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Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

ABSTRACT: Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.

SUBMITTER: Kazemi A

PROVIDER: S-EPMC6818804 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Kazemi Alireza A Louis Bruno B Isabey Daniel D Nieman Gary F GF Gatto Louis A LA Satalin Joshua J Baker Sarah S Grotberg James B JB Filoche Marcel M

PLoS computational biology 20191017 10

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by ...[more]

PMID: 31622332

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Project description:Atelectasis and surfactant depletion may contribute to greater distension-and thereby injury-of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes.Prospective imaging study in an animal model.Research imaging facility.Twenty-seven healthy Sprague Dawley rats.Surfactant depletion was obtained by saline lavage in anesthetized, ventilated rats. Alveolar recruitment was accomplished using positive end-expiratory pressure and exogenous surfactant administration.Airspace dimensions were estimated by measuring the apparent diffusion coefficient of He, using diffusion-weighted hyperpolarized gas magnetic resonance imaging. Atelectasis was demonstrated using computerized tomography and by measuring oxygenation. Saline lavage increased atelectasis (increase in nonaerated tissue from 1.2% to 13.8% of imaged area, p < 0.001), and produced a concomitant increase in mean apparent diffusion coefficient (~33%, p < 0.001) vs. baseline; the heterogeneity of the computerized tomography signal and the variance of apparent diffusion coefficient were also increased. Application of positive end-expiratory pressure and surfactant reduced the mean apparent diffusion coefficient (~23%, p < 0.001), and its variance, in parallel to alveolar recruitment (i.e., less computerized tomography densities and heterogeneity, increased oxygenation).Overdistension of aerated lung occurs during atelectasis is detectable using clinically relevant magnetic resonance imaging technology, and could be a key factor in the generation of lung injury during mechanical ventilation. Lung recruitment by higher positive end-expiratory pressure and surfactant administration reduces airspace distension.

Project description:BackgroundDeclined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Carbon nanoparticles (CNP) are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ) with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1) mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution.Methods5 ?g, 20 ?g and 50 ?g CNP (Printex 90) were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 ?g dosage). Inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.Results24 h after instillation, 20 ?g and 50 ?g CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN) respectively while the 5 ?g represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3), and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3) were significantly decreased at day 3 (72.9 × 10E3) and day 7 (48.5 × 10E3) but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3) and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3) compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation.ConclusionThis explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day 7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22/MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon.

Dataset Information

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Publications

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

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