抗氧化剂可预防氟烷亚麻醉剂量对男性急性低氧通气反应的抑制作用。
Antioxidants prevent depression of the acute hypoxic ventilatory response by subanaesthetic halothane in men.
作者信息
Teppema Luc J, Nieuwenhuijs Diederik, Sarton Elise, Romberg Raymonda, Olievier Cees N, Ward Denham S, Dahan Albert
机构信息
Department of Physiology, Leiden University Medical Centre, The Netherlands.
出版信息
J Physiol. 2002 Nov 1;544(3):931-8. doi: 10.1113/jphysiol.2002.025999.
We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and alpha-tocopherol (200 mg, P.O.) on the depressant effect of subanaesthetic doses of halothane (0.11 % end-tidal concentration) on the acute isocapnic hypoxic ventilatory response (AHR), i.e. the ventilatory response upon inhalation of a hypoxic gas mixture for 3 min (leading to a haemoglobin saturation of 82 +/- 1.8 %) in healthy male volunteers. In the first set of protocols, two groups of eight subjects each underwent a control hypoxic study, a halothane hypoxic study and finally a halothane hypoxic study after pretreatment with AOX (study 1) or placebo (study 2). Halothane reduced the AHR by more than 50 %, from 0.79 +/- 0.31 to 0.36 +/- 0.14 l min(-1) %(-1) in study 1 and from 0.79 +/- 0.40 to 0.36 +/- 0.19 l min(-1) %(-1) in study 2, P < 0.01 for both. Pretreatment with AOX prevented this depressant effect of halothane in the subjects of study 1 (AHR returning to 0.77 +/- 0.32 l min(-1) %(-1), n.s. from control), whereas placebo (study 2) had no effect (AHR remaining depressed at 0.36 +/- 0.27 l min(-1) %(-1), P < 0.01 from control). In a second set of protocols, two separate groups of eight subjects each underwent a control hypoxic study, a sham halothane hypoxic study and finally a sham halothane hypoxic study after pretreatment with AOX (study 3) or placebo (study 4). In studies 3 and 4, sham halothane did not modify the control hypoxic response, nor did AOX (study 3) or placebo (study 4). The 95 % confidence intervals for the ratio of hypoxic sensitivities, (AOX + halothane) : halothane in study 1 and (AOX - sham halothane) : sham halothane in study 3, were [1.7, 2.6] and [1.0, 1.2], respectively. Because the antioxidants prevented the reduction of the acute hypoxic response by halothane, we suggest that this depressant effect may be caused by reactive species produced by a reductive metabolism of halothane during hypoxia or that a change in redox state of carotid body cells by the antioxidants prevented or changed the binding of halothane to its effect site. Our findings may also suggest that reactive species have an inhibiting effect on the acute hypoxic ventilatory response.
我们研究了抗氧化剂（AOX）抗坏血酸（2克，静脉注射）和α-生育酚（200毫克，口服）对亚麻醉剂量氟烷（呼气末浓度0.11%）对健康男性志愿者急性等碳酸性低氧通气反应（AHR）的抑制作用，即吸入低氧混合气体3分钟（导致血红蛋白饱和度为82±1.8%）时的通气反应。在第一组实验方案中，两组各8名受试者分别进行了对照低氧研究、氟烷低氧研究，最后在预先使用AOX（研究1）或安慰剂（研究2）预处理后进行氟烷低氧研究。在研究1中，氟烷使AHR降低了50%以上，从0.79±0.31降至0.36±0.14升·分钟⁻¹·%⁻¹，在研究2中从0.79±0.40降至0.36±0.19升·分钟⁻¹·%⁻¹，两者P均<0.01。在研究1的受试者中，预先使用AOX可防止氟烷的这种抑制作用（AHR恢复到0.77±0.32升·分钟⁻¹·%⁻¹，与对照无显著差异），而安慰剂（研究2）则无作用（AHR仍被抑制在0.36±0.27升·分钟⁻¹·%⁻¹，与对照相比P<0.01）。在第二组实验方案中，两组各8名受试者分别进行了对照低氧研究、假氟烷低氧研究，最后在预先使用AOX（研究3）或安慰剂（研究4）预处理后进行假氟烷低氧研究。在研究3和4中，假氟烷未改变对照低氧反应，AOX（研究3）或安慰剂（研究4）也未改变。研究1中低氧敏感性比值（AOX + 氟烷）:氟烷以及研究3中（AOX - 假氟烷）:假氟烷的95%置信区间分别为[1.7, 2.6]和[1.0, 1.2]。由于抗氧化剂可防止氟烷降低急性低氧反应，我们认为这种抑制作用可能是由氟烷在低氧时还原代谢产生的活性物质引起的，或者是抗氧化剂改变了颈动脉体细胞的氧化还原状态，从而阻止或改变了氟烷与其作用位点的结合。我们的研究结果还可能表明活性物质对急性低氧通气反应有抑制作用。
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