scholarly journals Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Alessandro Bertani ◽  
Vitale Miceli ◽  
Lavinia De Monte ◽  
Giovanna Occhipinti ◽  
Valeria Pagano ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Outcome Analysis ◽  
Swine Model ◽  
Cold Ischemia ◽  
Tissue Samples

Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients’ data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.

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

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Elisabeth Frick ◽  
Michaela Orlitová ◽  
Arno Vanstapel ◽  
Sofie Ordies ◽  
Sandra Claes ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Right Pulmonary Artery ◽  
The Right ◽  
The Impact

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.

scholarly journals Lung Inflation With Hydrogen During the Cold Ischemia Phase Alleviates Lung Ischemia-Reperfusion Injury by Inhibiting Pyroptosis in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Zheng ◽  
Jiyu Kang ◽  
Entong Xing ◽  
Bin Zheng ◽  
Xueyao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Sham Group ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cold Ischemia ◽  
Lung Inflation

Background: Lung inflation with hydrogen is an effective method to protect donor lungs from lung ischemia-reperfusion injury (IRI). This study aimed to examine the effect of lung inflation with 3% hydrogen during the cold ischemia phase on pyroptosis in lung grafts of rats.Methods: Adult male Wistar rats were randomly divided into the sham group, the control group, the oxygen (O2) group, and the hydrogen (H2) group. The sham group underwent thoracotomy but no lung transplantation. In the control group, the donor lungs were deflated for 2 h. In the O2 and H2 groups, the donor lungs were inflated with 40% O2 + 60% N2 and 3% H2 + 40% O2 + 57% N2, respectively, at 10 ml/kg, and the gas was replaced every 20 min during the cold ischemia phase for 2 h. Two hours after orthotopic lung transplantation, the recipients were euthanized.Results: Compared with the control group, the O2 and H2 groups improved oxygenation indices, decreases the inflammatory response and oxidative stress, reduced lung injury, and improved pressure-volume (P-V) curves. H2 had a better protective effect than O2. Furthermore, the levels of the pyroptosis-related proteins selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase)-1 p20, and the N-terminal of gasdermin D (GSDMD-N) were decreased in the H2 group.Conclusion: Lung inflation with 3% hydrogen during the cold ischemia phase inhibited the inflammatory response, oxidative stress, and pyroptosis and improved the function of the graft. Inhibiting reactive oxygen species (ROS) production may be the main mechanism of the antipyroptotic effect of hydrogen.

scholarly journals Creatine Supply Attenuates Ischemia-Reperfusion Injury in Lung Transplantation in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2765
Author(s):  
Francine M. Almeida ◽  
Angela S. Battochio ◽  
João P. Napoli ◽  
Katiusa A. Alves ◽  
Grace S. Balbin ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Immune System Activation

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

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

2020 ◽  
Author(s):  
Anna Elisabeth Frick ◽  
Michaela Orlitová ◽  
Arno Vanstapel ◽  
Sofie Ordies ◽  
Sandra Claes ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Pulmonary Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Right Pulmonary Artery ◽  
The Right ◽  
The Impact

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 PA 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 development of ischemia reperfusion is feasible. This allows the study of pulmonary flow as a contributor in the process of ischemia-reperfusion injury. Our findings might impact future studies with extra-corporeal devices and represents a specific intra-operative problem during bilateral sequential single lung transplantation.

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

2021 ◽  
Author(s):  
Anna Elisabeth Frick ◽  
Michaela Orlitová ◽  
Arno Vanstapel ◽  
Sofie Ordies ◽  
Sandra Claes ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Right Pulmonary Artery ◽  
The Right ◽  
The Impact

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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