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Our aim was to develop a computerized system for real-time monitoring of lung mechanics measurements during both gas and liquid ventilation. System accuracy was demonstrated by calculating regression and percent error of the following parameters compared to standard device: airway pressure difference (DeltaPaw), respiratory frequency (fR ), tidal volume (VT), minute ventilation (V'E), inspiratory and expiratory maximum flows (V'ins,max, V'exp,max), dynamic lung compliance (CL,dyn), resistance of the respiratory system calculated by method of Mead-Whittenberger (Rrs,MW) and by equivalence to electrical circuits (Rrs,ele), work of breathing (WOB), and overdistension. Outcome measures were evaluated as function of gas exchange, cardiovascular parameters, and lung mechanics including mean airway pressure (mPaw). DeltaPaw, VT, V'ins,max, V'exp,max, and V'E measurements had correlation coefficients r = 1.00, and %error < 0.5%. fR, CL,dyn, Rrs,MW, Rrs,ele, and WOB showed r ges 0.98 and %error < 5%. Overdistension had r = 0.87 and %error < 15%. Also, resistance was accurately calculated by a new algorithm. The system was tested in rats in which lung lavage was used to induce acute respiratory failure. After lavage, both gas- and liquid-ventilated groups had increased mPaw and WOB, with decreased VT, V'E, CL,dyn, Rrs,MW, and Rrs,ele compared to controls. After 1-h ventilation, both injured group had decreased VT, V'E, and CL,dyn, with increased mPaw, Rrs,MW, Rrs,ele, and WOB. In lung-injured animals, liquid ventilation restored gas exchange, and cardiovascular and lung function- - s. Our lung mechanics system was able to closely monitor pulmonary function, including during transitions between gas and liquid phases.