Acute Chlorine Research Articles

Quantitative assessment of chlorine gas inhalation injury based on endoscopic OCT and spectral encoded interferometric microscope imaging with deep learning.

Chlorine exposure can cause severe airway injuries. While the acute effects of chlorine inhalation are well-documented, the structural changes resulting from the post-acute, high-level chlorine exposure remain less understood. Airway sloughing is one of the standards for doctors to evaluate the lung function. Here, we report the application of a high-resolution swept-source optical coherence tomography system to investigate the progression of injury based on airway sloughing evaluation in a chlorine inhalation rabbit model. This system employs a 1.2mm diameter flexible fiberoptic endoscopic probe via an endotracheal tube to capture in vivo large airway anatomical changes before and as early as 30minafter acute chlorine exposure. We conducted an animal study using New Zealand white rabbits exposed to acute chlorine gas (800 ppm, 6min) during ventilation and monitored them using optical coherence tomography (OCT) for 6h. To measure the volume of airway sloughing induced by chlorine gas, we utilized deep learning for the segmentation task on OCT images. The results showed that the volume of chlorine induced epithelial sloughing on rabbit tracheal walls initially increased, peaked around 30min, and then decreased. Furthermore, we utilized a spectral encoded interferometric microscopy system to study ex vivo airway cilia beating dynamics based on Doppler shift, aiding in elucidating how chlorine gas affects cilia beating function. Cilia movability and beating frequency were decreased because of the epithelium damage. This quantitative approach has the potential to enhance the diagnosis and monitoring of injuries from toxic gas inhalation and to evaluate the efficacy of antidote treatments for these injuries.

Chlorine-Induced Toxicity on Murine Cornea: Exploring the Potential Therapeutic Role of Antioxidants.

Chlorine (Cl2) exposure poses a significant risk to ocular health, with the cornea being particularly susceptible to its corrosive effects. Antioxidants, known for their ability to neutralize reactive oxygen species (ROS) and alleviate oxidative stress, were explored as potential therapeutic agents to counteract chlorine-induced damage. In vitro experiments using human corneal epithelial cells showed decreased cell viability by chlorine-induced ROS production, which was reversed by antioxidant incubation. The mitochondrial membrane potential decreased due to both low and high doses of Cl2 exposure; however, it was recovered through antioxidants. The wound scratch assay showed that antioxidants mitigated impaired wound healing after Cl2 exposure. In vivo and ex vivo, after Cl2 exposure, increased corneal fluorescein staining indicates damaged corneal epithelial and stromal layers of mice cornea. Likewise, Cl2 exposure in human ex vivo corneas led to corneal injury characterized by epithelial fluorescein staining and epithelial erosion. However, antioxidants protected Cl2-induced damage. These results highlight the effects of Cl2 on corneal cells using in vitro, ex vivo, and in vivo models while also underscoring the potential of antioxidants, such as vitamin A, vitamin C, resveratrol, and melatonin, as protective agents against acute chlorine toxicity-induced corneal injury. Further investigation is needed to confirm the antioxidants' capacity to alleviate oxidative stress and enhance the corneal healing process.

Establishing Population Values for Chlorine Exposure in the United States (2015-2016) Using 2 Chlorine Biomarkers, 3-Chlorotyrosine and 3,5-Dichlorotyrosine.

In the United States, 12 million short tons of chlorine are manufactured and transported each year. Due to the volume of this volatile chemical, large- and small-scale chemical exposures occur frequently. To diagnose and treat potentially exposed individuals, reference range values for confirmatory biomarkers are required to differentiate between normal and abnormal exposure levels. Serum surplus samples (n = 1780) from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 were measured for 2 chlorine biomarkers, 3-chlorotyrosine (Cl-Tyr) and 3,5-dichlorotyrosine (Cl2-Tyr), by liquid chromatography coupled to a triple quadrupole mass spectrometer. We evaluated demographic factors associated with elevated biomarker levels. Participant samples were analyzed for the chlorine biomarkers Cl-Tyr and Cl2-Tyr. In the unweighted analysis of these samples, 1349 (75.8%) were under the limit of detection (< LOD) of 2.50 ng/mL for Cl-Tyr and 1773 (99.6%) were < LOD for Cl2-Tyr. Samples within the method reportable range were 2.50 to 35.6 ng/mL for Cl-Tyr and 2.69 to 11.2 ng/mL for Cl2-Tyr. Since only 7 of the 1780 participants had detectable Cl2-Tyr, statistical analysis was limited to Cl-Tyr. Of the demographic characteristics examined, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), and sex exhibited statistically significant differences in the weighted prevalence of detectable Cl-Tyr. This is the first reported set of Cl-Tyr and Cl2-Tyr population values for the United States. This population range coupled with NHANES demographic information could help healthcare professionals distinguish between normal and abnormal chlorine biomarker levels in an emergency. With this information, an inference could be made when determining acute chlorine exposure in individuals.

