Deep inflations maintain surfactant function and alveolar fluid balance in lungs with reduced surfactant protein B levels during mechanical ventilation

Surfactant protein B (SP-B) is essential for surface tension reducing function of pulmonary surfactant and alveolar unfolding processes during inspiration. SP-B is reduced early in acute lung injury. Hence, we hypothesize that <i>1</i>) reduced SP-B expression increases susceptibility to ventilation-induced lung injury (VILI), and <i>2</i>) deep inflations (DI) are protective against VILI. Conditional SP-B knockout mice were randomized into OFF (reduced SP-B) and ON groups (normal SP-B) and subjected to mechanical ventilation at zero end-expiratory pressure. Over 4 h of ventilation, either 4 or 16 DI were administered. Lung mechanics were recorded, and pulmonary structure was quantified by design-based stereology. Inflammatory cells and bulk RNA sequencing were measured in bronchoalveolar lavage (BAL) and tissue, respectively. No differences in inflammatory cells in BAL were detected between ON and OFF groups. During ventilation, alveolar derecruitment-related increase in elastance was most pronounced in OFF-4DI but reversible by DI so that lung mechanics did not worsen. Finally, volumes of the alveolar liquid lining layer and the intracellular surfactant were largest, whereas the surface area of the apical plasma membrane of type II pneumocytes was smallest in OFF-4DI, suggesting impaired surfactant secretion. A higher frequency of DI prevented these abnormalities. Electron microscopy revealed disorganized tight junctions between alveolar epithelial cells in OFF-4DI, which was linked with decreased expression of genes relevant to the apical junctional complex. Reduced SP-B resulted in a progressive increase in surface tension and a disturbed fluid balance without triggering definite VILI. Maintenance of residual surfactant function is highly dependent on DI in conditions of reduced SP-B levels.<b>NEW & NOTEWORTHY</b> Surfactant protein B (SP-B) is critical for efficient surfactant function in the lung. Reduced SP-B levels occur at an early stage of acute lung injury and impair alveolar unfolding. In this study, we demonstrate that mechanical ventilation of lungs with reduced SP-B levels does not trigger ventilation-induced lung injury but results in disbalance of alveolar fluid volume and increase in surface tension due to failure of surfactant maintenance. Deep inflations prevent these ventilation-induced effects.