区別低体温（differential hypothermia）処置の脳代謝に及ぼす影響

INFLUENCE OF DIFFERENTIAL HYPOTHERMIA TREATMENT ON THE CEREBRAL METABOLISM

　抄録　区別低体温療法（D．H．）は，全身低体温下に腫瘍部分のみを37℃に保つ，悪性腫瘍に対する補助療法の一つである。本法の正常脳の代謝に及ぼす影響を見る目的で，直腸温23℃の低体温下に，家兎右前頭葉に対し10時間のD．H．処置を行った後，処置側および非処置側脳のglucose,G−6—P,FDP,dihydroxyace—tone phosphate,pyruvate,lactate,ATP,ADP,AMPの測定を酵素法により行った。試料採取は，D．H．処置開始前，開始直後（低体温時），開始後3時間目，6時間目，10時間目，D．H．処置終了後12時間目および36時間目に行った。D．H．処置6時間目までの処置側脳では，対照に比し相対的な代謝亢進が認められ，6時間目での処置側脳でのL／P比は27.6,ECP （energy charge potential）は0.953であった。D．H．処置後10時間目の処置側脳では，glucoseの低下，G−6—Pの著明な増加，L／P比の上昇（47.5），ATPの減少，ADP,AMPの増加が認められ，ECPは0.873に下降していた。　D．H．処置後36時間目では，L／P比は18.7となり，ECPも0.901と回復が認められた。以上より，D．H．処置6時間目までの加温脳の代謝は比較的円滑に営まれていると推測されるが，10時間目になると，解糖系の代謝亢進とエネルギー代謝の破綻を来たしてくるものと推測される。しかしこの代謝破綻も，処置後の経時的代謝patternの変化からみて可逆的なものと考えられ，今回の結果は，10時間のD．H．処置が脳代謝の面から安全に行いうる可能性を示唆するものといえる。

Differential hypothermia (D. H.) treatment was performed on normal rabbit brains and the associ-ated changes in cerebral metabolism were observed in series. Under generalized body hypothermia (rectal temperature : 23℃), a part of the right frontal lobe was maintained at normothermia (37 ±1℃) by heating with microwave irradiation (2.45 GHz). Brain tissues were sampled as follows; before treatment, at the beginning, 3, 6 and 10 hours later, and finally 12 and 36 hours after com-pletion of the 10 hour-treatment. Five rabbits were studied in each group to be 35 as a total sum. In each rabbit, two samples ; one from the nor-mothermic portion and one from the hypothermic portion, were obtained. By using enzymatic analysis, six glycolytic metabolites (glucose, glucose-6-phos-phate, fructoes-1, 6-diphosphate, dihydroxyacetone phosphate, pyruvate, lactate) and three adenine nucleotides (ATP, ADP, AMP) were investigated quantitatively. From these results, the ratio of lactate and pyruvate (L/P ratio) and energy charge potential (ECP) were calculated.

Before the treatment, the L/P ratio was 26.4 and ECP was 0.921. Up to 6 hours after the begin-ning, the metabolic status in the normothermic portion was relatively higher than the hypother-mic portion. Namely, L/P ratio and ECP in the normothermic portion reached 27.6 and 0.953, respectively. On the completion of the 10 hour-treatment, however, glucose decreased considerably, whereas G 6 P increased markedly associated with a L/P ratio of 47. 5. Similarly ATP was decreased, while ADP and AMP were increased, therefore ECP decreased to 0.873. These data indicated tissue hypoxia. On the other hand, 36 hours after the treatment, the L/P ratio recovered completely to 18. 7 and ECP also recovered to 0.901.

These results indicated that metabolism in the normothermic portion was not disturbed up to 6 hours duration of treatment, although it was con-stantly higher than the hypothermic portion. On the completion on the 10 hour-treatment, increase of glycolysis by tissue hypoxia and failure of energy metabolism were observed. However, these changes were considered to be reversible because the results obtained after the treatment indicated reasonable recovery. Therefore it was suggested that 10 hour differential hypothermia treatment on the normal rabbit brains was safe from a view point of glycolytic and energy metabolism.