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication

An unexpected side effect of the pesticide ban: Acute chlorine poisoning rates are rising

An unexpected side effect of the pesticide ban: Acute chlorine poisoning rates are rising

Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem

Introduction: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. Methods: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. Results: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0–1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. Conclusion: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.

Chlorine gas hazardous material incident in Karachi, Pakistan: A clinical experience from an emergency department of a tertiary care hospital.

To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. There were 51 male patients with a mean age of 33.10±8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p>0.05). Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications were rare and there was no mortality.

Clinical Features and Outcomes of Acute Chlorine Gas Inhalation; a Brief Report.

Introduction:On March 6th,2020, chlorine gas leak was reported at Engro Polymer & Chemicals Plant in Karachi City, Pakistan. This study aimed to evaluate the clinical features and outcomes of patients who presented to emergency department (ED) following this event.Methods:This retrospective cross-sectional study, evaluated the clinical features and outcomes (length of hospital stay, complications, and mechanical ventilation requirement) of patients presenting to ED of Aga Khan University Hospital, Karachi, Pakistan, with history of chlorine gas exposure at the Engro Plant from 6th March to 14th March 2020. Results:38 patients with mean age of 33.1 ± 8.1 years presented to ED with history of chlorine gas exposure (100% male). 4 (10.5%) cases had comorbid diseases. Most common presenting symptom was dyspnea, observed in 33 (86.8%) cases, followed by cough, seen in 27 (71.1%) subjects. 13.2% (5/38) patients had infiltration on chest x-ray and 33 (86.8 %) required hospitalization. 6 (15.8%) patients had repeat presentation requiring hospitalization or ED visit. 18 (47.4%) were managed with high flow oxygen therapy, 9 (23.7%) required non-invasive ventilation and one patient was intubated due to development of pneumo-mediastinum. Mean length of stay was 1.55 ± 1.58 days and no patients died. Presence of tachycardia was the only finding significantly associated with need for oxygen (p = 0.033) and non-invasive ventilation (p = 0.012).Conclusion:The majority of patients presenting with acute chlorine gas exposure showed good clinical outcomes and rapid recovery, however, a high index of suspicion and vigilance should be maintained for complications such as pneumomediastinum and acute respiratory distress syndrome in these patients.

Clinical analysis of 6 critically ill children with acute chlorine poisoning

Objective: To analyze the clinical characteristics and treatment of critically ill children with acute chlorine poisoning and explore the risk factors and effective strategies. Methods: This retrospective study collected the clinical data, including general state, clinical characteristics, treatment and follow-up(till 1 year and 6 months after discharge), of 6 critically ill children who were hospitalized in the Pediatric Intensive Care Unit of Beijing Children's Hospital due to acute chlorine poisoning in August 2019. Results: There were 6 children characterized by severe dyspnea in this accident, among whom 4 were boys and two girls, aged 4-12 years. When the accident occurred, they were within 5 m of the chlorine source. These patients underwent tracheal intubation and mechanical ventilation in 3.5-7.0 h after poisoning. The child who was the closest to the chlorine source (1.5 m) and took the longest time (5 min) to evacuate was the most severe one. He suffered hypoxia which could not be corrected by conventional mechanical ventilation and severe shock, then had veno-arterial extracorporeal membrane oxygenation(ECMO) treatment started 10 h after the accident. All the 6 children in this study survived. Following-up found no growth and developmental abnormality. The pulmonary function tests were normal except for one case with increased small airway resistance due to previous suspected asthma, and the lung CT, electhoencephalogram, and brain magnetic resonance imaging were all normal. Conclusions: Severe chlorine poisoning is mainly characterized by respiratory failure. Mechanical ventilation is often required within a few hours after poisoning. When conventional mechanical ventilation is ineffective, ECMO could save live. Timely treatment could improve prognosis.

