インシュリン低血糖状態に関する実験的研究―主として中枢神経系の電気生理学的変化について―

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With the use of unrestrained and unanesthetized cats implanted with electrodes the author observed normal EEG as well as that of the cats under insulin-hypoglycemia. In addition, observations were carried on the influences of some drugs and electrical stimulation on hypoglycemic EEG. The results are as follows. 1. The low voltage fast waves observable in awaking state change to characteristic sleep spindle of abort 12 c/s as the cat falls into sleeping state, and in deeper sleeping state high voltage slow waves appear in the cortex and various nuclei of subcortex. 2. Hypoglycemic state was classified into lethargic, preconvulsive, convulsive and comatose stages on the basis of characteristic behavior, blood-sugar level and EEG. In the lethargic stage, normal EEG from awaking to deep sleeping state appeared in all leads. In the preconvulsive stage, disturbances of sympathetic nervous system and large slow wave burst were characteristic. In the convulsive stage, spikes and sharp waves were predominant, and furthermore, myoclonic jerk in all muscles and occasionally general convulsion broke out suddenly. In the comatose stage, cats were completely relaxed and 1 cycle/sec or less large slow waves appeared on EEG. In this instance when hypoglycemia was in progress, voltage diminished lower and lower. 3. Arousal effect of excitatory agents and amino acids on insulinhypoglycemia in comparison with that of glucose a) General convulsion Only when general convulsion was induced by electrical stimulation, metrazol and megimide, there could be observed hyperglycemia, awaking patterns on EEG and behavioral wakefulness. In comparison with glucose, however, arousal effect was transient and uncertain. b) Amino acids Sodium glutamate next to glucose had hyperglycemic and arousal action on hypoglycemic cats, but its action was not so fast and long as glucose. The greater the dosage of sodium glutamate administered, the more certain was the effect. Fast administration of large dose, however, is dangerous because it is apt to induce general convulsion. GABA (gamma-amino butyric acid) showed transient hyperglycemic action and arousal patterns on EEG, but no essential change took place in behavior. Although GABOB (gamma-amino beta-hydroxybutyric acid) was administered in the convulsive stage, no definite action was seen. 4. Administration of inhibitory agents to insulin-hypoglycemia a) Nembutal Nembutal administered intravenously in the convulsive stage caused spikes and sharp waves on EEG to disappear and then elicited spindle burst. While myoclonic seizures and convulsions were being suppressed, hypoglycemia continued to progress. In the comatose stage Nembutal was non-effective. b) Chlorpromazine (Cp) Although not so effective as Nembutal, an optimal dose of Cp allows hypoglycemia to proceed gradually. Precaution is necessary with this drug because, when a large dose of Cp is injected rapidly into vein in the convulsive state, it is apt to induce convulsion and then the animal cannot be aroused even by administration of glucose.植え込み電極を施しに慢性猫を用いて,正常脳波,インシュリン低血糖状態およびそれに対する中枢神経刺戟, 2, 3のアミノ酸と中枢神経抑制物質の影響を観察した.その結果は次の如くである. 1) 覚醒時に認められる低振巾速波は,猫が眠りに傾くと特徴的な12c/s前後のsleep spindleに変り,更に深睡眠では皮質および皮質下諸核に高電位徐波が出現する. 2) インシュリン低血糖状態は一般状態,血糖値,脳波を基準として,嗜眠期,痙攣前期,痙攣期,昏睡期とに分け得た.嗜眠期には正常猫で認められた深睡眠に至るまでのあらゆる脳波が認められた.痙攣前期は自律神経系の嵐と大徐波のburstを特徴とし,痙攣期は棘・鋭波を盛んに認め,ミオクロヌス攣縮・全身痙攣が起る.昏睡期にはあらゆる刺戟に応ぜず,脳波では1c/s以下の大徐波を認め,更に低血糖状態を続けると電位を減ずる. 3) インシュリン昏睡に対する中枢神経賦活剤およびアミノ酸の覚醒効果を葡萄糖を基準として検討すると, i) 中枢神経刺戟電気刺戟,メトラゾール,メジマイドを用いたが,全身てんかん様痙攣発作を起した時のみ血糖上昇と脳波および一般状態の覚醒を認めた.葡萄糖に較べその効果は一過性不確実であつた. ii) アミノ酸グルタミン酸ソーダは葡萄糖に次いで血糖上昇作用と覚醒作用を持ち,脳波を完全に覚醒パターンに置換しうるが,糖ほど迅速,且持続時間が長くない.この効果はグルタミン酸の投与が多いほど確実であるが,あまり大量を急速に投与すると危険である(全身痙攣を誘発). GABAにも一過性の血糖上昇作用と脳波上の覚醒効果を認めたが,一般状態には変化がない. GABOBを痙攣期に用いたが,確かな抑制作用は認められなかつた. 4) 更にインシュリン低血糖状態に神経抑制物質を加重して検討すると, i) Nembutal痙攣期にNembutalを静注すると,脳波上の棘波・鋭波を消失せしめ,特有な紡錘形の高振巾速波群を生ぜしめ,攣縮及び痙攣を完全に抑制したまま低血糖を進行させる.深昏睡期にはNembutalの影響はない. ii) Chlorpromazine 痙攣前期以後に適当量のCpを適用すると, Nembutalほどではないが,低血糖を静かに進行せしめる.大量のCpを急激に痙攣期の猫に静注すると,痙攣を誘発し易く,その後に糖水を補給しても覚醒しにくい事があるので注意を要する.
1962-07-30

インシュリン低血糖状態に関する実験的研究―主として中枢神経系の電気生理学的変化について―

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