title: Differential sensitivity of lung and brain to sulfide exposure: a peripheral mechanism for apnea.
abstract: Acute exposure to hydrogen sulfide (H2S) causes 4 dose-dependent responses: hyperpnea, unconsciousness or knockdown, apnea, and death. At present, scientific mechanisms for these effects are unknown, but inhibition of cytochrome oxidase in the central nervous system (CNS) by sulfide has been suggested. In this study, the premise of brain as target is examined by comparing peripheral with direct delivery of sulfide to brain. NaHS was administered to anesthetized Sprague-Dawley male rats, by femoral intravenous, or carotid intra-arterial injection. With apnea as the test, ED100 values of 0.6 and 3.0 mg kg(-1) were found for peripheral and direct delivery to brain, respectively. Peripheral delivery is 5 times as effective as direct delivery to the brain, and greater if the relative dilution factors are considered. Lidocaine, applied to the vagus, prevented apnea, so lung-brain transmission was essential. It was therefore concluded that the lung is the peripheral site of action. Hyperpnea increased in duration with dose. The carotid body, located distal to the arterial catheter, sensed the high doses of NaHS but did not trigger apnea. Intravenous infusion or intraperitoneal injection with NaHCO3 prevented hyperpnea, apnea, and death. The following conclusions are drawn: the carotid body is not implicated in NaHS-induced apnea, the lung and not brain harbors the primary site of action of H2S, and an afferent neural signal from the lung via the vagus induces the apnea. Finally, NaHCO3 appears to prevent toxicity from sulfide, and therefore H2S, by some unexplained mechanism. Practical emergency treatment for acute toxicity in the field may be possible.
authors.affiliation: Department of Public Health Sciences, Faculty of Medicine and Oral Health Sciences, University of Alberta, Edmonton, Canada.
authors.forename: A F
authors.initials: AF
authors.lastname: Almeida
authors.forename: T L
authors.initials: TL
authors.lastname: Guidotti
mesh_terms: D000758:Anesthesia; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001049:Apnea / Q000139:chemically induced*; D001639:Bicarbonates / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002339:Carotid Arteries; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008012:Lidocaine / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012501:Saphenous Vein; D013440:Sulfides / Q000633:toxicity*
chemical_list: D000779:Anesthetics, Local; D001639:Bicarbonates; D013440:Sulfides; D008012:Lidocaine; C033479:sodium sulfide