2021Research SquareOpen access

A Novel Experimental Porcine Model to Assess the Impact of Differential Pulmonary Blood Flow on Ischemia-reperfusion Injury After Unilateral Lung Transplantation

Anna E. Frick, Michaela Orlitová, Arno Vanstapel, Sofie Ordies, Sandra Claes, Dominique Schols, Tobias Heigl, Janne Kaes, Berta Sáez, Robin Vos, Geert M. Verleden, Bart Vanaudenaerde, Stijn E. Verleden, Dirk Van Raemdonck, Arne Neyrinck

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Abstract

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 hours on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6h 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 hours was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 hours 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 extra-corporeal devices and represents a specific intra-operative problem during bilateral sequential single lung transplantation.

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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 hours on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6h 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 hours was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 hours 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 extra-corporeal devices and represents a specific intra-operative problem during bilateral sequential single lung transplantation.

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Available abstract

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 hours on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6h 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 hours was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 hours 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 extra-corporeal devices and represents a specific intra-operative problem during bilateral sequential single lung transplantation.

Key concepts: Reperfusion injury, Lung, Medicine, Blood flow, Transplantation, Ischemia, Lung transplantation, Cardiology

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A Novel Experimental Porcine Model to Assess the Impact of Differential Pulmonary Blood Flow on Ischemia-reperfusion Injury After Unilateral Lung Transplantation — Research Paper | ScholarLens