期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 305, 期 6, 页码 R630-R638出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00218.2013
关键词
control of respiration; hydrogen sulfide; toxicity
类别
资金
- CounterACT Program, National Institutes of Health Office of the Director
- National Institute of Neurological Disorders and Stroke [1R21NS-080788-01]
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 (CgH(2)S, 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 mu M. During NaHS infusion, H2S was primarily present in nonsoluble form in the arterial blood: CMBBH2S was about 50 times higher than CgH(2)S at the lowest levels of exposure and 5 or 6 times at the levels wherein fatal apnea occurred. CgH(2)S averaged only 1.1 +/- 0.7 mu M when breathing increased, corresponding to a CMBBH2S of 11.1 +/- 5.4 mu M. Apnea occurred at CgH(2)S above 5.1 mu M and CMBBH2S above 25.4 mu M. 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.
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