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A B S T R A C T Rapid hemodialysis of uremic animals may induce a syndrome characterized by increased cerebrospinal fluid (CSF) pressure, grand mal seizures, and electroencephalographic abnormalities. There is a fall in pH and bicarbonate concentration in CSF, and brain osmolality exceeds that of plasma, resulting in a net movement of water into the brain. This syndrome has been called experimental dialysis disequilibrium syndrome. The fall in pH of CSF may be secondary to a fall of intracellular pH (pHi) in brain. Since changes in pHi can alter intracellular osmolality in other tissues, it was decided to investigate brain pHi in uremia, and the effects of hemodialysis. Brain pHi was measured by evaluating the distribution of "4C-labeled dimethadione in brain relative to CSF, while extracellular space was calculated as the MSO4 space relative to CSF. In animals with acute renal failure, brain (cerebral cortex) pHi was 7.06±0.02 (±+SE) while that in CSF was 7.31+-0.02, both values not different from normal. After rapid hemodialysis (100 min) of uremic animals, plasma creatinine fell from 11.8 to 5.9 mg/dl. Brain pHi was 6.89±0.02 and CSF pH was 7.19±0.02, both values significantly lower than in uremic animals (P < 0.01), and there was a 12% increase in brain water content. After slow hemodialysis (210 min), brain pHi (7.01±0.02) and pH in CSF (7.27±0.02) were both significantly greater than values observed after rapid hemodialysis (P < 0.01), and brain water content was normal. None of the above maneuvers had any effect on pHi of skeletal muscle or subcortical white matter.The data show that rapid hemodialysis of uremic dogs is accompanied by a significant fall in pH of CSF and

A B S T R A C T StudiesThe present study was undertaken in order to evaluate the effects of changes in brain Ca"+ on the electroencephalogram (EEG) 1 of normal and acutely uremic dogs. The influence of parathyroidectomy and administration of parathyroid extract on the EEG was also evaluated. METHODSStudies were done in five groups of adult mongrel dogs of both sexes, weighing 15-22 kg, as follows: (a) seven normal dogs; (b) six dogs with uremia of 3.5 days duration; (c) seven normal dogs which received intramuscular injections of parathyroid extract (Eli Lilly & Co., Indianapolis, Ind.), 80 U twice a day for 3.5 days; (d) seven normal dogs which were subjected to thyroparathyroidectomy and received vitamin D3 (Deltalin, Eli Lilly & Co.) in adequate doses to maintain a serum calcium level of 9-11 mg/dl for 7-10 days and were then made uremic for 3.5 days; (c) and six normal dogs which were first subjected to parathyroidectomy, then made uremic, and received parathyroid extract, 100 U four times a day thereafter. The procedures for induction of uremia and for parathyroidectomy have been described elsewhere (1,8). The technique for parathyroidectomy involved simultaneous removal of the thyroid gland, and success of parathyroidectomy was ascertained by a fall in plasma Ca"+ of a least 2 mg/dl within 48 hr.Animals were sedated with one single dose of intravenous diazepam (Valium, Roche Diagnostics Div., Hoffmann-La Roche Inc., Nutley, N. J.), 0.5 mg/kg, then paralyzed with 1 mg/kg of succinylcholine (Anectine, Burroughs Welcome & Co., Research Triangle Park, N. C.) intravenously, and immediately intubated with an endotracheal tube. Mechanical ventilation was carried out with a Harvard Respirator (Harvard Apparatus Co., Inc., Millis, Mass.) at a rate of 25 strokes/min and tidal vol of 8.5 cm3/kg. Arterial pC02 was maintained at about 35 mm Hg by minor changes in the tidal volume.EEG recordings were made with a Beckman Accutrace 8 channel electroencephalograph (Beckman Instruments, Inc., Fullerton, Calif.) with a time constant of 0.3 s and muscle filter set at 30 Hz, using subdermal needle electrodes. Bipolar longitudinal linkages were used in accordance with the standard 10-20 system (9). Recordings of the right and left frontoparietal, frontotemporal, centro-occipital, and occipitotemporal areas were obtained in all animals.At least 3-4 h were allowed between the initial administration of IV diazepam and the EEG recordings. During the recordings, attempts were made to maintain a state of alertness of the dogs, by both manual and auditory stimulation. After the EEG had been obtained, the animals were anesthesized with intravenous sodium pentobarbitol (20-30 mg/kg) and samples of arterial blood, cisternal cerebrospinal fluid (CSF) and brain white and gray matter were obtained as previously described (8).Measurements of Na+, K+, Ca++, Mg++, and water content were made in brain cortical gray matter and subcortical white matter, and of Na+, K+, Ca++, Mg PO04, and creatinine levels in plasma and CSF. The analytical methods...