
Ductus Arteriosus ◽  
Pulmonary Vasculature ◽  
Diagnostic Process ◽  
Advanced Imaging ◽  
Severe Respiratory Distress ◽  
Definition Of ◽  
Patent Ductus

Pulmonary hypertension is a complex syndrome that can be caused by congenital or acquired disease. Congenital conditions include cardiac shunts, such as ventricular septal defect and patent ductus arteriosus. Acquired diseases that eventually lead to pulmonary hypertension include cardiac, systemic and pulmonary pathologies, for example late stage myxomatous mitral valve disease and interstitial lung disease such as idiopathic pulmonary fibrosis. It can be a challenge to identify pulmonary hypertension because the diagnostic process usually requires advanced imaging tools, such as echocardiography, and a good understanding of the animal's history. Pulmonary hypertension can have a profound effect on a dog's quality of life and can lead to severe respiratory distress and damage to the cardiovascular system. Therefore pulmonary hypertension needs to be identified and addressed promptly. Pulmonary hypertension can be reversible in the early stages, but it is generally not reversible when chronic changes to the pulmonary vasculature have occurred. The article reviews the definition of pulmonary hypertension and its pathophysiology, its diagnosis and treatment in canine patients, and discusses the most common congenital and acquired causes.

Platelet Factor 4 Injection Produces Acute Pulmonary Hypertension in the Awake Lamb 

1995 ◽  
Vol 82 (1) ◽  
pp. 183-187 ◽  
Author(s):  
Matt M. Kurrek ◽  
Marianne Winkler ◽  
Dwight R. Robinson ◽  
Warren M. Zapol
Keyword(s):  
Pulmonary Hypertension ◽  
Intravenous Administration ◽  
Platelet Factor 4 ◽  
Thromboxane B2 ◽  
Pulmonary Vasculature ◽  
Intravenous Bolus ◽  
Platelet Factor ◽  
Pulmonary Vasoconstriction ◽  
Heparin Anticoagulation ◽  
Protamine 2

Background Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morphologic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs. Methods The authors evaluated the hemodynamic response and plasma release rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically monitored lambs. Each lamb underwent up to three random challenges with a 2-h recovery period between each challenge. Results In two lambs, systemic anticoagulation with heparin followed by reversal of anticoagulation with an intravenous bolus of rPF4 (4 mg/kg) led to acute pulmonary vasoconstriction and hypertension with the release of thromboxane (peak pulmonary artery pressure [Ppa] 40 and 33 mmHg and peak plasma thromboxane B2 50 and 30 ng/ml, respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B2 from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction lasted approximately 5 min and was completely prevented by pre-treatment with oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) followed by protamine (2 mg/kg) consistently produced acute pulmonary vasoconstriction and hypertension. Conclusions Intravenous injection of human rPF4 into the awake lamb produces acute pulmonary vasoconstriction and hypertension associated with thromboxane release into circulating blood. The effects of rPF4 on the pulmonary vasculature should be evaluated in primates before rPF4 is substituted for protamine in reversing heparin anticoagulation in humans.

Pulmonary arterial smooth muscle contractility in hypoxia-induced pulmonary hypertension

1994 ◽  
Vol 77 (1) ◽  
pp. 406-414 ◽  
Author(s):  
S. L. Griffith ◽  
R. A. Rhoades ◽  
C. S. Packer
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Chronic Hypoxia ◽  
Morphological Changes ◽  
Pulmonary Vasculature ◽  
Sprague Dawley ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Cross Sectional ◽  
Pulmonary Arterial

The highly compliant low-resistance pulmonary vasculature is markedly altered with chronic hypoxia. Remodeling in response to hypoxia and/or hypertension involves hypertrophy and hyperplasia of smooth muscle and excessive deposition of connective tissue that likely contributes to the maintenance or exasperates the already elevated pulmonary arterial (PA) pressure. The purpose of this study was to investigate the effect of chronic hypoxia on the contractile properties of PA smooth muscle. Isometric and isotonic experiments were performed on excised PA rings from pulmonary hypertensive (induced by 14 days of hypoxia) Sprague-Dawley rats. A doubling of the vessel wall thickness occurred during the development of hypoxia-induced pulmonary hypertension. Functionally, there was a decrease in isometric stress (force to cross-sectional area ratio). No difference was detected in the velocity of shortening or in total shortening ability. This study provides evidence that, in addition to the morphological changes, changes in PA smooth muscle contractility also appear to play a role in the development and/or maintenance of hypoxia-induced pulmonary hypertension.

