Mode Of Infusion Research Articles

Sustained water diuresis in anesthetized dogs: antidiuresis in response to intravenous and bilateral intracarotid infusion of hyper-osmolar solutions of sodium chloride.

AbstractThe function of the suggested hypothalamic osmoreceptors was re‐examined in dogs during light chloralose anesthesia. The body weight of the dogs was increased to—and maintained at—102.0% of the initial value by i.v. infusion of a hypo‐osmolar solution of glucose and urea. During the water diuresis renal free water clearance (CH2O) remained approximately constant for more than 3 h during which infusion of physiological amounts of vasopressin (5 or 10 μU/(kg b.wt. · min)) was associated with a dose‐dependent, reversible decrease in CH2O. Infusion of hyper‐osmolar sodium chloride solution (90μmol/(kg b.wt. · min) for 60min) was performed either through a central venous catheter or through needles placed in both common carotid arteries. After an initial increase in CH2O these infusions elicited antidiuresis (negative CH2O) and increase in the rates of excretion of sodium (100‐fold) and potassium (3‐fold). Left atrial pressure and renal clearance of inulin and PAH did not change significantly. The renal effects of NaCl infusion were independent of the mode of infusion. It is concluded that the results are inconsistent with the hypothesis that the area supplied by the common carotid arteries includes an osmoreceptor which is capable of changing —within seconds—the rate of secretion of vasopressin, although they support the view that the renal excretion of water is strongly influenced by a receptor which is sensitive to osmolality or concentration of sodium. In addition it appeared that an increase of a few per cent in the concentration of sodium in plasma was associated with a substantial increase in the rate of excretion of sodium without measurable changes in central venous pressure or in glomerular filtration rate.

Studies on the Percutaneous Absorption of Parathion and Paraoxon. V. Rate of Absorption of Paraoxon

One way to determine rate of percutaneous absorption is dose-response comparisofts following this mode of administration and intravenous infusion. This method has been discussed in detail by Fredriksson (1) and Griesemer et al. (2) in connection with measurements- of the rate of absorption of an organophosphorus cholinesterase inhibitor, sarin. The last-mentioned authors chose inhibition of blood cholinesterase activity in the rabbit as a basis for the dose-response comparison. It was decided to use the same parameter in connection with the two routes of administration in order to determine the rate of percutaneous absorption of paraoxon, a compound that belongs to the same pharmacologic group as sarin, but to modify the technic in several respects in order to improve the accuracy. Thus, the cat was selected as experimental animal, since this species has higher plasma cholinesterase activity than the rabbit. A higher activity makes the individual determinations of enzyme activity more accurate. Furthermore, it was decided to adjust the rate of infusion so that it corresponded as closely as possible to the rate of percutaneous absorption, since the distribution of organophosphorus compounds, their detoxification and, thus, the proportion available for enzyme inhibition is dependent on the rate of systemic administration (see review by Holmstedt, 3). Since there obviously must be a latency period before the topically applied material will reach the blood stream and produce inhibition of the enzyme activity, an adjustment of the rate of infusion so that the degree of enzyme inhibition after a given interval is the same as the degree of inhibition after the same interval following percutaneous application by necessity must result in too low values concerning the rate of percutaneous absorption. This potential error may be increased also if single measurements of enzyme activity are used because of their relative inaccuracy. Therefore, it was decided to adjust the rate of infusion so that the rate of enzyme inhibition was the same as following topical application. This makes corrections for the hypothetical latency period unnecessary, and the slope of the inhibition curve, determined by several measurements of activity, can be used as basis for the comparison instead of single and, therefore, uncertain activity values. Finally, in order to diminish errors due to variations in blood volume and, thus, absolute amount of enzymes present it was decided to use animals of as uniform weight as the stock permitted.