Acute inflammatory response to contrast agent aspiration and its mechanisms in the rat lung

Abstract

Objectives/Hypothesis Contrast agent (CA) aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies. The underlying molecular biological mechanisms of acute response to CA aspiration in the respiratory organs remain unclear. The aims of this study were to elucidate the histological and biological influences of three kinds of CAs on the lung and to clarify the differences in acute responses. Study Design Animal model. Methods Eight‐week‐old male Sprague Dawley rats were divided into five groups (n = 6 in each group). Three groups underwent tracheal instillation of one of three different CAs: barium (Ba) sulfate, nonionic contrast agents (NICAs), and ionic contrast agents (ICAs). A control group was instilled with saline and a sham group was instilled with air. All animals were euthanized on day 2 after treatment and histological and gene analysis was performed. Results No animal died after CA or control/sham aspiration. Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs compared with the two other iodinated contrast agents. Increases in expressions of inflammatory cytokines (tumor necrosis factor [Tnf], interleukin‐1β [Il1b], and interferon‐γ [Ifng]) were observed in Ba aspiration rats, and upregulation of Il1b was seen in ICA aspiration rats. NICA did not cause obvious histologic changes or expressions of inflammatory cytokines and fibrosis‐related genes in the lungs. Conclusions Ba caused significantly more acute lung inflammation in a rodent model than did ioinic and nonionic iodinated CAs. Nonionic contrast did not cause any discernible inflammatory response in the lungs, suggesting that it may be the safest contrast for videofluoroscopic swallow studies. Level of Evidence NA Laryngoscope, 129:1533–1538, 2019

Chronic inflammatory response in the rat lung to commonly used contrast agents for videofluoroscopy

“…Aspiration of saline, ICA, and NICA did not cause any pathological pulmonary changes and immunological responses in the chronic phase. The high‐osmolality of ICA has been associated with pulmonary congestion in the acute stage, and pulmonary congestion and edema after ICA aspiration are improved within a few days after aspiration . In the chronic stage, it is reported that the reactions to ICA aspiration considerably decreased by the 42nd day, and a similar result was obtained in this study.…”

“…In group 3, Ba particles stayed in alveolar cavities and induced prolonged pathological changes in the lung such as thickened bronchiolar and alveolar walls, and granulation of the alveoli even on day 30 after tracheal administration of Ba suspension. However, these Ba particles were not phagocytosed by many inflammatory cells comparing with those at the acute stage of the previous study . In contrast, saline, ICA, and NICA did not cause pathologic changes in the lung.…”

“…In Ba‐treated rats, chronic findings such as thickened bronchiolar and alveolar walls, granulation formation in the alveoli, mild infiltration of CD3 + lymphocytes, and significant increase of Tnf expression were recognized on day 30 after aspiration, but the expression levels of other inflammatory cytokines ( Il1b , Il6 , Ifng ) did not show significant changes. Considering these results, immunological responses that identified insoluble Ba particles as foreign in the acute stage may weaken with time.…”

“…Radiographic contrast agents (CAs) are essential in VFSS and upper gastrointestinal studies. Barium sulfate (Ba), ionic iodinated contrast agent (ICA: diatrizoic acid), and nonionic iodinated contrast agent (NICAs: iohexol, iodixanol) are the most common agents currently used for VFSS and upper gastrointestinal investigations …”

“…Barium sulfate (Ba), ionic iodinated contrast agent (ICA: diatrizoic acid), and nonionic iodinated contrast agent (NICAs: iohexol, iodixanol) are the most common agents currently used for VFSS and upper gastrointestinal investigations. 3 CA aspiration is a well-known complication and presents a risk of increased morbidity and mortality. 4,5 The consequence of CA aspiration must be considered, because these studies are frequently performed on people with risk of aspiration.…”