Corbett R, Laptook A, Kim B, Tollefsbol G, Silmon S, Garcia D
Ralph Rogers and Mary Nell Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center at Dallas, 5801 Forest Park Road, Dallas, TX 75235-9085, USA.
Brain Res Dev Brain Res. 1999 Mar 12;113(1-2):37-46. doi: 10.1016/s0165-3806(98)00187-4.
Intraischemic hyperglycemia has different effects on neurologic outcome in mature vs. immature brain, and may reflect differences in the extent or duration of cerebral lactic acidosis. We examined the hypotheses that post-ischemic lactate and acid clearance rates depend on the severity of intraischemic cerebral acidosis, and that rates of clearance change as a function of brain maturation. In vivo 31P and 1H magnetic resonance spectroscopy (MRS) was used to compare intracellular acid and lactate clearance rates in newborn and 1-month old swine following a 14-min episode of transient near-complete global ischemia. In the same animals, in vivo microdialysis was used to determine if extracellular lactate clearance changed as a function of cerebral lactic acidosis or differed between age groups following ischemia. Plasma glucose concentration was altered in individual animals to study a range of intraischemic cerebral lactic acidosis. For both age-groups, maximal brain acidosis and lactosis occurred in the post-ischemia interval, indicating a delay in the re-establishment of oxidative metabolism following ischemia. Clearance half-lives of both cerebral acidosis and lactosis increase as a function of increased intraischemic cerebral acidosis. For either age group, the clearance half-life for acidosis was faster than the half-life for lactate. However, the subgroup of 1-month old swine who experienced severe cerebral acidosis (i.e., pH<6.1) had a longer cerebral lactate clearance half-life as compared to the subgroup of newborn animals with a similar severity of acidosis. In both age groups, there were comparable maximal increases in extracellular lactate concentrations in the post-ischemic period and similar rates of decline from the maximum. These results demonstrate that post-ischemic lactate and acid clearance are altered by the extent of intraischemic acidosis, and the extent of post-ischemic uncoupling between brain acid and lactate clearance increases with advancing age. The transmembrane clearance of lactate was not a prominent mechanism that differentiated lactate clearance rates between newborn and 1-month old swine.
缺血期间高血糖对成熟和未成熟大脑的神经学结局有不同影响，这可能反映了脑乳酸酸中毒程度或持续时间的差异。我们检验了以下假设：缺血后乳酸和酸清除率取决于缺血性脑酸中毒的严重程度，且清除率随脑成熟度而变化。采用体内31P和1H磁共振波谱（MRS）比较新生猪和1月龄猪在经历14分钟短暂近乎完全性全脑缺血发作后的细胞内酸和乳酸清除率。在同一批动物中，采用体内微透析法确定缺血后细胞外乳酸清除率是否随脑乳酸酸中毒而变化，或在缺血后不同年龄组之间是否存在差异。改变个体动物的血浆葡萄糖浓度，以研究一系列缺血性脑乳酸酸中毒情况。对于两个年龄组，最大脑酸中毒和乳酸性酸中毒均发生在缺血后期间，表明缺血后氧化代谢的重新建立存在延迟。脑酸中毒和乳酸性酸中毒的清除半衰期均随缺血性脑酸中毒程度的增加而延长。对于任何一个年龄组，酸中毒的清除半衰期都比乳酸的半衰期快。然而，与酸中毒严重程度相似的新生动物亚组相比，经历严重脑酸中毒（即pH<6.1）的1月龄猪亚组的脑乳酸清除半衰期更长。在两个年龄组中，缺血后细胞外乳酸浓度的最大增加值相当，且从最大值下降的速率相似。这些结果表明，缺血后乳酸和酸清除率受缺血性酸中毒程度的影响，且随着年龄增长，脑酸和乳酸清除之间缺血后解偶联的程度增加。乳酸的跨膜清除不是区分新生猪和1月龄猪乳酸清除率的主要机制。