Acute chlorine poisoning caused by an accident at a swimming pool

Chlorine is an irritant gas that is widely used in water purification. Several previous reports had reported accidents of inhalation injuries at swimming pools. However, there have been limited data on the detection of on-site chlorine concentration. This study aims to report a chlorine leakage accident at a swimming pool caused by improper disinfection operations. Calculation using the gas diffusion simulation software showed that the on-site chlorine concentration was 221.45 ppm. When the accident occurred, there were 92 individuals at the swimming pool and the gym, among which 61 were referred to the emergency department of five different hospitals for feeling ill. Among them, 22 patients underwent chest high-resolution computed tomography scans in our hospital. According to the findings, 4 (18.2%) patients had peribronchitis, 3 (13.6%) had tracheobronchitis, 4 (18.2%) had pneumonia, 4 (18.2%) had interstitial pulmonary edema, and 3 (13.6%) had alveolar pulmonary edema. The symptoms of 22 patients who visited our hospital significantly improved after comprehensive treatment. Three months after the accident, 8 of 17 patients presented obstructive ventilation defects or small airway dysfunction. The accidental exposure to chlorine may induce acute poisoning with various respiratory injuries and prolonged lung dysfunction.

Toxic Myocardial Injury in a Patient With Coronary Atherosclerosis, Caused by Acute Poisoning With Gaseous Chlorine

Acute chlorine gas poisoning leads to activation of the sympathetic nervous system and, as a consequence, dysfunction of the cardiovascular system (CVS). We report a clinical case of toxic myocardial injury with gaseous chlorine. In a man with coronary artery disease and polypathy, toxic myocardial injury mimicked acute coronary syndrome (ACS) and was accompanied by a large area of left ventricular microvascular dysfunction, which did not coincide with the areas of blood supply of altered coronary arteries; the dynamics of electrocardiographic changes resembled myocardial stunning in Takotsubo syndrome (TS). The effect of chlorine on CVS, features of clinical and instrumental diagnostics and differentiation of primary / secondary CT and ACS are discussed.

Development of a clinical assay to measure chlorinated tyrosine in hair and tissue samples using a mouse chlorine inhalation exposure model.

Chlorine is a toxic industrial chemical with a history of use as a chemical weapon. Chlorine is also produced, stored, and transported in bulk making it a high-priority pulmonary threat in the USA. Due to the high reactivity of chlorine, few biomarkers exist to identify exposure in clinical and environmental samples. Our laboratory evaluates acute chlorine exposure in clinical samples by measuring 3-chlorotyrosine (Cl-Tyr) and 3,5-dichlorotyrosine (Cl2-Tyr) using liquid chromatography tandem mass spectrometry (LC-MS/MS). Individuals can have elevated biomarker levels due to their environment and chronic health conditions, but levels are significantly lower in individuals exposed to chlorine. Historically these biomarkers have been evaluated in serum, plasma, blood, and bronchoalveolar lavage (BAL) fluid. We report the expansion into hair and lung tissue samples using our newly developed tissue homogenization protocol which fits seamlessly with our current chlorinated tyrosine quantitative assay. Furthermore, we have updated the chlorinated tyrosine assay to improve throughput and ruggedness and reduce sample volume requirements. The improved assay was used to measure chlorinated tyrosine levels in 198 mice exposed to either chlorine gas or air. From this animal study, we compared Cl-Tyr and Cl2-Tyr levels among three matrices (i.e., lung, hair, and blood) and found that hair had the most abundant chlorine exposure biomarkers. Furthermore, we captured the first timeline of each analyte in the lung, hair, and blood samples. In mice exposed to chlorine gas, both Cl-Tyr and Cl2-Tyr were present in blood and lung samples up to 24h and up to 30days in hair samples.

