Perfluorocarbon-Based Oxygen Carriers and Subnormothermic Lung Machine Perfusion Decrease Production of Pro-Inflammatory Mediators

Abstract

The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a rat model, we evaluated on a 4 h EVLP time the effects of PFCOC with either 28 °C or 37 °C perfusion temperatures. During EVLP at 28 °C with PFCOC, we recorded significantly lower lung pulmonary vascular resistance (PVR), higher dynamic compliance (Cdyn), significantly lower potassium and lactate levels, higher lung tissue ATP content, and significantly lower myeloperoxidase tissue activity when compared to the 37 °C EVLP with PFCOC. In the subnormothermic EVLP with or without PFCOC, the pro-inflammatory mediator TNFα, the cytokines IL-6 and IL-7, the chemokines MIP-3α, MIP-1α, MCP-1, GRO/KC as well as GM-CSF, G-CSF and the anti-inflammatory cytokines IL-4 and IL-10 were significantly lower. The 28 °C EVLP improved both Cdyn and PVR and decreased pro-inflammatory cytokines and pCO2 levels compared to the 37 °C EVLP. In addition, the 28 °C EVLP with PFCOC produced a significantly lower level of myeloperoxidase activity in lung tissue. Subnormothermic EVLP with PFCOC significantly improves lung donor physiology and ameliorates lung tissue biochemical and inflammatory parameters.

Biomimetic Nanoarchitectonics of Hollow Mesoporous Copper Oxide-Based Nanozymes with Cascade Catalytic Reaction for Near Infrared-II Reinforced Photothermal-Catalytic Therapy

“…Previously, hyperbaric oxygen inhalation was regarded as a common medical strategy to alleviate tumor hypoxia. − However, oxygenation of hyperbaric blood is hampered by the inefficiency of microvascular systems in tumor tissue and superfluous systemic oxygen inhalation would induce the probable toxicity, which further limits its clinical application. , Nowadays, researchers have proposed some novel design ideas to increase the concentration of O 2 at the tumor sites, including the construction of appropriate O 2 conveyors such as perfluorocarbon or hemoglobin to transport O 2 directly to the tumor tissue ,− and suppressing cell respiration to improve the O 2 level, − which have obtained desirable outcomes in the animal experiments. Meantime, enzymes, such as the natural enzymes (catalase) and nanozymes (MnO 2 ), have been considered a new class of nanomedicine for in situ intratumoral oxygen generation.…”

Oxygen carriers affect kidney immunogenicity during ex-vivo machine perfusion

“…As already mentioned, several preclinical studies support the beneficial effects of alternative OCs in the field of ex-vivo organ perfusion (10,19,20,25,26,56,58). PFC-based OCs and M101 provide a high oxygen-carrying capacity and perform well in cell metabolism and histology with an amelioration of ischemiareperfusion injury (21,27).…”

The Effects of Free Heme on Functional and Molecular Changes During Ex Vivo Normothermic Machine Perfusion of Human Kidneys

“…Artificial oxygen carriers such as hemopure are an alternative to RBCs and are being trialled in kidney NMP ( 31 , 32 ). Subnormothermic temperatures or the combination of subnormothermic temperature and artificial oxygen carriers have recently been shown to reduce inflammation and pulmonary vascular resistance during ex vivo lung perfusion (EVLP) ( 33 ) and should be explored in kidney NMP.…”