Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.
Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.
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DOI：
10.1542/peds.95.6.868
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发表时间：
1995-06
期刊：
影响因子：
8
通讯作者：
R. Vannucci;J. Towfighi;D. Heitjan;R. Brucklacher
中科院分区：
文献类型：
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作者：
R. Vannucci;J. Towfighi;D. Heitjan;R. Brucklacher
背景和目的临床研究表明，呼吸窘迫综合征需要机械通气的早产儿，如果在呼吸管理过程中发生低碳酸血症，则发生脑室周围白质软化的风险增加。问题仍然是低碳酸血症对缺氧缺血性脑损伤的作用以及高碳酸血症是否具有神经保护作用。方法出生后7天的大鼠进行单侧颈总动脉结扎，然后暴露于全身缺氧8%的氧气（O2）与0，3，6，或9%的二氧化碳（CO2）在37 ℃下2.5小时。存活者在出生后30天进行神经病理学检查，其大脑分类如下：0 =正常; 1 =轻度萎缩; 2 =中度萎缩; 3 =颈动脉结扎同侧大脑半球3 mm处的萎缩伴囊性空洞。还在后冠状面上确定同侧半球的宽度，并与对侧半球的宽度进行比较，以确定脑萎缩/空洞的严重程度。数据用线性模型进行分析。结果：在全身缺氧期间，暴露于0、3、6和9%CO2的动物的CO2张力平均分别为26、42、54和71 mm Hg。缺氧期间的血氧分压在四组之间没有差异，平均为34.7 mm Hg。神经病理学结果显示，30/38（79%）暴露于3%CO2的大鼠显示无或轻度脑损伤，而对照组（0%CO2）为13/33（39%）。与14只对照组相比，仅4只暴露于CO2的大鼠幼仔发生囊性空化（P = .001）。在6%CO2暴露下，与对照组相比，所有20只大鼠幼仔均未显示损伤或轻度萎缩（P < .001）;在9%CO2暴露下，19/23（83%）大鼠幼仔与对照组相比未显示损伤或轻度损伤（P < .001）。数据还显示，暴露于6%CO2的未成年大鼠的脑损伤减少最多，9%CO2的保护作用略低（P = 0.012），后者与吸入3%CO2的动物脑损伤的严重程度相当。每次CO2暴露时冠状宽度比的分析提供了与大体神经病理学评分相当的结果。结论：结果表明，在未成熟大鼠模型中，正常碳酸血症的脑缺氧缺血与严重脑损伤的相关性低于低碳酸血症的脑缺氧缺血，轻度高碳酸血症比正常碳酸血症更具保护作用。在实验模型中的发现值得进一步的动物研究以及对患病新生人类婴儿的治疗管理的临床重新评估。
BACKGROUND AND OBJECTIVE Clinical investigations suggest that premature infants who require mechanical ventilation from respiratory distress syndrome are at increased risk for periventricular leukomalacia if hypocapnia occurs during respiratory management. The question remains as to the contribution of hypocapnia to hypoxic-ischemic brain damage and whether or not hypercapnia is neuroprotective. METHODS Seven-day postnatal rats underwent unilateral common carotid artery ligation followed thereafter by exposure to systemic hypoxia with 8% oxygen (O2) combined with either 0, 3, 6, or 9% carbon dioxide (CO2) for 2.5 hours at 37 degrees C. Survivors underwent neuropathologic examination at 30 days of postnatal age, and their brains were categorized as follows: 0 = normal; 1 = mild atrophy; 2 = moderate atrophy; 3 = atrophy with cystic cavitation 3 mm of the cerebral hemisphere ipsilateral to the carotid artery ligation. The width of the ipsilateral hemisphere also was determined on a posterior coronal section and compared with that of the contralateral hemisphere to ascertain the severity of cerebral atrophy/cavitation. Data were analyzed by linear models. RESULTS CO2 tensions averaged 26, 42, 54, and 71 mm Hg in the 0, 3, 6, and 9% CO2 exposed animals, respectively, during systemic hypoxia. Blood O2 tensions during hypoxia were not different among the four groups and averaged 34.7 mm Hg. Neuropathologic results showed that 30/38 (79%) rats exposed to 3% CO2 showed either no or mild brain damage compared with 13/33 (39%) controls (0% CO2). Cystic cavitation occurred in only four CO2 exposed rat pups compared with 14 controls (P = .001). At 6% CO2 exposure, all of 20 rat pups showed either no damage or mild atrophy compared with controls (P < .001); and at 9% CO2 exposure, 19/23 (83%) rat pups showed no or mild damage compared with controls (P < .001). The data also showed that the greatest reduction in brain damage occurred in immature rats exposed to 6% CO2 with slightly less protection at 9% CO2 (P = .012), the latter comparable with the severity of brain damage sustained by animals inhaling 3% CO2. Analyses of coronal width ratios at each CO2 exposure provided results comparable with those of the gross neuropathology scores. CONCLUSIONS The results indicate that in an immature rat model normocapnic cerebral hypoxia-ischemia is associated with less severe brain damage than in hypocapnic hypoxia-ischemia and that mild hypercapnia is more protective than normocapnia. The findings in an experimental model merit further animal investigations as well as a clinical reappraisal of the ventilatory management of sick newborn human infants.