A longitudinal characterization of cardiopulmonary and systemic injury following acute chlorine inhalation in rats.

Chlorine is a highly reactive, toxic industrial gas whose accidental or intentional release poses a significant public health threat, highlighting the need for effective medical countermeasures. Well-characterized animal models are essential for understanding the mechanisms of chlorine-induced injury and evaluating potential therapeutics. In this study, we established a longitudinal preclinical rat model of acute chlorine inhalation using two near lethal (LD50) exposures (500 or 600 ppm for 45 min) in unanesthetized adult Sprague Dawley rats. Pulmonary and systemic injury were evaluated at 3, 6 and 24 h postexposure using clinical, biochemical, hematological, physiological and histopathological endpoints. Both exposure concentrations produced approximately 50% mortality with most deaths occurring shortly after exposure, while survivors exhibited severe respiratory distress, increased clinical scores, weight loss, bradycardia and hypoxemia. Arterial blood gas analysis demonstrated impaired gas exchange characterized by hypercapnia and compensated respiratory acidosis. Chlorine exposure induced robust pulmonary inflammation and injury, evidenced by increased BALF protein, LDH and the damage associated molecular pattern (DAMP) HMGB1, pulmonary edema, airway epithelial sloughing, alveolar damage and elevated lung injury scores. Systemic inflammation was characterized by neutrophilia with concurrent lymphopenia and monocytopenia. Vascular injury was indicated by increased syndecan-1 concentrations in BALF and plasma while cardiac involvement was demonstrated by increased heart-to-body weight ratios, elevated circulating cardiac injury biomarkers and ultrastructural myocardial damage. Collectively, this well-characterized model recapitulates the major manifestations of acute chlorine toxicity and provides a robust platform for investigating disease mechanisms and evaluating candidate medical countermeasures.