BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstricting mitogen that has been implicated in the development of primary graft dysfunction. Increased activity of matrix metalloproteinases (MMPs), specifically MMP-2 and -9, has been associated with tissue damage in acute lung injury and after lung transplantation. Using a validated model of brain-stem death (BSD), we aimed to determine whether alveolar macrophage up-regulation in the pulmonary system is an early feature of BSD injury and if expression levels of ET-1, endothelin A receptors (ET(A)R) and endothelin B receptors (ET(B)R), as well as MMP-2 and -9, are increased in comparison to sham controls. METHODS: Six control and 8 experimental Wistar-Kyoto rats had a balloon catheter inserted into their subdural space. In the experimental group the balloon was inflated for 4 hours. Lung specimens were immunohistochemically labeled with CD68, ET-1, ET(A)R, ET(B)R, MMP-2 and MMP-9, and 10 fields per slide were assessed. RESULTS: The ratio of alveolar macrophages to polymorphonuclear neutrophils was significantly greater in the BSD group than in controls (9 +/- 4.1 vs 3 +/- 0.5, p = 0.004) and adventitial macrophages increased in BSD lung parenchyma (p < 0.0001). ET-1, ET(A)R and ET(B)R levels were elevated in the experimental group (27.6 +/- 5.7 vs 7 +/- 2.3, 36.1 +/- 4.6 vs 17.7 +/- 2.6 and 60 +/- 7.1 vs 19.8 +/- 3.7, p < 0.0001 inclusive). BSD expression of MMP-2 and MMP-9 was double that of controls (14.9 +/- 3.4 vs 30.7 +/- 3.4 and 14.2 +/- 2.2 vs 37 +/- 3.6, respectively, p < 0.0001 inclusive). CONCLUSIONS: Alveolar macrophages are rapidly recruited after BSD and may affect peri-operative lung function via increased expression of ET-1, ET(A)R, ET(B)R, MMP-2 and MMP-9.
BACKGROUND:Endothelin-1 (ET-1) is a potent vasoconstricting mitogen that has been implicated in the development of primary graft dysfunction. Increased activity of matrix metalloproteinases (MMPs), specifically MMP-2 and -9, has been associated with tissue damage in acute lung injury and after lung transplantation. Using a validated model of brain-stem death (BSD), we aimed to determine whether alveolar macrophage up-regulation in the pulmonary system is an early feature of BSD injury and if expression levels of ET-1, endothelin A receptors (ET(A)R) and endothelin B receptors (ET(B)R), as well as MMP-2 and -9, are increased in comparison to sham controls. METHODS: Six control and 8 experimental Wistar-Kyoto rats had a balloon catheter inserted into their subdural space. In the experimental group the balloon was inflated for 4 hours. Lung specimens were immunohistochemically labeled with CD68, ET-1, ET(A)R, ET(B)R, MMP-2 and MMP-9, and 10 fields per slide were assessed. RESULTS: The ratio of alveolar macrophages to polymorphonuclear neutrophils was significantly greater in the BSD group than in controls (9 +/- 4.1 vs 3 +/- 0.5, p = 0.004) and adventitial macrophages increased in BSD lung parenchyma (p < 0.0001). ET-1, ET(A)R and ET(B)R levels were elevated in the experimental group (27.6 +/- 5.7 vs 7 +/- 2.3, 36.1 +/- 4.6 vs 17.7 +/- 2.6 and 60 +/- 7.1 vs 19.8 +/- 3.7, p < 0.0001 inclusive). BSD expression of MMP-2 and MMP-9 was double that of controls (14.9 +/- 3.4 vs 30.7 +/- 3.4 and 14.2 +/- 2.2 vs 37 +/- 3.6, respectively, p < 0.0001 inclusive). CONCLUSIONS: Alveolar macrophages are rapidly recruited after BSD and may affect peri-operative lung function via increased expression of ET-1, ET(A)R, ET(B)R, MMP-2 and MMP-9.
Authors: Doris A Chatfield; Darshan H Brahmbhatt; Tilly Sharp; Iain E Perkes; Joanne G Outrim; David K Menon Journal: Neurocrit Care Date: 2011-02 Impact factor: 3.210
Authors: Ryan P Watts; Izabela Bilska; Sara Diab; Kimble R Dunster; Andrew C Bulmer; Adrian G Barnett; John F Fraser Journal: Intensive Care Med Exp Date: 2015-11-24
Authors: K Walweel; K Skeggs; A C Boon; L E See Hoe; M Bouquet; N G Obonyo; S E Pedersen; S D Diab; M R Passmore; K Hyslop; E S Wood; J Reid; S M Colombo; N J Bartnikowski; M A Wells; D Black; L P Pimenta; A K Stevenson; K Bisht; L Marshall; D A Prabhu; L James; D G Platts; P S Macdonald; D C McGiffin; J Y Suen; J F Fraser Journal: J Biomed Sci Date: 2020-10-02 Impact factor: 8.410