LaManna J C, McCracken K A
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Adv Exp Med Biol. 1990;277:335-43. doi: 10.1007/978-1-4684-8181-5_39.
We report here the results of our study of the carbonic anhydrase inhibitor acetazolamide on cerebral vascular and metabolic function, correlated with the effects of this agent on systemic arterial blood gases and pH. We found that the effects of acetazolamide were to increase PaO2, decrease bicarbonate ion concentration and decrease pH. While these effects were maintained for many hours after both high and low dose acetazolamide, the cerebral metabolic and vascular effects of the drug were transient. The central effects of carbonic anhydrase inhibition were consistent with increased oxygen delivery and increased tissue oxygenation. Hypoxia such as encountered at altitude, represents a challenge to the mechanisms which control blood flow in the brain. The decreased arterial oxygen content at altitude is a ventilatory drive which has the effect of 1) increasing somewhat the PaO2; 2) decreasing the PaCO2; 3) alkalinizing the blood. The decreased PaCO2 then leads to decreased CBF compounding the problem of hypoxemia. In this situation, increasing CBF helps to relieve the tissue hypoxia. This has been done by either increased inhalation of CO2 (Harvey et al., 1988) or by acetazolamide (Cain and Dunn, 1966; Forwand et al., 1968). A common feature in both treatments might be increased tissue CO2 retention (Kjällquist et al., 1969; Meyer et al., 1961) and tissue acidification (Heuser et al., 1975). The two treatments are not identical since acetazolamide seems to have additional effects on cerebral metabolism that elevated CO2 does not. Thus, we can deduce that the primary pathologic effects of acute hypoxia are due to the decreased cerebral blood flow produced by hyperventilation-induced hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
我们在此报告对碳酸酐酶抑制剂乙酰唑胺对脑血管及代谢功能的研究结果，并将其与该药物对全身动脉血气和pH值的影响相关联。我们发现，乙酰唑胺的作用是提高动脉血氧分压（PaO2）、降低碳酸氢根离子浓度并降低pH值。虽然高剂量和低剂量乙酰唑胺给药后这些影响会持续数小时，但该药物对脑代谢和血管的影响是短暂的。碳酸酐酶抑制的中枢效应与增加氧输送和提高组织氧合作用一致。诸如在高原遇到的低氧，对控制脑血流的机制构成挑战。高原时动脉血氧含量降低是一种通气驱动，其作用为：1）使PaO2略有升高；2）降低动脉血二氧化碳分压（PaCO2）；3）使血液碱化。降低的PaCO2进而导致脑血流量（CBF）减少，加重了低氧血症问题。在这种情况下，增加CBF有助于缓解组织缺氧。这可通过增加二氧化碳吸入量（哈维等人，1988年）或使用乙酰唑胺（凯恩和邓恩，1966年；福尔万德等人，1968年）来实现。两种治疗方法的一个共同特征可能是组织二氧化碳潴留增加（凯尔克维斯特等人，1969年；迈耶等人，1961年）和组织酸化（霍伊泽尔等人，1975年）。这两种治疗方法并不完全相同，因为乙酰唑胺似乎对脑代谢有额外作用，而升高二氧化碳则没有。因此，我们可以推断急性低氧的主要病理效应是由于过度通气引起的低碳酸血症导致脑血流量减少。（摘要截选至250词）
