title: Concomitant endothelin-1 overexpression in lung transplant donors and recipients predicts primary graft dysfunction.
abstract: Primary graft dysfunction (PGD) causes significant morbidity following lung transplantation (LTX). Mortality is high in PGD and therapeutic strategies are limited. To investigate whether endothelin-1 (ET-1) that mediates increased vascular permeability and edema formation in lung grafts can predict PGD, ET-1 mRNA expression was examined in lung tissue biopsies of 105 donors and recipients obtained shortly before LTX. Serum ET-1 concentration was assessed by ELISA. PGD grade was diagnosed and scored by oxygenation and radiological characteristics according to ISHLT guidelines. PGD grade 3 developed in 11% of patients. ET-1 mRNA expression was significantly increased in both donor (p < 0.0001) and recipient (p = 0.01) developing PGD as compared to no PGD group. Pretransplant ET-1 serum concentrations were elevated in recipients with PGD as compared to no PGD group (p < 0.0001), although serum ET-1 was not different between donors whose grafts developed PGD grades 0-3. In regression analysis, concomitant elevated donor tissue ET-1 and recipient serum ET-1 predicted PGD grade 3. This study indicates that pretransplant ET-1 mRNA overexpression in donors associated with elevated pretransplant serum ET-1 in recipients contribute to PGD development and that their assessment might be beneficial to predict PGD and to identify recipients who could benefit from a targeted ET-1 blockade.
authors.affiliation: Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Salama
authors.forename: O
authors.initials: O
authors.lastname: Andrukhova
authors.forename: M A
authors.initials: MA
authors.lastname: Hoda
authors.forename: S
authors.initials: S
authors.lastname: Taghavi
authors.forename: P
authors.initials: P
authors.lastname: Jaksch
authors.forename: G
authors.initials: G
authors.lastname: Heinze
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.forename: S
authors.initials: S
authors.lastname: Aharinejad
mesh_terms: D000328:Adult; D019332:Endothelin-1 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000209:etiology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger