There is now abundant evidence that a substantial hydrogen ion gradient exists between extracellular and intracellular water. The mechanism maintaining this gradient is not known, but for most cells it does not appear to be a function of simple Gibbs-Donnan equilibrium. Moreover, under a variety of circumstances, changes in the pH of one fluid compartment may occur without producing comparable changes in the other (1). Apparently, therefore, studies of acid-base metabolism cannot be restricted just to a consideration of extracellular hydrogen ion concentration but should include independent estimates of the pH changes within cells.In vivo studies of intracellular pH in the mammalian species have dealt largely with muscle and erythrocytes. Recently, estimates of whole body intracellular pH have been made in dogs and in humans by the 5,5-dimethyl-2,4-oxazolidinedione (DMO) technique (2, 3), and the pH of brain cells has been measured in rats by the H2CO3-HC03-system (4). However, no systematic study has appeared concerning acid-base regulation in brain cells. In our study the effects of various experimental modifications of extracellular pH on the intracellular pH of brain have been determined in dogs by the DMO technique.The DMO method, first introduced by Waddell and Butler for the indirect measurement of the internal pH of muscle cells (5) ECF nor any agreement concerning the substance to be used in determining brain ECF, we used both endogenous chloride and radiolabeled sulfate spaces as estimates of the extracellular fluid space of the brain. The data obtained in these studies have proven to be relevant not only to acid-base metabolism in the brain but also to the problem of the magniitude of brain extracellular volume. Materials and MethodsDog experiments. Forty-three adult, mongrel dogs weighing between 10 and 14 kg were studied. Each dog was anesthetized with sodium phenobarbital in a dose of 125 mg per kg. After insertion of an endotracheal tube, spontaneous ventilation was abolished with iv succinyl choline and artificial ventilation maintained with either an Etsten or Harvard pump set to deliver approximately 4 L of room air per minute. The kidneys were mobilized through an extraperitoneal approach, and the renal pedicles, including blood vessels and ureters, were ligated. Indwelling polyethylene catheters were placed in a femoral artery and an external jugular vein. The animal's scalp and underlying musculature were "peeled" off the skull, and the left posterior aspect of the bony calvaria was rongeured away. After the exposed dura was excised, from the occipital pole of the left cerebral hemisphere approximately three g of tissue was dissected with a sharp knife. Gel foam was placed in the wound and the cranial defect covered with dry gauze. Bleeding eventually stopped spontaneously after an estimated blood loss of approximately 15 ml. Simultaneous with biopsy of the brain, 30 ml of heparinized arterial blood was collected for chemical analysis. Over a 10-minute period 1.5 g DMO in 30 ml of 5%o glucos...

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