Although chronic respiratory acidosis is one of the commonest clinical disturbances of acid-base balance, the process of adaptation which it induces has not been extensively investigated. Normal man tolerates prolonged exposure to high CO., tensions poorly and is, therefore, not a suitable subject for study. Recent observations in the rat exposed to a high CO, atmosphere (1,2) have provided much valuable information, but no balance data are available in the dog, the animal which appears more closely to resemble man in its adjustment to other disturbances of acid-base equilibrium. For this reason, and in order to provide a basis for further investigations of chronic hypercapnia in the dog, the present studies of adaptation were undertaken. METHODSEleven balance studies were carried out on 11 healthy female mongrel dogs weighing between 13 and 20 kg. Observations were made during a 4-to 7-day control period and a 6-to 15-day period of exposure to 10 to 13 per cent carbon dioxide (CO2 period).The studies were carried out with the dogs in metabolic cages maintained at a temperature of approximately 150 C inside a small, ventilated room. The cages were covered with a plastic canopy which was left open during the control period. During the CO2 period the canopy was closed, and a gas mixture of C02, 02, and compressed air was delivered into it. The ratio of the gases delivered was regulated manually. The CO2 content of the cages was monitored frequently with a Kwik-Check carbon dioxide analyzer (Burrell Corp.), * Supported in part by grants from the National Heart Institute (H-759 and HTS-5309), the American Heart Association and the Life Insurance Medical Research Fund. which was standardized with gas mixtures whose composition had been determined by the Scholander method.The oxygen content was determined by a Beckman model C oxygen analyzer.On the first day of the CO2 period, the CO2 content of the cage atmosphere was increased to approximately 10 per cent over a period of 3 to 6 hours. Over the next 1 to 2 days the level was raised slowly to the desired range of 11 to 13 per cent. The oxygen concentration was maintained at 20 + 3 per cent throughout.The dogs were removed from the cages each morning for weighing, feeding, collection of urine and feces, cage cleaning, and (on most mornings) arterial blood sampling.During the CO, period they were also removed in the evening so that the daily diet could be fed in two portions. The total time out of the high CO2 atmosphere on each of these days was about 30 minutes. In order to obtain data on the early adaptation to uninterrupted respiratory acidosis, 9 of the dogs were given their entire diet for the first day of the CO2 period 2 to 3 hours before the CO2 tension was raised, and they were then left undisturbed for 24 hours.A synthetic diet was given, consisting (in per cent) of 55 water, 14 casein, 1.5 agar, 8 hydrogenated vegetable oils, 7.5 dextrose, 14 dextrin, and supplementary vitamins. To each 100 g of diet, 9 mEq of potassium was added as neutral phosphate (4 par...

Previous studies in both the rat (1, 2) and the dog (3) have demonstrated that chronic respiratory acidosis induces profound alterations in electrolyte balance, but little is known concerning the changes that occur when the stimulus of hypercapnia is withdrawn. The present experiments were undertaken in order to define the process of recovery, and to determine how it is influenced by the availability of sodium and chloride in the diet. For this purpose, balance studies were carried out in dogs returned to room air after a long period of exposure to a high CO2 atmosphere. METHODSTen balance studies were carried out in 10 healthy female mongrel dogs weighing between 13 and 20 kg. The experimental procedure, analytical methods, and calculation of the balance data were the same as those described in the preceding paper (3). In order to study the influence of sodium and chloride intake, the animals were divided into three groups whose diet was identical except in the following respects: 1) 4 dogs received 50 to 70 mEq of sodium and chloride daily (high-salt group); 2) 4 dogs received approximately 5 mEq of sodium and 3 mEq of chloride daily (low-salt group); in 3 this diet was supplemented by 60 to 120 mmoles of sodium chloride daily in the latter part of the study period; 3) 2 dogs received a diet identical with that of the low-salt group except that sufficient potassium chloride was added in lieu of potassium phosphate to raise the daily chloride intake to 13 mEq.Seven of the animals were among those described in the preceding paper on adaptation to hypercapnia

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1. The renal clearance of salicylate has been measured in two groups of patients undergoing treatment by alkaline diuresis for salicylate poisoning. One group received mannitol and sodium lactate, the other acetazolamide and sodium bicarbonate.2. The relationship between urine pH and salicylate clearance was found to be the same in both groups and similar to that shown at non-toxic concentrations in the blood by previous workers.3. The influence of the rate of urine flow on the relationship between salicylate clearance and urine pH was also shown to be similar to that found at non-toxic concentrations in the blood.Although alkaline diuresis is now widely accepted as the most effective method of hastening the renal excretion of salicylate, very little is known about its effect on the clearance of this substance in patients with salicylate poisoning. The observations that form the main basis of alkaline diuretic treatment were made at therapeutic blood concentrations in human volunteers (Macpherson, Milne & Evans, 1955;Gutman, Yu & Sirota, 1955) and in dogs (Weiner, Washington & Mudge, 1959). They revealed a linear relationship between log salicylate clearance and urine pH, with a fourfold increase in clearance for each pH unit. There was also a rise in clearance with increasing urine flow, though this effect was relatively small at high urine pH. These observations were consistent with what has become the accepted theory of the renal excretion of weak acids and bases (Milne, Scribner & Crawford, 1958).The present paper reports measurements of salicylate clearance in patients undergoing treatment for salicylate poisoning, at blood salicylate concentrations up to five times higher than those in the human volunteers studied by Macpherson et al. (1955). For obvious reasons, the conditions were neither as uniform nor as stable as in planned experiments. The observations are nevertheless noteworthy because they confirm the predicted relationship between salicylate clearance and pH, and because oftheir relevance to the treatment of salicylate poisoning.

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