Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs

Abstract

The authors investigated the protective effects and dose dependency of perfluorohexane (PFH) vapor on leukocyte-mediated lung injury in isolated, perfused, and ventilated rabbit lungs. Lungs received either 18 vol.% (n = 7), 9 vol.% (n = 7), or 4.5 vol.% (n = 7) PFH. Fifteen minutes after beginning of PFH application, lung injury was induced with formyl-Met-Leu-Phe (fMLP). Control lungs (n = 7) received fMLP only. In addition 5 lungs (PFH-sham) remained uninjured receiving 18 vol.% PFH only. Pulmonary artery pressure (mPAP), peak inspiratory pressure (P(max)), and lung weight were monitored for 90 minutes. Perfusate samples were taken at regular intervals for analysis and representative lungs were fixed for histological analysis. In the control, fMLP application led to a significant increase of mPAP, P(max), lung weight, and lipid mediators. Pretreatment with PFH attenuated the rise in these parameters. This was accompanied by preservation of the structural integrity of the alveolar architecture and air-blood barrier. In uninjured lungs, mPAP, P(max), lung weight, and lipid mediator formation remained uneffected in the presence of PFH. The authors concluded that pretreatment with PFH vapor leads to an attenuation of leukocyte-mediated lung injury. Vaporization of perfluorocarbons (PFCs) offers new therapeutic options, making use of their protective and anti-inflammatory properties in prophylaxis or in early treatment of acute lung injury.

Use of nonhuman primates in obstructive lung disease research – is it required?

“…Whereas data for most of these monoclonal antibodies regarding nonhuman primate studies are not available, tralokinumab significantly inhibited BAL eosinophils and reduced AHR in a cynomolgus Ascaris model of asthma and also in a humanized mouse model (May et al, 2012). Reduction of BAL eosinophils in cynomolgus macaques was also observed in anrukinzumab (Bree et al, 2007), whereas human patients with persistent asthma did not improve upon treatment. In patients with mild atopic asthma, lung function improved by using anrukinzumab, but sputum eosinophils were not reduced (Gauvreau et al, 2011), indicating the need to carefully select patients and endpoints.…”

Garcinia Multiflora Inhibits FPR1-Mediated Neutrophil Activation and Protects Against Acute Lung Injury

“…N-formyl peptides may facilitate neutrophil mobilization and recruitment to sites of inflammation, resulting in lung damage [34,35]. Chemotaxis and the migration of fMLF- [36].…”