Pulmonary microvascular lesions regress in reperfused chronic thromboembolic pulmonary hypertension

Autor: Elie Fadel, Julien Guihaire, Lilia Lamrani, Peter Dorfmüller, Saadia Eddahibi, David Boulate, Philippe Dartevelle, Olaf Mercier, Marc Humbert, Jennifer Arthur-Ataam, Benoit Decante, Frédéric Perros
Přispěvatelé: Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie et Réanimation Respiratoire (DHU TORINO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre-Centre de Référence de l'Hypertension Pulmonaire Sévère, Labex LERMIT,Hypertension Artérielle Pulmonaire, Service de Chirurgie Thoracique,Vasculaire et deTransplantationCardiopulmonaire, Centre chirurgical Marie Lannelongue, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie thoracique, Centre Chirurgical Marie Lannelongue (CCML)
Rok vydání: 2015
Předmět:
Zdroj: The Journal of Heart and Lung Transplantation
The Journal of Heart and Lung Transplantation, Elsevier, 2015, 34 (3), pp.457-467. ⟨10.1016/j.healun.2014.07.005⟩
ISSN: 1053-2498
DOI: 10.1016/j.healun.2014.07.005
Popis: Pulmonary microvascular disease (PMD) develops in both occluded and non-occluded territories in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and may cause persistent pulmonary hypertension after pulmonary endarterectomy. Endothelin-1 (ET-1) and interleukin-6 (IL-6) are potential PMD severity biomarkers, but it remains unknown whether they are related to occluded or non-occluded territories. We assessed PMD and ET-1/IL-6 gene expression profiles in occluded and non-occluded territories with and without chronic lung reperfusion in an animal CTEPH model.Chronic PH was induced in 10 piglets by left pulmonary artery (PA) ligation followed by weekly embolization of right lower lobe arteries with enbucrilate tissue adhesive for 5 weeks. At Week 6, 5 of 10 animals underwent left PA reperfusion. At Week 12, animals with and without reperfusion were compared with sham animals (n = 5). Hemodynamics, lung morphometry and ET-1/IL-6 gene expression profiles were assessed in the left lung (LL, occluded territories) and right upper lobe (RUL, non-occluded territories).At Week 12, mean PA pressure remained elevated without reperfusion (29.0 ± 2.8 vs 27.0 ± 1.1 mm Hg, p = 0.502), but decreased after reperfusion (30.0 ± 1.5 vs 20.5 ± 1.7 mm Hg, p = 0.013). Distal media thickness in the LL and RUL PAs and systemic vasculature to the LL were significantly lower in the reperfused and sham groups compared with the non-reperfused group. PMD progression was related to ET-1 and IL-6 gene expression in the RUL and to the ET-A/ET-B gene expression ratio in the LL.PMD regressed in occluded and non-occluded territories after lung reperfusion. Changes in ET-1 and IL-6 gene expression were associated with PMD in non-occluded territories.
Databáze: OpenAIRE