The effects of continous intravenous infusion of factor VIII were studied under varied conditions in five children with classic haemophilia. Factor‐VIII activity was stable at room temperature (73–76°F) up to 12 hr in cryoprecipitates from fresh plasma and up to 27 hr in glycine‐precipitated fractions (Fraction AA and Method 4, Hyland). Constant infusion (17 ml/hr) of different concentrations of these fractions produced levels of plasma factor‐VIII activity which were proportional to the dose‐rate and became relatively steady after 12‐18 hr. In separate studies of two of the subjects, dental extraction and laminectomies were uneventfully supported by an initial dose of factor VIII followed by continuous infusions. It is suggested that continuous intravenous infusion of factor VIII is useful for studying the regulation of factor‐VIII levels in plasma and for maintaining steady plasma factor‐VIII activity during replacement therapy.

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Sodium appearing in the urine presumably represents the difference between the amount filtered at the glomerulus and that which leaves the tubular lumen as the filtrate courses through the nephron. The rate of urinary sodium excretion (UNaV) can be modified, therefore, by changes in the filtered load [glomerular filtration rate (GFR) x plasma sodium concentration (PNa)], or the degree of tubular reabsorption, or both.Since UNaV under most circumstances represents only about 1%1o of the filtered load, it is evident that minor changes in filtered load might result in major changes in UNaV. It is not possible at present to assess small changes in filtered load of sodium because of the magnitude of error involved in measuring GFR. Thus, it is not reasonable to ascribe a change in UNaV to a variation in tubular reabsorption simply because there is no apparent change in the filtered load. Furthermore, the uncertainty involved in measuring small changes in filtered load of sodium has afforded difficulty in delineating the role of each of its components, PNa and GFR, in regulating sodium excretion, largely because maneuvers designed to alter these components also tend to alter the filtered load in the same direction. The bulk of evidence, when subjected to critical review (2, 3), supports the view that acute changes in UNaV can be accounted for by fluctuations in filtered load.The present study examines the relationship between filtered load of sodium and UNNV when hypertonic saline and the simultaneous disproportionate depression of GFR.The results suggest that under these circumstances there is not a direct relationship between filtered load and UNMV, and that UNaV is in some manner related to PNa. METHODSThe experimental animals were anesthetized female mongrel dogs weighing 10 to 15 kg. The experiments were performed in the morning, and neither food nor water was restricted before the experiments. The animals were fed regular commercial kennel rations and were not sodium depleted. Anesthesia was produced with iv sodium pentobarbital (25 mg per kg body weight).Exogenous creatinine clearance was taken as a measure of GFR except in experiment 1, in which inulin clearance was used. Sustaining infusions of creatinine or inulin consisted of appropriate amounts of these substances in 0.9% saline infused in a foreleg vein at 1.0 ml per minute. At least 40 minutes was allowed for equilibration of the creatinine or inulin priming solutions. Urine was collected via an indwelling catheter. Completeness of collections was assured by rinsing the bladder with distilled water followed by rinsing with 100 ml of air at the end of each collection period. (Only air rinses were used in experiment 1.) The collection periods were 30 to 40 minutes long in most instances.Blood was taken at the mid-point of the urine collections from an inlying needle in a femoral artery.Creatinine was determined by the method of Knowlton (4) and inulin by the method of Walser, Davidson, and Orloff (5). Sodium determinations were made with a Baird internal-s...