Clinical Presentations and Outcomes of Industrial Chlorine Gas Exposure Incidence in Oman.

The main objective was to study different clinical presentations and outcomes of patients after acute industrial chlorine gas exposure in Oman with evaluation of overall incident management to help develop a chemical exposure incident protocol. This was a retrospective observational study of 15 patients exposed to chlorine gas after an accidental chlorine gas leak in a metal melting factory in Oman. Six (40%) patients were admitted and nine (60%) patients were discharged from the emergency department (ED) after initial management. The important post-chlorine gas exposure clinical symptoms were eye irritation (66.6%), cough (73.3%), shortness of breath (40.0%), chest discomfort (66.6%), rhinorrhea (66.6%), dizziness (40.0%), vomiting (46.6%), sore throat (13.3%), and stridor (53.3%). Important signs included tachycardia (40.0%), tachypnea (40.0%), wheeze (20.0%), and use of accessory muscles for breathing (20.0%). Signs and symptoms of eye irritation, rhinorrhea, tachycardia, tachypnea, wheeze, and use of accessory muscles for breathing have shown significant correlation with outcome (admission) having P value of <.05. In the presented acute chlorine gas exposure incidence, 15 exposed persons were brought to the ED, out of which six were admitted and nine were discharged after symptomatic treatment. Signs and symptoms of eye irritation, rhinorrhea, tachycardia, tachypnea, wheeze, and use of accessory muscles of breathing show significant relation with the outcome of admission.

Chlorine intoxication as a medical problem

This article deals with problems of pathogenesis, clinical symptomatology, approaches to detection and treatment of acute and chronic chlorine intoxication.

Low dose of chlorine exposure exacerbates nasal and pulmonary allergic inflammation in mice

Work-exacerbated asthma (WEA) is defined as preexisting asthma that worsens with exposure to irritants [e.g., chlorine (Cl2) derivatives] in the workplace. The maximum allowable concentration in the workplace of Cl2 exposure is 3 mg/ m3 (described in OSHA). We investigated in an experimental asthma model in mice the effects of a single exposure to a sodium hypochlorite dose with this allowed chlorine concentration and a tenfold higher dose. Acute chlorine exposure at 3.3 mg/m3 in the OVA-sensitized group increased eosinophils in the peribronquial infiltrate, cytokine production, nasal mucus production and the number of iNOS positive cells in the distal lung compared to only sensitized mice. The exposure to a higher dose of 33.3 mg/m3 in the OVA-sensitized group resulted in an increase in respiratory system elastance, in the total and differential numbers of inflammatory cells in bronchoalveolar lavage fluid, IL-4, IL-5, and IL-17 in the lungs, eosinophils in peribronquial infiltrate and mucus content in nasal compared to non-exposed and sensitized animals. In this asthma model, chorine exposures at an allowable dose, contributed to the potentiation of Th2 responses. The functional alterations were associated with increased iNOS and ROCK-2 activation in the distal lung.

Halogen Inhalation-Induced Lung Injury and Acute Respiratory Distress Syndrome.

Objective:Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.Data Sources:This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: “chlorine,” “bromine,” “lung injury,” and “ARDS.”Study Selection:The original articles and reviews including the topics were the primary references.Results:Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.Conclusions:At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24h after exposure to 800ppm chlorine for 4min to study acute effects or up to 7days after exposure to 400ppm for 8min to study longer term effects. Acute effects observed 6 or 24h after inhalation of 800ppm chlorine for 4min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400ppm chlorine for 8min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury.

A Case Report: What is the Real Cause of Death from Acute Chlorine Exposure in an Asthmatic Patient?

A Case Report: What is the Real Cause of Death from Acute Chlorine Exposure in an Asthmatic Patient?

