脳虚血病巣組織pHの経時的変化—alkaline shift

CHANGES OF TISSUE pH IN DOG BRAIN DURING ISCHEMIA : ALKALINE SHIFT

I．はじめに

　脳相織pHは脳代謝の変化を反映する有力な生化学的指標のひとつである。一般に脳虚血状態においては嫌気性糖代謝の亢進により，乳酸，ピルビン酸などの酸性代謝産物が増加し組織pHは低下するとされている。しかし，脳虚血の進行とともに組織pHはいかに変化するか，あるいは，一定度の脳虚血組織が，どの部位でも同程度に一様．にアシドーシスになつていくのかといつた疑問はまだ解明されていない。これは脳組織pHの測定方法および一定の梗塞巣の得られる実験モデルの作製が困難であつたためと考えられる。

　最近，小暮はpH指示薬であるneutral red （NR）を用いて脳組織pHの組織化学的分析法^4）を開発した。この方法は手技も容易で，脳断面の各部位のpHの差違を比色によつて一目瞭然にすることができて，きわめて有用である。

Brain pH changes during ischemia were observed by the newly established histochemical technique in Dr. Kogure's laboratory (Miami). The technique utilizes intravascular injection of neutral red as a pH indicator. Its use is based on the fact that neutral red is red in acid and yellow in alkaline pH. Thalamic infarction model in dogs was used in this experiment. The methods of producing this model by temporary occlusions of brain arteries have been published elsewhere.

The animals were anesthetized with sodium thiopental, immobilized with pancronium bromide, and artificially ventilated with room air. Blood gases and blood pH were adjusted to normal. Before the experimental procedure, 3 ml/kg of a 5% saline suspension of neutral red was injected slowly into the femoral artery. After occlusions of cerebral arteries, the brain was frozen in situ by pouring liquid nitrogen into the bottomless cup. The frozen brain was mounted on a cryostat at -20℃ and sliced coronally in 10 it thickness. Color differences in the serial sliced brain surface were observed.

No change in the color was observed in the sham operated brains. Thirty minutes following occlusion, the color of the thalamus is reddish, and it was estimated that this area became acidotic. 1 hour following occlusion, too, the thalamus is acidotic. But 2 hour following occlusion, the color of the thalamus became yellowish, indicative of alkaline shift.

From this experimental results, it is considered that the pH of ischemic brain changes dynamically, that is, ischemic brain becomes acidotic in the early stage of ischemia but with the lapse of time alkaline shift occurrs.