It’s Time to Put the Term “Pulmonary Vasodilators” to Rest

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.

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Inhaled Selective Pulmonary Vasodilators for Adult Lung Transplantation

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2021.01.1925 ◽

2021 ◽

Vol 40 (4) ◽

pp. S75-S76

Author(s):

K. Ghadimi ◽

J. Cappiello ◽

M. Cooter ◽

J. Haney ◽

J. Reynolds ◽

...

Keyword(s):

Lung Transplantation ◽

Adult Lung ◽

Pulmonary Vasodilators

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Effect of Coronavirus Disease 2019 in Pulmonary Circulation. The Particular Scenario of Precapillary Pulmonary Hypertension

Diagnostics ◽

10.3390/diagnostics10080548 ◽

2020 ◽

Vol 10 (8) ◽

pp. 548 ◽

Cited By ~ 2

Author(s):

Jorge Nuche ◽

Teresa Segura de la Cal ◽

Carmen Jiménez López Guarch ◽

Francisco López-Medrano ◽

Carmen Pérez-Olivares Delgado ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Respiratory Infections ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

The Elderly ◽

Angiotensin Converting Enzyme 2 ◽

Common Features ◽

Pulmonary Vasodilators ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial ◽

Low Incidence

The Coronavirus Disease of 2019 (COVID-19) has supposed a global health emergency affecting millions of people, with particular severity in the elderly and patients with previous comorbidities, especially those with cardiovascular disease. Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) could represent an especially vulnerable population because of the high mortality rates reported for respiratory infections. However, the number of COVID-19 cases reported among PAH and CTEPH patients is surprisingly low. Furthermore, the clinical picture that has been described in these patients is far from the severity that experts would expect. Endothelial dysfunction is a common feature between patients with PAH/CTEPH and COVID-19, leading to ventilation/perfusion mismatch, vasoconstriction, thrombosis and inflammation. In this picture, the angiotensin-converting enzyme 2 plays an essential role, being directly involved in the pathophysiology of both clinical entities. Some of these common characteristics could explain the good adaptation of PAH and CTEPH patients to COVID-19, who could also have obtained a benefit from the disease’s specific treatments (anticoagulant and pulmonary vasodilators), probably due to its protective effect on the endothelium. Additionally, these common features could also lead to PAH/CTEPH as a potential sequelae of COVID-19. Throughout this comprehensive review, we describe the similarities and differences between both conditions and the possible pathophysiological and therapeutic-based mechanisms leading to the low incidence and severity of COVID-19 reported in PAH/CTEPH patients to date. Nevertheless, international registries should look carefully into this population for better understanding and management.

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Newborn rat response to single vs. combined cGMP-dependent pulmonary vasodilators

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00164.2013 ◽

2014 ◽

Vol 306 (2) ◽

pp. L207-L215 ◽

Cited By ~ 9

Author(s):

Masahiro Enomoto ◽

Amish Jain ◽

Jingyi Pan ◽

Yulia Shifrin ◽

Todd Van Vliet ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Synergistic Effect ◽

Soluble Guanylate Cyclase ◽

Pulmonary Arteries ◽

Small Heat Shock Protein ◽

No Donor ◽

Clinical Exposure ◽

Pulmonary Vasodilators ◽

Pulmonary Vasodilator

Inhaled nitric oxide (NO) and other cGMP- or cAMP-dependent pulmonary vasodilators are often used in combination for the treatment of the persistent pulmonary hypertension of the newborn syndrome. There is in vitro evidence to indicate that NO downregulate the pulmonary vascular response to cGMP-dependent agonists raising concern as to whether a synergistic effect is observed when employing a combined strategy in newborns. Hypothesizing that a synergistic effect is absent, we evaluated newborn and juvenile rat pulmonary arteries to determine the individual and combined vasodilatory effect of cGMP- and cAMP-dependent agonists. In precontracted near-resistance pulmonary arteries, the addition of sildenafil reduced vasorelaxation response to NO donor S-nitroso- N-acetyl penicillamine (SNAP). A similar decrease in SNAP-induced vasodilation was observed in arteries pretreated with BAY 41–2272 (10−9 M), a soluble guanylate cyclase stimulator cGMP, and its downstream protein kinase activator. cGMP also reduced the vasorelaxant response to the cAMP-dependent forskolin. Inhibition of endogenous vascular NO generation enhanced SNAP-induced relaxation. The present data suggest that the mechanism involved in the cGMP desensitization to other relaxant agonists involves downregulation of the small heat shock protein HSP20 and is evident in rat pulmonary and systemic vascular smooth muscle cells. In newborn rats with chronic hypoxia-induced pulmonary hypertension, the combination of sildenafil and inhaled NO resulted in a lesser reduction in pulmonary vascular resistance compared with their individual effect. These data suggest that clinical exposure to one cGMP-dependent pulmonary vasodilator may affect the response to other cGMP- or cAMP-mediated agonists.

