Longitudinal quantification of radical bursts during pulmonary ischaemia and reperfusion

Gielis, Jan F.; Boulet, Gaëlle; Briedé, Jacob J.; Horemans, Tessa; Debergh, Tom; Kusse, Max; Cos, Paul; Schil, Paul Van

doi:10.1093/ejcts/ezu518

Cited by 31 publications

(35 citation statements)

References 21 publications

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“…EPR measurements were carried out on a Bruker EMX 1273 spectrometer equipped with an ER 4119HS high-sensitivity resonator and 12-kW power supply operating at X band frequencies. [ 23 ] The EPR analysis setting were as follows: frequency 9.86 GHz, power 50.41 mW, modulation frequency 100 kHz, modulation amplitude 1 G, sweep time 41.94 sec, time constant 40.96 msec, sweep width 50 G, number of scans 1. For the measurements, maternal blood was obtained at 9–11 weeks (mean 10+3 weeks), 24–28 weeks (mean 25+2 weeks) and at 38–41 weeks (mean 39+3weeks) in a heparin tube (BD vacutainer ® , Canada) and transported on ice.…”

Section: Methodsmentioning

confidence: 99%

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Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function

et al. 2018

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BackgroundDuring normal pregnancy, placental oxidative stress (OS) is present during all three trimesters and is necessary to obtain normal cell function. However, if OS reaches a certain level, pregnancy complications might arise. In preeclampsia (PE), a dangerous pregnancy specific hypertensive disorder, OS induced in the ischemic placenta causes a systemic inflammatory response and activates maternal endothelial cells. In this study, we aimed to quantify superoxide concentrations (as a measure of systemic OS) using electron paramagnetic resonance (EPR) and correlate them to markers of systemic inflammation, iron status and vascular function.MethodsFifty-nine women with a healthy pregnancy (HP), 10 non-pregnant controls (NP) and 28 PE patients (32±3.3weeks) were included. During HP, blood samples for superoxide, neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV) and iron status were taken at 10, 25 and 39 weeks. Vascular measurements for arterial stiffness (carotid-femoral pulse wave velocity (CF-PWV), augmentation index (AIx), augmentation Pressure (AP)) and microvascular endothelial function (reactive hyperemia index (RHI)) were performed at 35 weeks. In PE, all measurements were performed at diagnosis. CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) was used as spin probe for EPR, since the formed CM radical corresponds to the amount of superoxide.ResultsSuperoxide concentration remains stable during pregnancy (p = 0.92), but is significantly higher compared to the NP controls (p<0.0001). At 25 weeks, there is a significant positive correlation between superoxide and ferritin concentration. (p = 0.04) In PE, superoxide, systemic inflammation and iron status are much higher compared to HP (all p<0.001). During HP, superoxide concentrations correlate significantly with arterial stiffness (all p<0.04), while in PE superoxide is significantly correlated to microvascular endothelial function (p = 0.03).ConclusionsDuring HP there is an increased but stable oxidative environment, which is correlated to ferritin concentration. If superoxide levels increase, there is an augmentation in arterial stiffness. In PE pregnancies, systemic inflammation and superoxide concentrations are higher and result in a deterioration of endothelial function. Together, these findings support the hypothesis that vascular function is directly linked to the amount of OS and that measurement of OS in combination with vascular function tests might be used in the prediction of PE.

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Section: Methodsmentioning

confidence: 99%

“…The sample was snap frozen and stored at -80°C until analysis. [ 23 ] The concentrations reported were obtained via double integration of the respective simulated spectra of the formed CM radical and this corresponds to the amount of superoxide that was present in the sample. The simulations were performed using a NIEHS P.E.S.T.…”

Section: Methodsmentioning

confidence: 99%

Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function

et al. 2018

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“…Starting from 1 hour after reperfusion, there are reportedly significant increases of superoxide, NO, and their reaction products, which participate in ischemia-reperfusion injury pathogenesis, and free radical bursts can be found in the peripheral blood 1 hour after the start of ischemia. [ 34 ] Although the half-life of iloprost is only 20 to 30 min, the effects of cAMP induced by iloprost are maintained for 4 hours; [ 35 ] therefore, we can postulate that inhaled iloprost administered directly after reperfusion of the grafted lung both suppressed the immediate response of lung ischemia-reperfusion injury and delayed the dissemination of radical bursts. During pulmonary vasodilation by means of inhaled iloprost, inhaled cAMP increases reabsorption of alveolar leakage, which decreases intra-alveolar edema and ameliorates dissemination of radical bursts, starting from perfusion of the grafted lung.…”