Reduced vasodilator response to ANF in hypoxia-induced pulmonary hypertension in the newborn piglet

1997 ◽  
Vol 273 (2) ◽  
pp. L289-L295 ◽  
Author(s):  
T. Perreault ◽  
J. Baribeau ◽  
R. Gosselin ◽  
J. Gutkowska
Keyword(s):  
Pulmonary Hypertension ◽  
Natriuretic Peptide ◽  
Vascular Reactivity ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
Binding Characteristics ◽  
Pulmonary Vasoconstriction ◽  
Clearance Receptor ◽  
Circulating Levels ◽  
Specific Ligand

Recent evidence suggests that, in adult animals with hypoxia-induced pulmonary hypertension, atrial natriuretic factor (ANF) may modulate pulmonary vascular tone and may have a protective effect. However, its role in the pathogenesis of pulmonary hypertension of the newborn is unknown. We hypothesized that, in the newborn, hypoxia-induced pulmonary hypertension would result in ANF receptor downregulation, resulting in decreased dilator response, favoring pulmonary vasoconstriction and vascular remodeling. Therefore, we studied, in 1-day-old piglets exposed to hypoxia (fraction of inspired O2 0.10) for 3 or 14 days to induce pulmonary hypertension, 1) ANF release by measuring circulating levels of ANF by radioimmunoassay in pulmonary artery and veins, 2) pulmonary vascular reactivity to ANF using isolated perfused lungs, and 3) binding characteristics by examining the concentration dependence of ANF binding and competitive binding of 125I-labeled ANF with ANF, brain natriuretic peptide, C-type natriuretic peptide, and the specific ligand for ANF clearance receptor on microsomes from pulmonary arteries (down to 100 microns). ANF circulating levels are increased after exposure to hypoxia compared with normoxia, reaching significance at 14 days (P < 0.005). The magnitude of ANF dilator response is diminished after exposure to hypoxia (P < 0.05). Saturation studies reveal that the number of ANF receptors is diminished in hypoxia after 3 days but reaches significance after 14 days (P < 0.01) compared with their respective normoxic control. At either condition, the majority of these receptors are of the functional type, whereas clearance receptors are virtually undectable. These results suggest that hypoxia increases circulating ANF and causes a decreased responsiveness of the pulmonary vasculature to ANF. Receptor down-regulation may explain part of the reduced dilator response, although the involvement of other mechanisms is not excluded.

Hypoxic Pulmonary Vasoconstriction and Chronic Lung Disease

2013 ◽  
Vol 12 (3) ◽  
pp. 135-144 ◽  
Author(s):  
Erik R. Swenson
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Disease ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
World Health ◽  
Disease States ◽  
Pulmonary Vasoconstriction ◽  
Local Ventilation ◽  
Pulmonary Vascular Endothelium ◽  
Health And Disease ◽  
Health Organization

Hypoxic vasoconstriction in the lung is a unique and fundamental characteristic of the pulmonary circulation. It functions in health and disease states to better preserve ventilation-perfusion matching by diverting blood flow to better ventilated regions when local ventilation is compromised. As more areas of lung become hypoxic either with high altitude or global lung disease, then hypoxic pulmonary vasoconstriction (HPV) becomes less effective in ventilation-perfusion matching and can lead to pulmonary hypertension. HPV is intrinsic to the vascular smooth muscle and its mechanisms remain poorly understood. In addition, the pulmonary vascular endothelium, red cells, lung innervation, and numerous circulating vasoactive agents also affect the strength of HPV. This review will discuss the pathophysiology of HPV and address its role in pulmonary hypertension associated with World Health Organization Group 3 diseases. When sustained beyond many hours, HPV may initiate pulmonary vascular remodeling and lead to more fixed and less oxygen-responsive pulmonary hypertension if the hypoxic stimulus is maintained.

