Systemic Administration of FC-77 Dampens Ischemia–Reperfusion-Induced Acute Lung Injury in Rats

Abstract

Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia-reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-α and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-κB activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-κB activation and attenuation of subsequent inflammatory response.

Functional, Metabolic and Morphologic Results of Ex Vivo Donor Lung Perfusion with a Perfluorocarbon-Based Oxygen Carrier Nanoemulsion in a Large Animal Transplantation Model

“…Chu et al used an isolated rat lung perfusion model to demonstrate the beneficial effects of systemic PFC administration on ischemia reperfusion injury 40 . This effect was explained by the inhibition of NF-kB activity, inflammatory reactions and neutrophil infiltration into the lung tissue [40]. Systemic administration of PFC reduced phorbol myristate acetate-induced acute lung injury [61].…”

“…The anti-inflammatory effects of PFCs either by direct modulation of inflammatory cell function or attenuation of the production of inflammatory mediators have been reported [ 40 , 41 , 42 , 43 , 44 ]. In our experiments, we also observed an anti-inflammatory effect.…”

“…Oxygen dissolved in PFC is immediately available to tissues with a high extraction ratio [ 36 , 37 ]. In addition, several studies have suggested that systemic administration of PFC emulsion has anti-inflammatory effects [ 40 , 41 , 42 , 43 , 44 , 45 ].…”

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

“…Current lung machine perfusion assessment before transplantation are performed at normothermia but subnormothermic perfusion evaluation are already in standard clinical use for several solid organs [ 9 , 14 , 27 , 28 , 29 , 30 ]. It has been recently demonstrated that PFCOC are useful in lung surfactant therapy [ 31 ] and that the systemic administration of PFCOC may have potent anti-inflammatory effects in vivo [ 19 , 20 , 21 ], ex vivo [ 22 ], and in vitro [ 23 , 24 ]. Recently, we also demonstrated with a lung transplantation large animal model the benefits of using PFCOC with normothermic EVLP [ 22 ].…”

“…With PFCOC present in the lung microcapillaries, the oxygen is released and the carbon dioxide is picked up. In addition, the systemic administration of PFCOC may have potent anti-inflammatory effects in vivo [ 19 , 20 , 21 ] ex vivo [ 22 ] and in vitro [ 23 , 24 ].…”