Perfluorocarbon induces alveolar epithelial cell response through structural and mechanical remodeling.

During total liquid ventilation, lung cells are exposed to perfluorocarbon (PFC) whose chemophysical properties highly differ from standard aqueous cell feeding medium (DMEM). We herein perform a systematic study of structural and mechanical properties of A549 alveolar epithelial cells in order to characterize their response to PFC exposure, using DMEM as control condition. Changes in F-actin structure, focal adhesion density and glycocalyx distribution are evaluated by confocal fluorescent microscopy. Changes in cell mechanics and adhesion are measured by multiscale magnetic twisting cytometry (MTC). Two different microrheological models (single Voigt and power law) are used to analyze the cell mechanics characterized by cytoskeleton (CSK) stiffness and characteristic relaxation times. Cell-matrix adhesion is analyzed using a stochastic multibond deadhesion model taking into account the non-reversible character of the cell response, allowing us to quantify the adhesion weakness and the number of associated bonds. The roles of F-actin structure and glycocalyx layer are evaluated by depolymerizing F-actin and degrading glycocalyx, respectively. Results show that PFC exposure consistently induces F-actin remodeling, CSK softening and adhesion weakening. These results demonstrate that PFC triggers an alveolar epithelial cell response herein evidenced by a decay in intracellular CSK tension, an adhesion weakening and a glycocalyx layer redistribution. These PFC-induced cell adjustments are consistent with the hypothesis that cells respond to a decrease in adhesion energy at cell surface. This adhesion energy can be even further reduced in the presence of surfactant adsorbed at the cell surface.

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest.

INTRODUCTION: Total liquid ventilation (TLV) can cool down the entire body within 10-15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest). METHODS: In a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency. RESULTS: Under physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC. CONCLUSION: Using a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.