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Comparison of outcomes of infants with giant omphaloceles over two decades

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-200451 ◽

2020 ◽

pp. 1-5

Author(s):

R.E. Witt ◽

M. Singhal ◽

A.J. Vachharajani

Keyword(s):

Mechanical Ventilation ◽

Medical Records ◽

Invasive Mechanical Ventilation ◽

Informed Decision Making ◽

Membrane Oxygenator ◽

Associated Anomalies ◽

Single Institution ◽

Extracorporeal Membrane Oxygenator ◽

Pulmonary Vasodilators ◽

Improved Outcomes

BACKGROUND: The purpose of this study was to compare the outcomes of infants with giant omphalocele (GO) born in two different epochs over two decades at a single institution. Specifically, it examined whether the utilization of selective pulmonary vasodilators and extracorporeal membrane oxygenator (ECMO) in the management of pulmonary hypertension in the second epoch were associated with improved outcomes. METHODS: The medical records of all patients diagnosed with GO at a large children’s hospital from January 1, 1996 to December 31, 2016 were reviewed and divided into two epochs. Patients were classified as having an isolated GO or GO with minor or major associated anomalies. GO was defined as a defect more than or equal to 5 cm in size and/or liver in the sac. RESULTS: During the study period, 59 infants with GO were identified. The duration of invasive mechanical ventilation was significantly shorter among the survivors from the second epoch (p = 0.03), with none greater than seven days. There were no significant differences in the outcomes of survival to NICU discharge and length of stay (LOS) between infants in the two epochs. CONCLUSIONS: Infants with GO who required invasive mechanical ventilation for more than seven days did not survive in the second epoch. Survival did not improve with uses of selective pulmonary vasodilators and ECMO. This information could be shared with families during prenatal and postnatal counselling to facilitate informed decision making regarding goals of care.

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A systematic review of the evidence supporting post-operative medication use in congenital heart disease

Cardiology in the Young ◽

10.1017/s1047951121001463 ◽

2021 ◽

pp. 1-27

Author(s):

Elizabeth J. Thompson ◽

Henry P. Foote ◽

Caitlin E. King ◽

Sabarish Srinivasan ◽

Elizabeth C. Ciociola ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Adverse Events ◽

Drug Development ◽

Drug Disposition ◽

Controlled Vocabulary ◽

Coagulation System ◽

Future Research ◽

Pulmonary Vasodilators ◽

Post Operative Period ◽

Operative Care

Abstract Background: Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass. Methods: We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass. Results: We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety. Conclusion: In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.

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VENTILATORY SUPPORT IN SARS-VOC-2 DURING INTENSIVE THERAPY

10.1101/2020.05.14.20098608 ◽

2020 ◽

Author(s):

Javier Eliecer Pereira Rodriguez ◽

Juan Camilo Quintero Gomez ◽

Otilio Lopez Florez ◽

Sandra Sharon Waiss Skvirsky ◽

Ximena Velasquez Badillo

Keyword(s):

