Research Article: Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats

Date Published: June 4, 2018

Publisher: Public Library of Science

Author(s): Florian Setzer, Barbara Schmidt, Lars Hueter, Konrad Schwarzkopf, Jörg Sänger, Torsten Schreiber, Michael Koval.


Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue.

Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion.

Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4–24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung.

These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

Partial Text

Aspiration of gastric acid, potentially resulting in pneumonitis, is an important cause of acute lung injury and respiratory failure [1, 2] and a potential complication of clinical conditions associated with impaired consciousness due to a variety of reasons, including general anesthesia [3–5].

This study was approved by the institutional and local Animal Protection Committee (Thüringer Landesamt für Lebensmittelsicherheit und Verbraucherschutz, Bad Langensalza, Germany; 02-27/04 and 02-011/06). Male Wistar rats from an in-house outbred strain, 10–12 weeks old, weighing 381 (±2) g were used. Rats were housed in the animal facility of the university under standard conditions, at constant temperature (21°C) and a regular day-night cycle with food and water ad libitum. Animals were handled according to the institutional guidelines for the care of laboratory animals and the laws of the state of Thuringia, Germany. Invasive procedures were performed under anesthesia with isoflurane as described below. Experiments were carried out on weekdays, in the designated laboratories of the university. Rats were observed and examined daily during the longitudinal experiments. (S1 Text)

Acid instillation caused transient symptoms of illness in varying degree (slightly reduced locomotion, piloerection, and occasionally, tachypnea) for 4–6 hours. Symptoms were mild and resolved spontaneously in all animals. No deaths occurred. Effects of acid instillation were visible as consolidated areas extending to approximately 50% of the surface of deflated left lungs at 4 and 24 h and to approximately 20–30% of the left lung surface at 48 and 96 h after acid instillation. Residual alterations on left lungs were visible in 5 animals at 168 hours. Left lungs of the other 9 animals in this group appeared normal and comparable to the lungs of non-acid instilled animals. Macroscopically, bilateral lung injury was present in 1 animal in the 24 hours group and right lung injury was present in 1 animal in the 48 hours group. Both animals were excluded from data analysis.

This study comprehensively characterizes, in a zero-mortality animal model, the response to unilateral lung acid aspiration in both directly injured and non-injured lung areas.

This study demonstrates that after unilateral lung acid injury a bilateral pulmonary response is present for approximately 96 hours including profound inflammation and detrimental functional effects in directly damaged and mild to moderate inflammatory effects in not directly injured lung.




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