Assessment of a Two-Hit Lung Injury Model: Spinal Cord Injury and Gastric Reflux

Spinal cord injuries, particularly those at the cervical level, pose a significant threat to respiratory health, with pulmonary complications like aspiration pneumonia standing as the most common cause of mortality in these individuals. Further, clinical data suggests that individuals with cervical-level spinal cord injuries have an elevated risk of experiencing acute lung injury and acute respiratory distress syndrome. We are developing a model which mimics aspiration associated with gastroesophageal reflux disease following spinal cord injury. Using a rat model of spinal cord injury, C2 hemisection (C2Hx), paired with intratracheal instillation of gastric juices, our aim is to understand how spinal cord injury makes the lung more susceptible to future injury, such that we can develop therapeutics to mitigate this post-spinal cord injury susceptibility. Acute lung injury models, such as bleomycin-induced injury, reveal altered respiratory patterning and neuroinflammation, reflecting the interplay between lung pathology and central nervous system responses. Similarly, spinal cord injury disrupts respiratory neural pathways and induces systemic inflammation. However, little is known about how a "two-hit" model of spinal cord injury and acute lung insult may jointly impact lung function, neural breathing control, and recovery of function. To test how this two-hit model may impact breathing and lung health, we assessed ventilation with whole body plethysmography and lung mechanics. Furthermore, to understand what led to these changes we assessed markers of inflammation in the brainstem and structural changes within the lungs. These assessments were performed in intact animals receiving phosphate-buffered saline, low dose gastric juice, or high dose gastric juice, and C2Hx animals receiving phosphate-buffered saline or low dose gastric juice. The two-hit model resulted in C2Hx animals showing an increase in lung resistance between phosphate-buffered saline and low dose gastric juice instillation groups, whereas intact animals showed no change in resistance regardless of instillation group. Plethysmography data in hypoxic-hypercapnia conditions also demonstrated a decrease in tidal volume in all groups post instillation regardless of injury status. The results of this project will provide valuable insight into how spinal cord injury might predispose individuals to lung injury and provide a model for developing therapeutic agents to mitigate lung injury in individuals with spinal cord injury. Craig H. Neilsen Foundation Post-Doctoral Fellowship (MDS), Kentucky Spinal Cord and Head Injury Research Trust (WJA) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.