Tolerance of low cerebral intracellular pH in rats during hyperbaric hypercapnia.
OBJECTIVE
Brain acidosis from cerebral ischemia is characterized by average intracellular pH levels of approximately 5.8-6.2, which appear in turn to worsen cellular injury. We report that the brain is not injured when hypercapnia is used to reduce intracellular pH to about 6.2 during adequate oxygenation. A hyperbaric chamber is needed to achieve intracellular pH values so low because inspired CO2 tensions must be increased to approximately 1 atm.


METHODS
Using in vivo phosphorus-31 and proton nuclear magnetic resonance spectroscopy, we measured brain intracellular pH and lactate concentration of rats inside a nonmagnetic polycarbonate chamber at a barometric pressure of 1,500 mm Hg. Intubated rats were ventilated with a 50% O2/50% CO2 gas mixture for specific times. All six rats ventilated for 15 minutes with CO2 tensions of approximately 750 mm Hg woke up without neurological impairment, despite a decrease in intracellular pH to about 6.2. Higher CO2 tensions and longer exposures resulted in cardiovascular collapse and sudden death, followed by the postmortem appearance of brain lactate.


CONCLUSIONS
Brain intracellular pH values near 6.2 can be induced briefly in vivo in ventilated rats without injury under hyperbaric hypercapnic conditions. If attempts are made to lower brain pH in vivo even further by increasing PCO2 beyond 750 mm Hg, mean arterial blood pressure and cerebral blood flow decrease to values incompatible with life.
Department of Pharmaceutical Chemistry, University of California, San Francisco.
Y
Y
Xu
Y
Y
Cohen
L
L
Litt
L H
LH
Chang
T L
TL
James
D000818:Animals; D001923:Brain Chemistry; D002245:Carbon Dioxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006931:Hyperbaric Oxygenation; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology*; D007773:Lactates / Q000032:analysis / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D002245:Carbon Dioxide