Chest
Original Research: PULMONARY HYPERTENSIONEtiology-Specific Endothelin-1 Clearance in Human Precapillary Pulmonary Hypertension
Section snippets
Study Subjects
Forty-five consecutive patients with precapillary PH (19 patients with idiopathic PAH [IPAH]16; 15 patients with PAH related to connective tissue disease [CTD]; 11 patients with CTEPH) and meeting the following criteria were studied. During ET-1 sampling, all patients were undergoing routine hemodynamic study as part of their evaluation or prior to initiation of therapy. IPAH was diagnosed when the patients fulfilled the criteria as established by the consensus group of the third World
Patient Characteristics
There were no significant differences between the disease groups with regard to age; heart rate; mean systemic, right atrial, pulmonary arterial, and wedge pressures; cardiac output; or systemic and pulmonary vascular resistances, with marked abnormalities in the hemodynamic characteristics being seen in all groups (Table 1). There was a very good (r = 0.89, p < 0.01) correlation between the thermodilution-derived plasma flow and the indicator dilution-derived plasma flow. However, the
Discussion
ET-1 may play a detrimental role in human PH.2, 22 ET receptor blockade improves hemodynamics, functional capacity, and survival in PAH patients.4, 5, 6, 23However, there is still incomplete understanding of ET homeostasis in the human pulmonary hypertensive lung. While excess pulmonary ET-1 synthesis contributes to the abnormally high levels,11 the importance of altered ET-1 extraction has not been studied. Furthermore, the importance of changes in ET receptor density and availability for
ACKNOWLEDGMENT
We are grateful to Alexandre Caron, Alan Moskovic, Nathalie Ruel, and Joseph Khoury for expert technical assistance. Drs. Robert Schlesinger, Leonidas Dragatakis, and Mark J. Eisenberg were of great assistance with cardiac catheterizations. We thank the nurses and technicians of the Jewish General Hospital Cardiac Catheterization Laboratory, and the Coronary Care Unit, for their generous and patient assistance.
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Cited by (49)
Lung Capillary Stress Failure and Arteriolar Remodelling in Pulmonary Hypertension Associated with Left Heart Disease (Group 2 PH)
2016, Progress in Cardiovascular DiseasesCitation Excerpt :Pulmonary vascular endothelial cells control tone through numerous pathways and molecules like nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostacyclin (PGI2), endothelin-1 (ET-1) as well as many additional factors including platelet-derived growth factor (PDGF), vascular endothelium growth factor (VEGF), vasoactive intestitinal peptide (VIP), urotensin, adrenomedullin and leukotrienes. In addition, the pulmonary vascular endothelium is an important site for metabolism and clearance of circulating mediators such as angiotensin-I, endothelin, serotonin, adrenomedullin, and many others through specific receptors, enzymes and transporters.11–17 The pulmonary endothelium will therefore modulate local, but also systemic vascular biology.
The effect of deep hypothermia on the human pulmonary circulation
2014, Journal of Thermal BiologyCitation Excerpt :These are associated with the NO–cGMP and PGI2–cAMP pathways as demonstrated in animal models of systemic arteries (Han et al., 2010). We used Endothelin-1 as this has been associated with the development of pulmonary hypertension (Langleben et al., 2006). The concentrations of Endothelin-1 were used as these have been shown by our group in the past to be the most effective in human pulmonary arteries (Bennett et al., 2004).
Biventricular structural and functional responses to aortic constriction in a rabbit model of chronic right ventricular pressure overload
2012, Journal of Thoracic and Cardiovascular SurgeryThe role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension
2011, Pharmacological ResearchCitation Excerpt :In these studies the overall picture is that ETA antagonism causes vasodilation, ETB antagonism causes vasoconstriction and that blocking ETB in conjunction with ETA blockade attenuates some of the vasodilatory effect of ETA blockade alone [95–97]. Although studies like these have not been performed in patients with PAH, it is likely that the ETB receptor is functional and that the raised levels of ET-1 seen in the human are from increased production rather than reduced clearance [98]. Furthermore, the selectivity of the ET receptor antagonist affects circulating levels of ET-1.
Endothelin-1 response to glucose and insulin among African Americans
2010, Journal of the American Society of HypertensionCitation Excerpt :Mechanisms for clearance of ET-1 in humans are controversial. Local clearance appears to be mediated by ET-B receptors.23–25 Previous studies indicate whole-body clearance of ET-1 via kidney, liver, and lung.26,27
This work was funded by operating grants (MOP-42476 and 67145 to DL, MOP-12887 to JD, MOP-68966 to JLS) from the Canadian Institutes of Health Research, and by the Bank of Montreal Center for the Study of Heart Disease in Women at the Jewish General Hospital.
Dr. Langleben is a Chercheur-Boursier Clinicien National (National Clinical Research Scholar), and Dr. Dupuis is a Chercheur-Boursier Clinicien Senior (Senior Clinical Research Scholar), of the Fonds de la Recherche en Sante du Quebec. Dr. Senécal, M. Giovinazzo, and I. Langleben have no conflicts of interest to declare. Drs. D. Langleben, Dupuis, Hirsch, and Baron have served as speakers, investigators and/or consultants for one or more of Actelion Inc., Encysive Corporation, and Myogen Inc.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).