Treatment for Complete Global Cerebral Ischemia

虚血後に対処する脳治療法と虚血負荷前に予め処置しておく脳保護法との違い, 全脳虚血と部分虚血の違いを解説し, この総説では完全全脳虚血の治療法につき述べることを先ず示した。次いで, 虚血によるこれまで解っている病態変化は, 虚血後脳低潅流, 細胞内カルシウムの異常増加, 興奮性アミノ酸, 活性酸素, プロスタグランジン系産物, NO, 種々のサイトカインなどの増加が主なるものであり, それらに対処すべくカルシウム拮抗薬, 興奮性アミノ酸拮抗薬を含み試みられた種々の治療法につき解説した。しかし, 何れの薬物も単独投与では劇的効果を示したものはなく, カルシウム拮抗薬と興奮性アミノ酸拮抗薬または鉄キレート薬の併用がより有効であった。軽度低体温化(34℃)が虚血解除後ごく早期に達成されるならば有効である。一方高圧酸素療法とカルシウム拮抗薬との併用ではこれまで示された最高の治療効果を示している。早期の臨床検討が期待される。Since many recent studies have suggested that the brain may tolerate ischemic insults of much longer duration than previously imagined, numerous experimental investigations have been carried out on the pathophysiology and therapy of brain ischemia. The major pathophysiologic changes associated with brain ischemia have been reported to include postischemic hypoperfusion, abnormally increased levels of intracellular calcium ions, and increases in excitatory amino acids (glutamate and aspartate), free radicals, arachidonic acid derivatives (prostaglandins, leukotrienes), nitric oxide (NO), and cytokines (TNF, PAF, interleukins, etc.). To counteract these abnormal changes and minimize ischemic damage to the brain, many drugs have been administered during the postischemic period. However, remarkable efficacy has not been demonstated for any drug. The combined use of drugs, such as a calcium channel blocker with an NMDA antagonist or with an iron chelate, provided better efficacy than did treatment with any single agent. Mild hypothermia (34℃) may be effective, provided that hypothermia is achieved immediately after the ischemic insult. Hyperbaric oxygenation combined with nicardipine infusion seems to be the most effective treatment reported to date, and clinical trials of this combination are encouraged