Inhalation toxicology · 2024
Temporal evaluation of lung injury following chlorine Inhalation in a ventilated pig model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Neal Matthew, Harvilchuck Jill, Pressburger David, Coley William, Hu Tom C-C
Аннотация
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.
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.