(A-19) The Perilous Effect of Concentrated Energy Dissipation during Acinar Recruitment

Introduction:: Acute respiratory distress syndrome (ARDS) is a critical condition characterized by pulmonary edema and hypoxemia. In the United States, ARDS affects approximately 190,000 individuals each year, with a high mortality rate of 38.5% [1]. The predominant approach for treating ARDS is supportive care, which mainly focuses on mechanical ventilation. However, the pathologic changes in alveolar mechanics that occur in ARDS render the lung susceptible to the development of secondary ventilator-induced lung injury (VILI). The primary mechanisms associated with VILI include overstretching of (volumtrauma) and high pressure (barotrauma) applied on lung units, as well as repeated closing and opening (Recruitment/De-recruitment, RD) of lung units (atelectrauma).

During atelectrauma, the repeated RD can generate microbubbles and interfacial flows, which can transmit mechanical forces to the airway lumen and cause cellular necrosis. Also, the heterogeneous inflation in the alveolar region may induce significant stress on the neighboring normal alveoli due to their adjacency to collapsed ones [2]. It is recognized that multiscale interactions exist that damage the sensitive tissues in the lung. The increased permeability due to the initial injury may cause surfactant deactivation and initiate a series of multiscale biophysical interactions hypothesized in the POOR (Permeability-Originated Obstructive Response)-Getting-POORer theory [3]. We construct a multiscale computational model to simulate mechanical ventilation and RD events in the alveolar regions. This model predicts the lung behaviors and functions under RD and investigates the energy dissipation associated to help elucidate the injury mechanism of VILI.

Materials and Methods:: This computational model follows our previous model with a heterogenous airway tree structure and multilayer surfactant-surface tension dynamics [4]. Mechanical ventilation modes are simulated by defining the pressure condition at the trachea opening. We simulate ARDS by introducing surfactant dysfunction and alveolar RD. We divide the original acini that would normally operate with stable internal alveolar responses into heterogenous sub-acinar Alveolar Clusters (sACs) that can become unstable due to ARDS (Figure 1A). Each sAC can either be open or closed, which is determined by the movement of a “virtual trajectory” [5]. Alveolar RD is simulated by considering the resistance and compliance changes that result in an altered pressure-volume relationship (Figure 1B).

Results, Conclusions, and Discussions:: The results from the computational simulations include 1. Predictions of heterogenous RD events. 2. Characteristic pressure-volume relationships with the opening and closing phases that resemble the measurements from animal experiments. 3. Estimation of the dissipated energy that could be damaging to the lung and contribute to VILI.

Energy dissipation due to RD is highly concentrated in space (locally at recruited sACs) and time (average recruitment time < 0.5s), which may damage the sensitive tissue and lead to VILI. Ventilation modes should be designed to minimize energy dissipation for protective treatment strategies.

Acknowledgements (Optional): : Funded by NIH R01HL142702 and NSF CBET 1706801

References (Optional): : [1] Matthay et al., (2019), Nat Rev Dis Primers.;5(1):18. [2] Ramcharran et al., (2022), J Appl Physiol., 133(5):1093-1105. [3] Gaver et al., (2020), Am J Respir Crit Care Med., 202(8):1081-1087. [4] Ma et al., (2020), Front Physiol., 14;11:941. [5] Massa et al., (2008), J Appl Physiol., 105(6): p. 1813-21.