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 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.

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 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 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 The use of pulse pressure variation for predicting impairment of microcirculatory blood flow

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph R. Behem ◽  
Michael F. Graessler ◽  
Till Friedheim ◽  
Rahel Kluttig ◽  
Hans O. Pinnschmidt ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Reperfusion Injury ◽  
Pulse Pressure ◽  
Pulse Pressure Variation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pressure Variation ◽  
Volume Loading ◽  
Microcirculatory Blood Flow

AbstractDynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg−1 bodyweight−1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min−1) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p < 0.001, pulse pressure variation (%) 24.84 (17.45–32.22) versus 9.59 (1.68–17.49), p = 0.004, mean Flux (p.u.) 414.95 (295.18–534.72) versus 327.21 (206.95–447.48), p = 0.006. Receiver operating characteristic analysis revealed an area under the curve of 0.88 (CI 95% 0.73–1.00; p value < 0.001) for pulse pressure variation for predicting a decrease of microcirculatory blood flow. The results of our study show that pulse pressure variation does have the potential to predict decreases of intestinal microcirculatory blood flow due to volume-load after ischemia/reperfusion-injury. This should encourage further translational research and might help to prevent microcirculatory impairment due to excessive fluid resuscitation and to guide fluid therapy in the future.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

2006 ◽  
Vol 290 (3) ◽  
pp. C719-C727 ◽  
Author(s):  
Frank C. Chen ◽  
Ozgur Ogut
Keyword(s):  
Reperfusion Injury ◽  
Posttranslational Modifications ◽  
Actin Polymerization ◽  
Time Course ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Concentration ◽  
Cross Sectional ◽  
The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

CCR2 Deficiency Attenuates Ischemia Reperfusion Injury After Lung Transplantation

2011 ◽  
Vol 165 (2) ◽  
pp. 331
Author(s):  
R.G. Nava ◽  
A.C. Bribriesco ◽  
W. Li ◽  
A.E. Gelman ◽  
A.S. Krupnick ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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