Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogs.
Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogs.
复制标题
脑室内注射右美托咪定可减少犬常氧和缺氧期间的脑血流量。
DOI：
10.1097/00000539-199701000-00026
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发表时间：
1997
影响因子：
5.7
通讯作者：
Traystman,RJ
中科院分区：
文献类型：
--
作者：
McPherson,RW;Koehler,RC;Kirsch,JR;Traystman,RJ
我们检验了一个假设，即中枢给药α 2受体激动剂可以改变脑血管对缺氧的反应，而没有证据表明药物的全身吸收。用1.4%异氟烷麻醉比格犬，并在用模拟脑脊液（CSF组，n= 5）或右美托咪定（100 μ g/mL;总剂量300 μ g; DEX组，n= 6）进行脑室-脑池灌注之前和之后暴露于缺氧性缺氧（PaO 2约22 mm Hg）。控制脑灌注压、动脉血氧分压（PaCO 2）和动脉血氧含量，测定局部脑血流量（CBF）和全脑氧代谢率（CMRO 2）。另一组（n= 5）采用3 H可乐定脑室-脑池灌流法评价药物分布。在模拟CSF组中，在基线条件下缺氧期间和CSF输注后，流向大脑半球的流量增加：66+/-8至170+/-15 mL [中心点] min-1 [中心点] 100 g-1（基线值的265% ± 24%），83 ± 9至154 ± 14 mL [中心点] min-1 [中心点] 100 g-1（CSF输注后值的201% ± 54%）。DEX使大脑半球的常氧血流量从76+/-6降至44+/-4 ml [中心点] min（-1）[中心点] 100 g-1，其他区域的减少幅度相似。DEX后缺氧时各区域绝对流量为DEX前的52%~ 55%（P< 0.05）。然而，由于DEX也降低了常氧CBF，缺氧期间流量增加的百分比在DEX之前和之后相似。CMRO 2在DEX前不受缺氧的影响。然而，DEX后，缺氧导致脑氧输送显著减少（CSF组为5.2+/-1.0 vs 13.7+/-2.3 ml [中心点] min-1 [中心点] 100 g-1）和CMRO 2（2.5+/-0.6 vs 3.9+/-0.6 ml [中心点] min-1 [中心点] 100 g-1）。脑室内给药的3 H-可乐定在脑室周围脑结构（如尾状核、背侧脑干）中的区域蓄积最大，大脑皮质中的浓度约为同侧尾状核中浓度的1%。我们的结论是，集中管理的DEX减少脑血流量在常氧和防止缺氧期间足够的氧气输送。DEX诱导的CBF减少的机制不是代谢介导的，因为CMRO 2在常氧期间保持在对照值，尽管血流量显著减少。我们认为，在DEX治疗的狗缺氧过程中CMRO 2的减少是氧输送减少的结果，而不是缺氧过程中观察到的CBF减少的潜在机制。
We tested the hypothesis that a centrally administered alpha 2-receptor agonist could alter the cerebrovascular response to hypoxia, without evidence of systemic absorption of the drug. Beagle dogs were anesthetized with 1.4% isoflurane and exposed to hypoxic hypoxia (PaO 2 approximately 22 mm Hg) before and after ventricular-cisternal perfusion with mock cerebrospinal fluid (CSF group, n= 5) or dexmedetomidine (100 micro g/mL; total dose 300 micro g; DEX group, n= 6). Cerebral perfusion pressure, PaCO 2 and arterial oxygen content were controlled and regional cerebral blood flow (CBF; microspheres) and global cerebral metabolic rate for oxygen consumption (CMRO 2) were measured. In another group (n= 5), drug distribution under the experimental conditions was assessed by 3 H-clonidine administered by ventricular-cisternal perfusion. In the mock CSF group, flow to the cerebral hemispheres increased during hypoxia under baseline conditions and after CSF infusion: 66+/-8 to 170+/-15 mL [center dot] min-1 [center dot] 100 g-1 (265%+/-24% of baseline value), 83+/-9 to 154+/-14 mL [center dot] min-1 [centered dot] 100 g-1 (201%+/-54% of post-CSF infusion value). DEX decreased normoxic flow in the cerebral hemispheres from 76+/-6 to 44+/-4 ml [center dot] min (-1)[center dot] 100 g-1 with decreases in other regions of similar magnitude. After DEX, the absolute flow in all regions during hypoxia was 52%-55% of that prior to DEX (P< 0.05). However, because DEX also decreased normoxic CBF, the percent increase in flow during hypoxia was similar before and after DEX. CMRO 2 was not affected by hypoxia prior to DEX. However, after DEX, hypoxia caused a marked reduction in cerebral oxygen delivery (5.2+/-1.0 vs 13.7+/-2.3 ml [center dot] min-1 [center dot] 100 g-1 for the CSF group) and CMRO 2 (2.5+/-0.6 vs 3.9+/-0.6 ml [center dot] min-1 [center dot] 100 g-1). Regional accumulation of intraventricularly administered 3 H-clonidine was greatest in periventricular brain structures (eg, caudate nucleus, dorsal brainstem), and the concentration in the cerebral cortex was approximately 1% of the concentration in the ipsilateral caudate nucleus. We conclude that centrally administered DEX reduces CBF during normoxia and prevents adequate oxygen delivery during hypoxia. The mechanism of DEX-induced CBF reduction is not metabolically mediated, since CMRO 2 is maintained at control values during normoxia despite the significant blood flow reduction. We believe that the reduction in CMRO 2 during hypoxia in DEX-treated dogs is the result of a reduction of oxygen delivery rather than the underlying mechanism for the observed reduction in CBF during hypoxia.