title: H2S concentrations in the arterial blood during H2S administration in relation to its toxicity and effects on breathing.
abstract: Our aim was to establish in spontaneously breathing urethane-anesthetized rats, the relationship between the concentrations of H2S transported in the blood and the corresponding clinical manifestations, i.e., breathing stimulation and inhibition, during and following infusion of NaHS at increasing rates. The gaseous concentration of H2S (CgH2S, one-third of the total soluble form) was computed from the continuous determination of H2S partial pressure in the alveolar gas, while H2S, both dissolved and combined to hemoglobin, was measured at specific time points by sulfide complexation with monobromobimane (CMBBH2S). We found that using a potent reducing agent in vitro, H2S added to the whole blood had little interaction with the plasma proteins, as sulfide appeared to be primarily combined and then oxidized by hemoglobin. In vivo, H2S was undetectable in the blood in its soluble form in baseline conditions, while CMBBH2S averaged 0.7 ± 0.5 μM. During NaHS infusion, H2S was primarily present in nonsoluble form in the arterial blood: CMBBH2S was about 50 times higher than CgH2S at the lowest levels of exposure and 5 or 6 times at the levels wherein fatal apnea occurred. CgH2S averaged only 1.1 ± 0.7 μM when breathing increased, corresponding to a CMBBH2S of 11.1 ± 5.4 μM. Apnea occurred at CgH2S above 5.1 μM and CMBBH2S above 25.4 μM. At the cessation of exposure, CMBBH2S remained elevated, at about 3 times above baseline for at least 15 min. These data provide a frame of reference for studying the putative effects of endogenous H2S and for testing antidotes against its deadly effects.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Penn State University College of Medicine, Hershey, Pennsylvania; and.
authors.forename: Candice M
authors.initials: CM
authors.lastname: Klingerman
authors.forename: Neil
authors.initials: N
authors.lastname: Trushin
authors.forename: Bogdan
authors.initials: B
authors.lastname: Prokopczyk
authors.forename: Philippe
authors.initials: P
authors.lastname: Haouzi
mesh_terms: D000818:Animals; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000097:blood* / Q000633:toxicity*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology*
chemical_list: D006862:Hydrogen Sulfide
keywords: control of respiration; hydrogen sulfide; toxicity
references.citation: Antioxid Redox Signal. 2012 Jul 1;17(1):11-21
references.pmid: 22221071
references.citation: Sci Signal. 2009 Nov 10;2(96):ra72
references.pmid: 19903941
references.citation: Toxicol Appl Pharmacol. 1990 May;103(3):482-90
references.pmid: 2160136
references.citation: Toxicol Appl Pharmacol. 1966 Jan;8(1):159-72
references.pmid: 5921892
references.citation: Annu Rev Pharmacol Toxicol. 1992;32:109-34
references.pmid: 1605565
references.citation: J Occup Med. 1985 May;27(5):373-6
references.pmid: 3159860
references.citation: Vet Hum Toxicol. 1997 Jun;39(3):152-4
references.pmid: 9167244
references.citation: West J Emerg Med. 2011 Jul;12(3):300-4
references.pmid: 21731786
references.citation: Biochim Biophys Acta. 1958 Jun;28(3):573-8
references.pmid: 13560409
references.citation: J Appl Physiol (1985). 1995 Feb;78(2):433-40
references.pmid: 7759410
references.citation: Crit Care. 2012 Oct 02;16(5):R178
references.pmid: 23031430
references.citation: Int J Toxicol. 2008;27(3):287-93
references.pmid: 18569170
references.citation: Crit Rev Toxicol. 1984;13(1):25-97
references.pmid: 6378532
references.citation: Arch Environ Health. 1976 May-Jun;31(3):166-9
references.pmid: 1275562
references.citation: Respir Physiol Neurobiol. 2013 Mar 1;186(1):87-94
references.pmid: 23333818
references.citation: Toxicology. 2007 Dec 5;242(1-3):16-22
references.pmid: 17976885
references.citation: Biochim Biophys Acta. 2005 Sep 15;1725(2):201-12
references.pmid: 15996823
references.citation: Int J Toxicol. 2010 Dec;29(6):569-81
references.pmid: 21076123
references.citation: Neuroscience. 2013 Mar 13;233:118-26
references.pmid: 23291458
references.citation: Antioxid Redox Signal. 2013 Aug 10;19(5):510-6
references.pmid: 22233239
references.citation: J Bioenerg Biomembr. 2008 Oct;40(5):533-9
references.pmid: 18839291
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1930-7
references.pmid: 18417642
references.citation: Toxicol Sci. 2002 Jan;65(1):18-25
references.pmid: 11752681
references.citation: Clin Toxicol (Phila). 2007 Dec;45(8):815-917
references.pmid: 18163234
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1479-85
references.pmid: 18799635
references.citation: Arch Toxicol. 1990;64(8):650-5
references.pmid: 2090033
references.citation: Biochim Biophys Acta. 2009 Jul;1787(7):856-63
references.pmid: 19361483
references.citation: CMAJ. 2008 Aug 12;179(4):312-3
references.pmid: 18695173
references.citation: Anal Biochem. 2005 Jun 1;341(1):40-51
references.pmid: 15866526
references.citation: Br J Pharmacol. 2010 Jun;160(4):941-57
references.pmid: 20590590
references.citation: Nat Rev Mol Cell Biol. 2012 Jul 11;13(8):499-507
references.pmid: 22781905
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10719-24
references.pmid: 20556885
references.citation: Toxicol Sci. 1999 Aug;50(2):287-93
references.pmid: 10478866
references.citation: Br J Pharmacol. 2009 Jul;157(6):944-51
references.pmid: 19422378
references.citation: Biochim Biophys Acta. 2010 Aug;1797(8):1500-11
references.pmid: 20398623
references.citation: Br J Clin Pharmacol. 2010 Jun;69(6):626-36
references.pmid: 20565454
references.citation: Mol Pharmacol. 1967 Jul;3(4):378-85
references.pmid: 6033636
references.citation: Respir Physiol Neurobiol. 2012 Nov 15;184(2):170-7
references.pmid: 22579639
references.citation: Antioxid Redox Signal. 2012 Jul 1;17(1):32-44
references.pmid: 22074253