Increase of guanidine compounds in eclampsia: An experimental study

Abstract 1. 1. Several investigators have now demonstrated various biochemical or metabolic disturbances in eclampsia, such as fluctuations in blood sugar during the attack, and a trend toward hypoglycemic levels. Increase in blood uric acid and lactic acid, increase in blood pressure, edema, albuminuria, and convulsions are commonplace symptoms. 2. 2. Reports have been made of an increase in guanidine-like substances in the blood during preeclampsia and eclampsia. 3. 3. By experimental administration of guanidine compounds to animals all of the foregoing clinical symptoms of eclampsia may be reproduced, including the fluctuations in blood sugar and typical convulsive seizures. Moreover, the clinical use of certain guanidine compounds in reducing blood sugar levels in diabetics, as a substitute for insulin, has now been abandoned because of its toxic effects and its tendency to cause sudden and profound hypoglycemia. 4. 4. Authorities have differed as to whether the increased apparent guanidinemia in instances of acute liver injury, either clinical or experimental, precedes and causes the liver tissue degeneration, or follows it having resulted from this tissue destruction. 5. 5. The experimental injection of a single dose or two of a guanidine compound sufficient to kill an animal quickly should not be expected by an investigator to produce much if any histologic changes in the tissues of liver and kidneys, because of the abruptness of its action. 6. 6. This experimental investigation was undertaken to determine whether or not a more or less protracted series of guanidine and dimethyl guanidine injections would, by their cumulative action, cause histopathologic changes in the liver and kidneys. 7. 7. Degenerative changes of varying types but chiefly suggestive of early stages of hepatic degeneration have been produced in a large, controlled series of animals. These changes include cloudy swelling, interstitial hemorrhage, beginning periportal thrombosis, and fatty degeneration and infiltration both peripheral and central, as well as focal necroses similarly distributed. The kidneys showed cloudy swelling of the convoluted tubules, desquamation of lining cells, and hemorrhage. 8. 8. These hepatic changes were less distinctive in the animals to which guanidine injections were given by single daily doses than in those receiving the injections at hourly intervals to the point of death in one day. In the former, liver cell regeneration probably takes place during the resting period. It was, for example, by the latter method that the 6 animals (Group III) were treated, of which one showed the focal necroses in the liver referred to in the preceding paragraph. 9. 9. It is of interest that experimental administration of a metabolic toxin which can be elaborated within the body can reproduce in animals the major clinical symptoms and at least the early stages of the histopathologic changes seen in eclampsia. 10. 10. The exact source of an accumulation of guanidine-like substances within the body is still uncertain, and their relation to eclampsia is entirely problematic. 11. 11. Tables detailing the pathologic findings in this series of experiments are given, and numerous photomicrographs of liver and kidneys are shown.