DEVELOPMENT OF AN INHALATION MODEL FOR STUDYING HYDROGEN SULFIDE EXPOSURES

Abstract

SESSION TITLE: Obstructive Lung Disease/Toxic Inhalation SESSION TYPE: Original Investigations PRESENTED ON: 10/07/2018 02:15 PM - 03:15 PM PURPOSE: Hydrogen sulfide (H2S) is a toxic and potent gas, and human exposures occur frequently in nature and many industries; moreover, hydrogen sulfide inhalation can be used as a weapon of mass destruction and can be a major chemical threat to military personnel. H2S has been reported to cause direct pulmonary toxicity when inhaled. There is no current effective antidote for H2S, and understanding the underlying pathophysiology is a first step to identifying a potential antidote. Antidotes that can be given rapidly in a small volume and at a delayed time after sulfide exposure are a priority. To come up with an effective treatment, having a carefully controlled model, which can simulate a realistic scenario of toxic inhalation exposure as would likely be experienced by victims is essential. METHODS: A custom gas inhalation circuit was designed to deliver isoflurane anesthesia and hydrogen sulfide in a compressed air flow-by mixture to intubated New Zealand White rabbits. Compressed air was supplied to an Ohmeda VMC anesthesia machine, which vaporized isoflurane. The H2S gas was produced by dripping a 320mM NaHS solution at a rate of 2.5ml/min into a reaction vessel containing 150 ml 3N HCl. The H2S, air and isoflurane mixture then exited the reaction vessel and was delivered to the animal subject for inhalation thru a disposable respiratory non-rebreathing valve. The respiratory circuit, reaction vessel and animal subject were located within a fume hood, and the exhaled gas was sent to an activated charcoal filter (f/air) where the isoflurane and H2S were absorbed. H2S gas levels were monitored within the hood and circuit during the experiments. The in situ generation system enables high dose exposures without requiring a large tank of dangerous lethal gas present.Rabbit vital signs and physiological measures, including SPO2, heart rate, blood pressure, and minute ventilation were monitored and recorded throughout the experiment. Fatal exposure was defined as apnea accompanied by a decrease in blood pressure to a systolic value less than 20mmHg, at which point animals were euthanized. RESULTS: Rabbits experienced the first apnea episode within 5 minutes of H2S exposure. Heart rate initially decreased, and was accompanied by a decrease in blood pressure from a baseline mean arterial pressure of 52mmHg to less than 20mmHg systolic. The total volume of inhaled gas in this control group (n=6) averaged 7.35L. Average survival time was 10.5 minutes CONCLUSIONS: Death from H2S exposure occurs within minutes. Our preliminary studies have showed our ability to develop a stable, reproducible inhaled H2S toxic rabbit model; which will help us detect the outcomes of H2S toxicity, monitor response to treatments with various experimental potential antidote agents, and ultimately develop a specific antidote for this highly lethal gas. CLINICAL IMPLICATIONS: simulating H2S inhalation exposure to develop an antidote DISCLOSURES: No relevant relationships by vikhyat bebarta, source=Web Response No relevant relationships by Gerry Boss, source=Web Response No relevant relationships by Matthew Brenner, source=Admin input No relevant relationships by Tanya Burney, source=Web Response No relevant relationships by Jangwoen Lee, source=Web Response No relevant relationships by Sari Mahon, source=Web Response No relevant relationships by David Mukai, source=Web Response No relevant relationships by Tina Saber, source=Web Response No relevant relationships by Mayer Saidian, source=Web Response