Dietary effects on immunity, stress, and efficacy of two live attenuated Flavobacterium psychrophilum vaccine formulations

The effects of feeding a commercially available health enhancing aquaculture feed (Bio-Oregon's BioPro/Protec® diet) on the efficacy of two coldwater disease (CWD) vaccine formulations consisting of Flavobacterium psychrophilum 259-93B.17 (B.17) and B.17 grown in iron limited medium (ILM) were carried out in two separate trials. The primary aim of this study was to compare efficacy of the B.17 and ILM formulations in rainbow trout (Oncorhynchus mykiss). A secondary aim was to determine if dietary alterations could enhance the immune response and/or elicit greater levels of protection. Therefore, a basal diet (BioOlympic fry diet; control feed) and an immunostimulatory diet (BioPro; IS feed) were fed to rainbow trout at 2% body weight (bwt) per day for 2weeks prior to immersion immunization with the B.17 vaccine, ILM vaccine, or a TYES media control. A booster immunization was administered two weeks post initial vaccination, and feeding of the respective feeds continued for one additional week at which time all groups received the control diet until the end of the experiment. In trial 1, an acute chlorine spike occurred just prior to pathogen challenge (week 7) resulting in substantial mortality among treatment groups. Interestingly, fish fed the IS feed had significantly lower mortality (36.7%) than fish fed the control feed (67%). Vaccinated fish had significantly higher antibody titers than the control fish at week 2 through 7 in trial 1. In trial 2, antibody titers for all vaccinated fish were significantly greater than controls at week 4, but at weeks 6 and 8 the titers of B.17 vaccinated fish were not significantly different from controls. However, average titers for ILM vaccinated were significantly greater than control fish at weeks 6 and 8. Cumulative percent mortality (CPM) in B.17 and ILM vaccinated groups was significantly lower than control groups at the point where CPM reached 60% (mid-way through outbreak), but by the end of the challenge (28days) ILM vaccinated fish had significantly lower CPM than either control or B.17 vaccinated fish. When comparing dietary effects, CPM was not significantly different but RPS values for fish fed the BioPro IS feed were consistently elevated over groups fed the control diet regardless of the vaccine formulation administered. This study demonstrates increased efficacy of the ILM vaccine in rainbow trout, and provides evidence that a commercial “health enhancing” diet can provide benefits in response to an acute stress event and may contribute to increased vaccine performance. Statement of relevanceThis manuscript addresses an important and very practical problem in aquaculture. Coldwater disease is a major disease affecting salmonid aquaculture around the world. There is no approved vaccine available in the US. This manuscript reports the beneficial effects of feeding commercial immunostimulatory functional feeds on the efficacy of two formulations of a coldwater disease vaccine. The results presented here are highly relevant to the development of aquaculture and finding sustainable and non-antibiotic based aquatic animal health management strategies. This study will contribute towards coldwater disease management and identifies potential benefits of commercial functional feeds commonly used in the aquaculture industry.

Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity.

Autopsy specimens from human victims or experimental animals that die due to acute chlorine gas exposure present features of cardiovascular pathology. We demonstrate acute chlorine inhalation-induced reduction in heart rate and oxygen saturation in rats. Chlorine inhalation elevated chlorine reactants, such as chlorotyrosine and chloramine, in blood plasma. Using heart tissue and primary cardiomyocytes, we demonstrated that acute high-concentration chlorine exposure in vivo (500 ppm for 30 min) caused decreased total ATP content and loss of sarcoendoplasmic reticulum calcium ATPase (SERCA) activity. Loss of SERCA activity was attributed to chlorination of tyrosine residues and oxidation of an important cysteine residue, cysteine-674, in SERCA, as demonstrated by immunoblots and mass spectrometry. Using cardiomyocytes, we found that chlorine-induced cell death and damage to SERCA could be decreased by thiocyanate, an important biological antioxidant, and by genetic SERCA2 overexpression. We also investigated a U.S. Food and Drug Administration-approved drug, ranolazine, used in treatment of cardiac diseases, and previously shown to stabilize SERCA in animal models of ischemia-reperfusion. Pretreatment with ranolazine or istaroxime, another SERCA activator, prevented chlorine-induced cardiomyocyte death. Further investigation of responsible mechanisms showed that ranolazine- and istaroxime-treated cells preserved mitochondrial membrane potential and ATP after chlorine exposure. Thus, these studies demonstrate a novel critical target for chlorine in the heart and identify potentially useful therapies to mitigate toxicity of acute chlorine exposure.