Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats

Abstract

Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD) in a whole-body exposure chamber, and given oxygen (0.8 Fi) or air (0.21 Fi) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats

“…Of great interest, unanesthetized Br 2 -exposed rats have a significant decrease in heart rate within the first 24 h consistent with Cl 2 inhalation. This finding of bradycardia and respiratory depression in halogen exposure suggests a direct or indirect effect of halogen exposure on the brain regulatory centers and/or sympathetic ganglia, resulting in a reduced ventilatory drive, hypoventilation, and bradycardia (47). Indeed, cardiac ultrastructural damage is consistent with acute adrenergic discharge that, although not manifest acutely, certainly is evident at 7 days when there is unequivocal evidence of LV dilatation and LV systolic and diastolic dysfunction.…”

Development of chlorine-induced lung injury in the anesthetized, spontaneously breathing pig

“…Okponyia et al (2018) reported severe bradypnea in rats during, and following, whole body high dose chlorine exposure, where respiratory rate rapidly decreased. The authors attribute the changes seen in respiratory parameters, in part, to a direct response of the activation of TRP channels within the respiratory tract resulting in altered breathing pattern (Okponyia et al 2018). Based on the evidence presented, the immediate changes in breathing pattern seen during exposure in our studies could be the result of a combination of activation of nerve fibers, such as pulmonary C-fibers, in the airways causing reflex changes in respiratory parameters as well as activation of specific TRPA1 ion channels.…”

“…Activation may result in initiation of pain, respiratory depression, secretions, and other protective responses such as bronchoconstriction (Bessac and Jordt 2010). Okponyia et al (2018) reported severe bradypnea in rats during, and following, whole body high dose chlorine exposure, where respiratory rate rapidly decreased. The authors attribute the changes seen in respiratory parameters, in part, to a direct response of the activation of TRP channels within the respiratory tract resulting in altered breathing pattern (Okponyia et al 2018).…”

“…Similar changes were observed in anesthetized, ventilated sheep over a range of doses of chlorine; animals demonstrated rapid and sustained decreases in PaO 2 and PaO 2 /FiO 2 ratio, normal PaCO 2 levels and ventilation/perfusion mismatch (Batchinsky et al 2006;Fukuda et al 2016). Okponyia et al (2018) demonstrated an immediate and prolonged drop in peripheral oxygen saturation (SpO 2 ) over 6 h in rats exposed to a high dose of chlorine. The PaO 2 /FiO 2 ratio dropped to levels consistent with severe to extreme respiratory failure.…”

Chlorine Countermeasures: Supplemental Oxygen Equals Supplemental Lung Injury?

“…The work presented in this issue of the Journal by Okponyia and colleagues (pp. 107-116) was designed specifically to address that question (6).…”