Arieli, R., G. Rashkovan, Y. Moskovitz, and O. Ertracht. PCO 2 threshold for CNS oxygen toxicity in rats in the low range of hyperbaric PO2. J Appl Physiol 91: [1582][1583][1584][1585][1586][1587] 2001.-Central nervous system (CNS) oxygen toxicity, as manifested by the first electrical discharge (FED) in the electroencephalogram, can occur as convulsions and loss of consciousness. CO 2 potentiates this risk by vasodilation and pH reduction. We suggest that CO2 can produce CNS oxygen toxicity at

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... a PO2 that does not on its own ultimately cause FED. We searched for the CO2 threshold that will result in the appearance of FED at a PO2 between 507 and 253 kPa. Rats were exposed to a PO2 and an inspired PCO2 in 1-kPa steps to define the threshold for FED. The results confirmed our assumption that each rat has its own PCO2 threshold, any PCO2 above which will cause FED but below which no FED will occur. As PO2 decreased from 507 to 456, 405, and 355 kPa, the percentage of rats that exhibited FED without the addition of CO2 (F0) dropped from 91 to 62, to 8 and 0%, respectively. The percentage of rats (F) having FED as a function of PCO2 was sigmoid in shape and displaced toward high PCO2 with the reduction in PO2. The following formula is suggested to express risk as a function of PCO2 and PO2 where P 50 is the PCO2 for the half response and N is power. A small increase in PCO2 at a PO2 that does not cause CNS oxygen toxicity may shift an entire population into the risk zone. Closed-circuit divers who are CO2 retainers or divers who have elevated inspired CO2 are at increased risk of CNS oxygen toxicity. hyperbaric oxygen; electroencephalogram; convulsions; diving; central nervous system CENTRAL NERVOUS SYSTEM (CNS) oxygen toxicity can appear in humans exposed to oxygen pressures above 180 kPa as convulsions (similar to epileptic seizures, grand mal) and loss of consciousness without any premonitory symptoms. It is known that the risk of CNS oxygen toxicity is greater when CO 2 is present in the inspired gas (2, 7, 8, 13, 19, 21, 23) or in tissue (25) , mainly due to its effect on cerebral vasodilatation and increased brain tissue PO 2 (15) and acidity-enhanced reactive oxygen species (ROS) (6, 11, 22) . In underwater diving where the risk of CNS oxygen toxicity is also encountered due to elevated PO 2 , other extraneous circumstances leading to the elevation of PCO 2 may increase this risk even more (20, 24). We have recently shown (2) that the latency to CNS oxygen toxicity decreased linearly as a function of the inspired PCO 2 and that it may even be affected by a PCO 2 as low as 1 kPa. These studies were conducted using PO 2 that cause CNS oxygen toxicity without the presence of CO 2 in the inspired gas. PO 2 during closedcircuit diving and hyperbaric oxygen therapy is usually kept at levels that do not cause CNS oxygen toxicity. All of the studies on the effect of CO 2 on CNS oxygen toxicity were conducted at a PO 2 that can cause CNS oxygen toxicity without the added effect of CO 2 (7, 9, 10, 23). Almost nothing is known about the effect of CO 2 on CNS oxygen toxicity at a PO 2 below the level that will on its own produce this toxic effect. We hypothesized that CO 2 , which causes vasodilatation in the brain and therefore increases the tissue oxygen pressure, together with acidity-enhanced production of ROS (6, 11, 22) , would cause CNS oxygen toxicity at a PO 2 below the level that causes CNS oxygen toxicity on its own. The level of inspired CO 2 at which the breach occurs (the threshold for CNS oxygen toxicity) is the subject of the present study. The first electrical discharge (FED), which precedes the clinical convulsions, in the electroencephalogram (EEG) is a well-defined phenomenon and may be used to validate the effect of PCO 2 on CNS oxygen toxicity. We used a previously described rat model (1, 3, 4) to investigate the effect of CO 2 in the inspired gas on the threshold for CNS oxygen toxicity as a function of PO 2 . METHODS Animals White male Sprague-Dawley rats had EEG electrodes implanted under equithensin anesthesia (0.3 ml/100g body wt ip) 3 days before the experiment. The electrodes were stain-