Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat

To ascertain the effect of extreme hypercapnia on perinatal hypoxic-ischemi c brain damage, 7-d-postnatal rats were exposed to unilateral common caroti d artery occlusion followed by hypoxia with 8% oxygen combined with 3, 12, or 15% carbon dioxide (CO2) for 2 h at 37 degreesC, Survivors underwent neu ropathologic examination at 30 d of postnatal age, and their brains were ch aracterized as follows: 0 = normal; 1 = mild atrophy; 2 = moderate atrophy; 3 = cystic infarct with external dimensions <3 mm; and 4 = cystic infarct with external dimensions >3 mm. The width of the cerebral hemisphere ipsila teral to the carotid artery occlusion also was determined on a posterior co ronal section and compared with that of the contralateral hemisphere to asc ertain the severity of cerebral atrophy/cavitation, CO2 tensions averaged 5 .08, 11.1, and 13.2 kPa in the 3, 12, and 15% CO2-exposed animals, respecti vely, during hypoxia-ischemia (HI), Neuropathologic results showed that imm ature rats exposed to 3 and 12% CO2 had similar severities of brain damage. In contrast, rat pups exposed to HI combined with 15% CO2 were significant ly more brain damaged than littermates exposed to 3% CO2. Specifically, eig ht of 14 animals exposed to 15% CO2 showed cystic infarcts (grades 3 and 4) , whereas none of 14 littermates exposed to 3% CO2 developed cystic infarct s (p < 0.01). Analyses of coronal width ratios at each CO2 exposure provide d results comparable with those of the gross neuropathology scores. Cerebra l blood flow (CBF), measured at 90 min of HI, was lowest in those immature rats exposed to 15% CO2 compared with control (p = 0.04), with higher value s in those rat pups exposed to 3 and 12% CO2. The findings indicate that 7- d-postnatal rats exposed to HI with superimposed 12% CO2 are neither less n or more brain damaged than littermates exposed to 3% CO2 (normocapnia). In contrast, animals exposed to 15% CO2 are the most brain damaged of the thre e groups. Presumably, extreme hypercapnia produces more severe cardiovascul ar depression than is seen in animals subjected to lesser degrees of hyperc apnia; the cardiovascular depression, in turn, leads to greater cerebral is chemia and ultimate brain damage.