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

OBJECTIVE

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.

MATERIALS AND

METHODS

Male swine (approximately 14 weeks old) were anesthetized, paralyzed, intubated, and exposed to clean air or Cl2 while connected to a ventilator. The exposed LD50/24 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.

RESULTS

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.

DISCUSSION/

CONCLUSIONS

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.