The differential effect of inspiratory, expiratory and combined resistive loading on healthy rat lung

Combined inspiratory and expiratory resistive breathing (CRB) is the landmark of obstructive airway disease. Inspiratory loading and CRB via tracheal banding are known to induce acute lung injury in previously healthy animals. The role of expiratory resistance remains unknown.Aim: To elucidate the differential effect of inspiratory, expiratory and combined resistive loading on healthy rat lung mechanics and inflammatory status and establish the lowest loads required to induce injury.Anesthetized tracheostomized wistar rats breathed through a two-way valve. A resistance was connected to the inspiratory, expiratory or both ports, so that measured peak inspiratory pressure was modulated to (IRB) 20-40% of maximum or peak expiratory to (ERB) 30-70%. Combined resistive breathing was studied in inspiratory/expiratory pressures of 30%/50%, 40%/50% and 40%/60% of maximum. Quietly breathing animals served as controls. At six hours, respiratory system mechanics were measured and bronchoalveolar lavage (BAL) was performed for cell and protein concentration counting. Both IRB and CRB increased tissue elasticity, BAL total cell, macrophage and neutrophil counts and protein content in a dose dependent manner. IRB 30% and CRB 40%/50% were identified as the lowest loads able to induce significant mechanical distortion and lung inflammation. ERB failed to induce significant changes, with the exception of BAL fluid neutrophilia. IRB and CRB, above 30% and 40%/50% respectively, dose-dependently derange mechanics, increase permeability and induce inflammation in healthy rats. ERB is a putative per se inflammatory stimulus for the lung.