Temporal evaluation of lung injury following chlorine Inhalation in a ventilated pig model

Chlorine (Cl₂) is a widely used industrial chemical and toxic human exposures have occurred from Cl₂ releases. No approved medical countermeasures (MCMs) exist for Cl₂-induced lung injuries. The objective of this study was to develop and characterize swine Cl₂ inhalation injuries to understand lung injury and histopathological sequalae.

Male swine (approximately 14 weeks old) were anesthetized, paralyzed, intubated, and exposed to clean air or Cl₂ while connected to a ventilator. The exposed LD_50/24 hr of 1.8 mg/kg was delivered within a 15-20-minute timeframe. Scheduled terminal timepoints were 6 h, 7- and 30-days post-exposure.

Following Cl₂ exposure, 46% of the animals succumbed with an average time to death of 1.42 h. Dynamic lung compliance at 6 h post-exposure was reduced 45%. Clinical observations demonstrated respiratory abnormalities similar to Cl₂ exposed humans. Compared to air shams, Cl₂-exposed animals had decreased SpO₂, arterial blood pH, pO₂, sO₂, increased blood lactate levels and deoxyhemoglobin levels at early timepoints. Increased neutrophils 6 h post- exposure occurred concurrent with increased inflammatory cytokines, bronchiolar epithelial necrosis with alveolar edema, cellular infiltrates, and lobular atelectasis.

Potentially relevant biomarkers involved in the progression and recovery from acute Cl₂ lung injury in this model include lung compliance, select cytokines/chemokines, arterial blood gas parameters, and histopathological evaluation. Normal lung histopathological observations beyond 7- days indicates that histopathological evaluations should occur earlier. This animal model delivers accurate and consistent Cl₂ exposures resulting in a human-relevant lung injury for evaluating MCM efficacy against Cl₂-mediated acute lung injury.