CEREBRAL OXIDATIVE-METABOLISM AND BLOOD-FLOW DURING ACUTE HYPOGLYCEMIA AND RECOVERY IN UNANESTHETIZED RATS
CEREBRAL OXIDATIVE-METABOLISM AND BLOOD-FLOW DURING ACUTE HYPOGLYCEMIA AND RECOVERY IN UNANESTHETIZED RATS
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DOI：
10.1111/j.1471-4159.1982.tb08643.x
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发表时间：
1982-01-01
影响因子：
4.7
通讯作者：
DUFFY, TE
中科院分区：
文献类型：
--
作者：
GHAJAR, JBG;PLUM, F;DUFFY, TE
在胰岛素诱导的恒定低血糖水平下，未麻醉的大鼠会产生进行性神经抑制，导致昏迷。在低血糖昏睡期间，大脑中的高能磷酸盐浓度保持正常，但 ATP 在昏迷期间下降了 6%，在昏迷期间下降了 40%（以等电脑电图为特征）。低血糖期间脑血流量 (CBF) 保持正常，而 O2 (CMRO2) 和葡萄糖 (CMRglucose) 的脑代谢率分别下降 45% 和 73%，表明非葡萄糖燃料发生氧化。 CMRO2 和 CMR 葡萄糖与血浆葡萄糖的关系图表明，当血浆葡萄糖浓度低于 2.5 mM 时，替代底物的氧化增加（CMRO2/CMR 葡萄糖升高）。低血糖昏迷期间大脑对β-羟基丁酸的摄取增加，并且其完全氧化可以解释CMRO2超过葡萄糖利用的原因。脑氨是氨基酸代谢的副产品，在低血糖昏迷期间达到的水平足以使血糖正常的动物产生昏迷。给予葡萄糖后恢复的速度和程度取决于低血糖的持续时间和动物治疗前的神经状态。葡萄糖输注 10 分钟后，昏迷大鼠中适度降低的 ATP 水平完全恢复，与动物明显完全的神经系统恢复相似。处于低血糖昏迷状态一分钟或更短时间的大鼠完全恢复了大脑中的高能磷酸盐浓度。当血浆葡萄糖正常化延迟超过昏迷 1 分钟时，CMRO2 仍处于抑制状态，CBF 降至对照的 40%，并且高能底物未能正常化。与氧化代谢和血流抑制相一致，即使在输注葡萄糖1小时后，神经功能和脑电图仍然异常。低血糖昏迷的第一分钟内可能会发生不可逆的脑损伤。
Progressive neurological depression leading to coma was produced in unanesthetized rats at a constant level of hypoglycemia induced by insulin. High-energy phosphate concentrations in brain remained normal during hypoglycemic lethargy, but ATP declined by 6% during stupor and by 40% during coma that was characterized by an isoelectric EEG. Cerebral blood flow (CBF) remained normal during hypoglycemia whereas the cerebral metabolic rates for O2 (CMRO2) and glucose (CMRglucose) decreased by 45 and 73%, respectively, indicating oxidation of nonglucose fuels. A plot of CMRO2 and CMRglucose vs. plasma glucose indicated increasing oxidation of alternate substrates (elevated CMRO2/CMRglucose) at plasma glucose concentrations below 2.5 mM. Cerebral uptake of .beta.-hydroxybutyrate increased during hypoglycemic stupor and its complete oxidation could account for the CMRO2 in excess of glucose utilization. Brain ammonia, a byproduct of amino acid metabolism, reached a level during hypoglycemic coma sufficient to produce coma in normoglycemic animals. The rate and degree of recovery after glucose administration depended on the duration of hypoglycemia and the pretreatment neurological state of the animal. Following 10 min of glucose infusion, ATP levels that were modestly depressed in stuporous rats recovered fully, paralleling the animals'' apparently full neurological recovery. Rats that had been in hypoglycemic coma for 1 min or less fully recovered high-energy phosphate concentrations in brain. When normalization of plasma glucose was delayed for more than 1 min of coma, the CMRO2 remained depressed, CBF decreased to 40% of control and high-energy substrates failed to normalize. In keeping with the depression of oxidative metabolism and blood flow, neurological function and the EEG remained abnormal even after 1 h of glucose infusion. Irreversible brain injury may develop within the 1st min of hypoglycemic coma.