Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

BACKGROUND: The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). METHODS: The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. RESULTS: The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). CONCLUSIONS: In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation

Spontaneous labour at term is associated with fetal monocyte activation

The aetiology of both term and preterm labour remains incompletely understood. Maternal infectious diseases as well as intra-uterine infections were shown to be a well established cause of uncontrollable preterm delivery, indicating that inflammatory reactions, regulated by maternal immunecompetent cells, are implicated in labour-promoting mechanisms. To investigate the possibility that the activation of the fetal immune system may be involved in labour induction, we examined cytokine production patterns of different cord blood cell populations obtained from neonates after spontaneous onset of normal term labour and vaginal delivery (n = 25), vaginal delivery but induced term labour (n = 17), and preterm delivery because of uncontrollable labour (n = 27, 20 patients received corticoid treatment for fetal lung maturation), in comparison with cells obtained from neonates after elective term caesarean delivery in the absence of labour (n = 15). Our results demonstrate that spontaneous term labour, but not induced term labour, was associated with significantly increased IL-6 production by myelomonocytic cell populations. Preterm delivery due to uncontrollable labour with resistance to tocolysis was not associated with increased IL-6 production by fetal myelomonocytic cells. Two-colour flow cytometry combined with intracellular cytokine staining was used to identify fetal monocytes as sources of labour-associated IL-6 release at term. We did not find any activation of cord blood T cells in association with spontaneous term or uncontrollable preterm labour. Therefore, fetal T cell responses may not cause monocyte activation. Our results suggest that increased release of IL-6 from fetal monocytes is involved in mechanisms promoting normal term, but not preterm labour, and that mechanisms inducing term and preterm labour are completely different