Dinitrophenolによる脳腫脹及び酸化的燐酸化のuncoupling

BRAIN SWELLING AND INCREASE IN CEREBRAL OXYGEN CONSUMPTION PRODUCED BY 2,4-DINITROPHENOL

I．はじめに

　実験的脳硬塞及び脳腫脹において脳酸素消費量測定中，脳波の悪化にも拘らず脳酸素消費量の増大する解離現象がみられ^1,2）我々はこの原因を①酸化的燐酸化のuncoupling②酸素負債，③測定上脳血流増加が実際より多く評価されたための測定誤差，のいずれかと考えたが，三者のうちこの現象の原因としては②の酸化的燐酸化のuncouplingが最も確からしく思われたので，これを確かめるため，酸化的燐酸化のuncouplerとして有名な2-4,dinitrophenolを猿の内頸動脈より持続注入して，脳腫脹の発生，脳波の平坦化及び脳酸素消費量の異常増大を得，これを統計学的に検討した。又dinit—rophenolによる脳腫脹発生前後の脳血管CO₂反応性及び過呼吸による反応性とも併せて検討した。

Decreased energy production despite abnormallyincreased oxygen consumption is known to occurin a state called uncoupling of oxidative phospho-rylation. An abnormal increase in cerebral oxygenconsumption observed during development of brainswelling after experimental ischemia promoted thepresent study. A known uncoupler, 2, 4-dinitro-phenol, was slowly infused into one carotid arteryuntil slowing was observed in electroencephalogram(EEG) in 9 monkeys. The dosis ranged from 8mg/kg to 40 mg/kg. Cerebral blood flow (CBF)was measured with electromagnetic flowmeters andarterio-venous oxygen difference with Guyton'sanalyzer. Two animals died of heart failure duringinfusion. EEG became flat in remaining 7 animalsconcomitant with large increases in cerebral oxygenconsumption (CMRO) and in intracranial pressure.Brain swelling was confirmed at autopsy. Similarphenomenon was also observed after status epi-lepticus in another monkey. Increases in CMROand in intracranial pressure (ICP) was accompaniedby flat EEG. This large increase in CMRO₂ wasnot attributed to undue overestimation of CBF,since a decrease in CMRO₂ was confirmed despitelarge increase in CBF in still other monkey duringinhalation of 25% CO₂ using the same measuringtechnique.