scholarly journals Randomized Trial of Oxygen Saturation Targets during and after Resuscitation and Reversal of Ductal Flow in an Ovine Model of Meconium Aspiration and Pulmonary Hypertension

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 594
Author(s):  
Amy L. Lesneski ◽  
Payam Vali ◽  
Morgan E. Hardie ◽  
Satyan Lakshminrusimha ◽  
Deepika Sankaran
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Oxygen Saturation ◽  
Ductus Arteriosus ◽  
Neonatal Resuscitation ◽  
Meconium Aspiration Syndrome ◽  
Ovine Model ◽  
Neurodevelopmental Outcomes ◽  
Meconium Aspiration ◽  
Blood Flows

Neonatal resuscitation (NRP) guidelines suggest targeting 85–95% preductal SpO2 by 10 min after birth. Optimal oxygen saturation (SpO2) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (QPA), carotid (QCA)and ductal (QDA) blood flows between standard (85–94%) and high (95–99%) SpO2 targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85–94%) or high (95–99%) SpO2 targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO2 targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO2 target (7.4 (4.4–10.8) min) compared to standard SpO2 target (31.5 (21–66.2) min, p = 0.03). QPA was significantly higher during the first 10 min after birth with higher SpO2 target. At 60 min after birth, the QPA, QCA and QDA were not different between the groups. To conclude, targeting SpO2 of 95–99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase QPA but no differences were observed at 60 min. Clinical studies comparing low and high SpO2 targets assessing hemodynamics and neurodevelopmental outcomes are warranted.

scholarly journals The mechanism of ions in pulmonary hypertension

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402098794
Author(s):  
Guogu Liu ◽  
Daiyan Fu ◽  
Heshen Tian ◽  
Aiguo Dai
Keyword(s):  
Pulmonary Hypertension ◽  
Calcium Ion ◽  
Pulmonary Arteries ◽  
Chloride Ion ◽  
Vasoactive Substances ◽  
Pulmonary Vasoconstriction ◽  
Concentration Of Ions ◽  
Inducing Factors ◽  
Effective Drugs ◽  
Pathological Manifestation

Pulmonary hypertension（PH）is a kind of hemodynamic and pathophysiological state, in which the pulmonary artery pressure (PAP) rises above a certain threshold. The main pathological manifestation is pulmonary vasoconstriction and remodelling progressively. More and more studies have found that ions play a major role in the pathogenesis of PH. Many vasoactive substances, inflammatory mediators, transcription-inducing factors, apoptosis mediators, redox substances and translation modifiers can control the concentration of ions inside and outside the cell by regulating the activity of ion channels, which can regulate vascular contraction, cell proliferation, migration, apoptosis, inflammation and other functions. We all know that there are no effective drugs to treat PH. Ions are involved in the occurrence and development of PH, so it is necessary to clarify the mechanism of ions in PH as a therapeutic target for PH. The main ions involved in PH are calcium ion (Ca2+), potassium ion (K+), sodium ion (Na+) and chloride ion (Cl–). Here, we mainly discuss the distribution of these ions and their channels in pulmonary arteries and their role in the pathogenesis of PH.

scholarly journals Neonatal and Postneonatal Pulmonary Hypertension

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 131
Author(s):  
Satyan Lakshminrusimha
Keyword(s):  
Pulmonary Hypertension ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Right Ventricular Dysfunction ◽  
Fold Increase ◽  
Pulmonary Vein Stenosis ◽  
Term Infants ◽  
Pulmonary Vasodilators ◽  
Non Invasive Ventilation ◽  
Early Closure

During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure.

Sign in / Sign up

Export Citation Format

Share Document