Impact of respiratory pattern on lung mechanics and interstitial proteoglycans in spontaneously breathing anaesthetized healthy rats

Aim: The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix. Methods: Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaesthetic mixtures: pentobarbital/urethane (P/U) and ketamine/medetomidine (K/M). The animals (five per group) were randomized and left to spontaneously breath for 10 min (P/U-sham; K/M-sham) or for 4 h (P/U-4 h; K/M-4 h), targeting the anaesthesia level to obtain a tidal volume of about 8 mL kg(-1) body wt. At the end of the experiment, lung matrix integrity was assessed through determination of the glycosaminoglycans (GAGs) content in the lung parenchyma. Results: Compared with K/M, anaesthesia with P/U cocktail induced: (1) a higher respiratory rate and minute ventilation attained with lower PaCO2; (2) a higher pressure-time-product and work of breathing per minute; (3) a lower static lung compliance; (4) an increased activation of lung tissue metalloproteases; and (5) greater extraction of pulmonary interstitial GAGs. Conclusions: This study suggests that the breathing pattern induced by the different anaesthetic regimen may damage the pulmonary interstitium even during spontaneous breathing at physiological tidal volumes.