THE EFFICIENCY OF VARIOUS DIURETICS IN THE ACUTELY NEPHROPATHIC KIDNEY, PROTECTED AND UNPROTECTED BY SODIUM CARBONATE. II.
The outline which has been given of the relative toxicity of Gréhant's anesthetic in normal animals, in animals that were nephropathic from uranium and protected against the anesthetic by an alkaline solution, and in those animals which were unprotected by such a solution, furnishes the basis for the following summary. The kidney of the normal dog is relatively non-susceptible to the toxic action of Gréhant's anesthetic. The kidneys have failed to show any change in their histological structure during the period of anesthesia. These animals have remained diuretic during the period of anesthesia and have responded to diuretics such as theobromine, pituitrin, and solutions of urea and sodium chloride. Normal animals anesthetized with Gréhant's mixture for 1(1/2) hours usually show at the end of the experiment either no change, or only a slight variation from the normal, in the hydrogen ion content of the blood, the alkali reserve of the blood, and in the tension of carbon dioxide. In several normal dogs which were over 4 years of age, by the end of an anesthesia of such a duration the animals have shown a reduction in the alkali reserve of the blood and also a decrease from the normal in the carbon dioxide tension of alveolar air. From this observation it would appear that even in a normal animal Gréhant's anesthetic tends to induce an acid intoxication, and as was the case with normal animals which were being intoxicated by uranium, such an intoxication is more readily induced in an old animal than in a young one. The nephropathic animals which have been anesthetized by Gréhant's anesthetic and in which an attempt has been made to protect these animals against the toxic effect of the anesthetic by the use of asolution of sodium carbonate fall into two clear-cut groups. Those animals of the series not over 1(1/2) years old have shown at the end of the uranium intoxication and prior to the use of the anesthetic a less severe acid intoxication than have the animals of the series which were over 1(1/2) years old. In this younger group of animals the intravenous injection of a 3 per cent solution of sodium carbonate immediately before the animals were anesthetized has succeeded in protecting these animals against the toxic action of the anesthetic. During the following 1(1/2) hours of anesthetization these animals have not developed a severe grade of acid intoxication, and in several of the animals at the end of the experiment the alkali reserve of the blood was in excess of what it was at the end of the uranium intoxication and before an anesthetic was administered. Animals of this protected group have remained diuretic throughout the experiment and have shown an active diuresis from pituitrin, theobromine, and solutions of urea and sodium chloride. The kidneys of such animals have shown histologically a normal vascular tissue, a convoluted tubule epithelium which gave the appearance of being hyperactive, and only occasionally were tubules encountered which showed signs of an early epithelial degeneration. The nephropathic animals of the series in which a solution of sodium carbonate failed to afford any protection against Gréhant's anesthetic were animals over 1(1/2) years old in which the uranium intoxication had resulted in a severer grade of add intoxication than in the younger animals. When these older animals were given intravenously the carbonate solution and were anesthetized, it was found impossible to increase the alkali reserve of the blood to the same extent as was possible in the younger animals. Furthermore, the alkaline solution during the period of anesthesia is rapidly used up so that by the termination of these experiments the animals may have an alkali reserve of the blood which may be even lower than was the alkali reserve before the use of the carbonate. These animals have remained completely anuric throughout the experiments and have shown no diuretic effect from those diuretics which in the animals that were successfully protected by the carbonate induced free diuresis. The kidneys of these anuric animals show no degenerative changes in the glomerular vessels. The capillaries are not distended with blood as has been the case with the diuretic group. The epithelium of the convoluted tubules is acutely swollen. The swelling has frequently taken place to such an extent that the lumen of the tubules has become obliterated. The nephropathic animals of the series which served as control animals and which were given a solution of sodium chloride equimolecular with the carbonate solution, following Gréhant's anesthetic became completely anuric. The sodium chloride solution furnished no protection against the anesthetic. The animals of all ages became anuric and unresponsive to the diuretic substances which have been used during this study. With the establishment of a state of anuria in these control animals the hydrogen ion content of the blood has increased, the alkali reserve of the blood has been rapidly depleted, and associated with this change the carbon dioxide tension has been reduced. The rapidity with which these changes develop and the degree of acid intoxication which is induced is more marked in these animals than in any of the other series. The kidneys of the control animals show the severest grade of degeneration of any of the nephropathic animals. The epithelium of the convoluted tubules is not only severely swollen but the cells frequently show necrosis. The loops of Henle contain more stainable fat than has been demonstrated in the kidneys of the carbonate animals.
Macnider
W D
WD
Laboratory of Pharmacology of the University of North Carolina, Chapel Hill.