Mechanical Ventilation ◽

Observational Studies ◽

Intensive Therapy ◽

Ventilatory Support ◽

Cochrane Collaboration ◽

Plateau Pressure ◽

Lung Compliance ◽

Respiratory Support ◽

Pulmonary Vasodilators ◽

Critical Patients

Introduction: The SARS-CoV-2 disease outbreak has now become a pandemic. Critical patients with COVID-19 require basic and advanced respiratory support. Therefore, the objective was to describe the ventilatory support strategies in SARS-CoV-2 during intensive therapy. Materials and methods: A systematic review of observational studies of the available scientific literature was performed in accordance with the recommendations of the Cochrane collaboration and the criteria of the PRISMA Declaration. Results: Fifteen observational studies were included that gave a study population of 4,081 patients. Mechanical ventilation is the main respiratory support treatment for critically ill patients, which should be administered as soon as normal oxygenation cannot be maintained, and despite the fact that there is no current consensus on the parameters of mechanical ventilation, the evidence collected suggests the use of Fio2 on average 50%, PEEP of 14 cmH2O, lung compliance of 29-37 ml per cm of water, driving pressure between 12-14 cm of water and a plateau pressure of 22-25 cm of water. Conclusions: IL-6 is shown as a possible marker of respiratory failure and a worse prognosis as well as obesity. In addition, the use of prone position, neuromuscular blockade, pulmonary vasodilators, ECMO, and mechanical ventilation based on the clinical conditions and needs of the patient with COVID-19 are strategies that could benefit patients entering intensive therapy for SARS-CoV- 2.

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Pulmonary Vasodilators—Treating the Right Ventricle

Anesthesiology Clinics ◽

10.1016/j.anclin.2008.01.010 ◽

2008 ◽

Vol 26 (2) ◽

pp. 337-353 ◽

Cited By ~ 16

Author(s):

John Granton ◽

Jakov Moric

Keyword(s):

Right Ventricle ◽

Pulmonary Vasodilators ◽

The Right

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Role of Inotropes, Pulmonary Vasodilators, and Other Pharmacologic Interventions for Right Ventricular Dysfunction

Mechanical Circulatory Support in End-Stage Heart Failure ◽

10.1007/978-3-319-43383-7_21 ◽

2017 ◽

pp. 227-233

Author(s):

Diyar Saeed

Keyword(s):

Right Ventricular ◽

Ventricular Dysfunction ◽

Right Ventricular Dysfunction ◽

Pulmonary Vasodilators

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Pulmonary Vasodilator Therapy in Children with Single Ventricle Physiology: Effects on Saturation and Pulmonary Arterial Pressure

Pediatric Cardiology ◽

10.1007/s00246-020-02424-w ◽

2020 ◽

Vol 41 (8) ◽

pp. 1651-1659

Author(s):

Ida Jeremiasen ◽

Karin Tran-Lundmark ◽

Nikmah Idris ◽

Phan-Kiet Tran ◽

Shahin Moledina

Keyword(s):

Arterial Pressure ◽

Single Ventricle ◽

Pulmonary Arterial Pressure ◽

Vasodilator Therapy ◽

Single Ventricle Physiology ◽

Pulmonary Vasodilators ◽

Mean Pulmonary Arterial Pressure ◽

Pulmonary Vasodilator ◽

Pulmonary Arterial ◽

Stage 1

AbstractIn children with single ventricle physiology, increased pulmonary vascular resistance may impede surgical progression or result in failing single ventricle physiology. The use of pulmonary vasodilators has been suggested as a potential therapy. However, knowledge on indication, dosage, and effect is limited. A retrospective case notes review of all (n = 36) children with single ventricle physiology, treated with pulmonary vasodilators by the UK Pulmonary Hypertension Service for Children 2004–2017. Therapy was initiated in Stage 1 (n = 12), Glenn (n = 8), or TCPC (n = 16). Treatment indications were high mean pulmonary arterial pressure, cyanosis, reduced exercise tolerance, protein-losing enteropathy, ascites, or plastic bronchitis. Average dose of sildenafil was 2.0 mg/kg/day and bosentan was 3.3 mg/kg/day. 56% had combination therapy. Therapy was associated with a reduction of the mean pulmonary arterial pressure from 19 to 14 mmHg (n = 17, p < 0.01). Initial therapy with one or two vasodilators was associated with an increase in the mean saturation from 80 to 85%, (n = 16, p < 0.01). Adding a second vasodilator did not give significant additional effect. 5 of 12 patients progressed from Stage 1 to Glenn, Kawashima, or TCPC, and 2 of 8 from Glenn to TCPC during a mean follow-up time of 4.7 years (0–12.8). Bosentan was discontinued in 57% and sildenafil in 14% of treated patients and saturations remained stable. Pulmonary vasodilator therapy was well tolerated and associated with improvements in saturation and mean pulmonary arterial pressure in children with single ventricle physiology. It appears safe to discontinue when no clear benefit is observed.

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