A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation

Abstract Background Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow i...

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Main Authors: Anna Elisabeth Frick, Michaela Orlitová, Arno Vanstapel, Sofie Ordies, Sandra Claes, Dominique Schols, Tobias Heigl, Janne Kaes, Berta Saez-Gimenez, Robin Vos, Geert M. Verleden, Bart Vanaudenaerde, Stijn E. Verleden, Dirk E. Van Raemdonck, Arne P. Neyrinck
Format: Article
Language:English
Published: SpringerOpen 2021-02-01
Series:Intensive Care Medicine Experimental
Subjects:
Online Access:https://doi.org/10.1186/s40635-021-00371-1
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spelling doaj-61ba9a7e658b4ca3b6b58792f683221d2021-02-07T12:51:30ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2021-02-019111510.1186/s40635-021-00371-1A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantationAnna Elisabeth Frick0Michaela Orlitová1Arno Vanstapel2Sofie Ordies3Sandra Claes4Dominique Schols5Tobias Heigl6Janne Kaes7Berta Saez-Gimenez8Robin Vos9Geert M. Verleden10Bart Vanaudenaerde11Stijn E. Verleden12Dirk E. Van Raemdonck13Arne P. Neyrinck14Department of Cardiovascular Sciences, KU LeuvenDepartment of Cardiovascular Sciences, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenDepartment of Cardiovascular Sciences, KU LeuvenLaboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU LeuvenLaboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenBREATHE, Department of Chronic Diseases, Metabolism and Ageing (Chrometa), Leuven Lung Transplant Unit, KU LeuvenDepartment of Cardiovascular Sciences, KU LeuvenAbstract Background Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model. Materials Twelve porcine left lung transplants were divided in two groups (n = 6, in low- (LF) and high-flow (HF) group). Donor lungs were stored for 24 h on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6 h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40–60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped. Results Survival at 6 h was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 h of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia–reperfusion injury. Conclusions Partial clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extracorporeal devices and represent a specific intra-operative problem during bilateral sequential single-lung transplantation.https://doi.org/10.1186/s40635-021-00371-1Porcine left lung transplantationPrimary graft dysfunctionPulmonary vascular resistance
collection DOAJ
language English
format Article
sources DOAJ
author Anna Elisabeth Frick
Michaela Orlitová
Arno Vanstapel
Sofie Ordies
Sandra Claes
Dominique Schols
Tobias Heigl
Janne Kaes
Berta Saez-Gimenez
Robin Vos
Geert M. Verleden
Bart Vanaudenaerde
Stijn E. Verleden
Dirk E. Van Raemdonck
Arne P. Neyrinck
spellingShingle Anna Elisabeth Frick
Michaela Orlitová
Arno Vanstapel
Sofie Ordies
Sandra Claes
Dominique Schols
Tobias Heigl
Janne Kaes
Berta Saez-Gimenez
Robin Vos
Geert M. Verleden
Bart Vanaudenaerde
Stijn E. Verleden
Dirk E. Van Raemdonck
Arne P. Neyrinck
A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
Intensive Care Medicine Experimental
Porcine left lung transplantation
Primary graft dysfunction
Pulmonary vascular resistance
author_facet Anna Elisabeth Frick
Michaela Orlitová
Arno Vanstapel
Sofie Ordies
Sandra Claes
Dominique Schols
Tobias Heigl
Janne Kaes
Berta Saez-Gimenez
Robin Vos
Geert M. Verleden
Bart Vanaudenaerde
Stijn E. Verleden
Dirk E. Van Raemdonck
Arne P. Neyrinck
author_sort Anna Elisabeth Frick
title A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
title_short A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
title_full A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
title_fullStr A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
title_full_unstemmed A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
title_sort novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation
publisher SpringerOpen
series Intensive Care Medicine Experimental
issn 2197-425X
publishDate 2021-02-01
description Abstract Background Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model. Materials Twelve porcine left lung transplants were divided in two groups (n = 6, in low- (LF) and high-flow (HF) group). Donor lungs were stored for 24 h on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6 h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40–60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped. Results Survival at 6 h was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 h of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia–reperfusion injury. Conclusions Partial clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extracorporeal devices and represent a specific intra-operative problem during bilateral sequential single-lung transplantation.
topic Porcine left lung transplantation
Primary graft dysfunction
Pulmonary vascular resistance
url https://doi.org/10.1186/s40635-021-00371-1
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