Abstract Rationale In the acute respiratory distress syndrome (ARDS), treatment with mechanical ventilation is supportive but causes additional ventilation induced lung injury (VILI). In ARDS/VILI, injury is spatially heterogeneous with injured regions being diminished in size and having elevated alveolar capillary barrier (ACB) permeability. Proposed mechanisms of VILI include over-distension (OD) and cyclic recruitment/derecruitment (RD). Due to interdependence, healthy regions adjacent to diminished regions are overdistended. Thus, OD and RD are coupled. To decouple the two mechanisms, we ventilate healthy lungs with protocols that impose only OD or only RD across the parenchyma. We quantify ventilation-induced alteration of ACB permeability with a novel electrical method. Methods We work in excised lungs. In an IACUC-approved protocol, we anesthetize a rat, euthanize, perform a thoracotomy, ligate the pulmonary artery and aorta to preserve vascular volume and excise the lungs. In preliminary experiments under a dissecting microscope, we find an end-expiratory pressure of 1.5 cmH2O to prevent alveolar collapse. Working on the diaphragmatic surface, we puncture electrodes through the pleura. We inject a biphasic current across the ACB between one electrode in the liquid lining layer (LLL) of an alveolus and another in an arteriole or venule. With an oscilloscope, we record voltage between a third electrode, in the LLL of a neighboring alveolus, and the vascular electrode. We quantify phase difference, ΔV. At baseline, before ventilation, we determine ΔVBL in two areas. We then ventilate for one minute (pressure controlled, 30 min-1, 1:2 inspiratory:expiratory ratio). For maximal-physiologic, OD or RD ventilation, we vary pressure in the range: 3-30, 0-30 or 5-45 cmH2O, respectively. Post-ventilation, we determine ΔV in two additional areas. We divide ΔV from each post-ventilation area by average ΔVBL to obtain normalized metric ΔVnorm, which varies inversely with ACB permeability. Results We find that maximal-physiologic and OD ventilation do not alter ΔVnorm, but RD ventilation decreases ΔVnorm (Fig. 1). Conclusions We introduce new methods for characterizing local aerated parenchymal ACB permeability and decoupling OD and RD. Our data support the longstanding belief that R/D can cause injury. That said, the conditions under which healthy parenchyma would be subject to R/D, such that VILI might initiate with R/D, have yet to be identified. Further, whether OD ventilation with a higher peak pressure or for a longer period would be injurious remains to be determined. This abstract is funded by: NIH R56 HL113577
Battikha et al. (Fri,) studied this question.