Section: Discussionmentioning

confidence: 99%

Effects of intraoperative inhaled iloprost on primary graft dysfunction after lung transplantation

Lee¹,

Lee²,

Lee³

et al. 2016

Medicine

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Design:Inhaled iloprost was known to alleviate ischemic-reperfusion lung injury. We investigated whether intraoperative inhaled iloprost can prevent the development of primary graft dysfunction after lung transplantation. Data for a consecutive series of patients who underwent lung transplantation with extracorporeal membrane oxygenation were retrieved. By propensity score matching, 2 comparable groups of 30 patients were obtained: patients who inhaled iloprost immediately after reperfusion of the grafted lung (ILO group); patients who did not receive iloprost (non-ILO group).Results:The severity of pulmonary infiltration on postoperative days (PODs) 1 to 3 was significantly lower in the ILO group compared to the non-ILO group. The PaO2/FiO2 ratio was significantly higher in the ILO group compared to the non-ILO group (318.2 ± 74.2 vs 275.9 ± 65.3 mm Hg, P = 0.022 on POD 1; 351.4 ± 58.2 vs 295.8 ± 53.7 mm Hg, P = 0.017 on POD 2; and 378.8 ± 51.9 vs 320.2 ± 66.2 mm Hg, P = 0.013 on POD 3, respectively). The prevalence of the primary graft dysfunction grade 3 was lower in the ILO group compared to the non-ILO group (P = 0.042 on POD 1; P = 0.026 on POD 2; P = 0.024 on POD 3, respectively). The duration of ventilator use and intensive care unit were significantly reduced in the ILO group (P = 0.041 and 0.038).Conclusions:Intraoperative inhaled iloprost could prevent primary graft dysfunction and preserve allograft function, thus reducing the length of ventilator care and intensive care unit stay, and improving the overall early post-transplant morbidity in patients undergoing lung transplantation.

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“…Most of these responses are initiated by rapid and robust generation of ROS that leads to cell/tissue injury, activation of multiple cell types, lipid membrane peroxidation and secretion of inflammatory cytokines and DAMPs (De Perrot et al, 2002;Andrade et al, 2006;Kreisel et al, 2010;Ferrari and Andrade, 2015;Laubach and Sharma, 2016;Zheng et al, 2017;Tatham et al, 2018). The activation and infiltration of innate immune cells, especially neutrophils into the graft during reperfusion is a key aspect of I/R injury largely driven by chemokines and ROS produced by donor lung cells such as epithelium, endothelium or macrophages that were injured and/or activated (Kobayashi, 2008;Gielis et al, 2015;Merry et al, 2015). Complications associated with increased ischemic time and reperfusion injury of transplanted lung grafts are responsible for decreasing the number of donor lungs suitable for transplantation and increasing the rate of primary lung graft failure and dysfunction (Christie et al, 2005;Diamond et al, 2013;Wang et al, 2019).…”

Section: Shear Stress In the Lung Vasculaturementioning

confidence: 99%

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

Dorrello

Vunjak‐Novakovic

2020

Front. Bioeng. Biotechnol.

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The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We review recent advances in lung bioengineering that have potential to repair the epithelial and vascular compartments of the lung. Our focus is on the long-term support and recovery of the lung ex vivo, and the replacement of defective epithelium with healthy therapeutic cells. To this end, we first review the roles of the lung epithelium and vasculature, with focus on the alveolar-capillary membrane, and then discuss the available and emerging technologies for ex vivo bioengineering of the lung by decellularization and recellularization. While there have been many meritorious advances in these technologies for recovering marginal quality lungs to the levels needed to meet the standards for transplantation -many challenges remain, motivating further studies of the extended ex vivo support and interventions in the lung. We propose that the repair of injured epithelium with preservation of quiescent vasculature will be critical for the immediate blood supply to the lung and the lung survival and function following transplantation.

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Longitudinal quantification of radical bursts during pulmonary ischaemia and reperfusion

Cited by 31 publications

References 21 publications

Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function

Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function

Effects of intraoperative inhaled iloprost on primary graft dysfunction after lung transplantation

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

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