W. W. Swingle

Induction of Diabetes Insipidus in Adrenalectomized Dogs with Cortisone.

Summary High cortisone dosage in ad-renalectomized dogs induces marked polyuria and polydipsia. The 24-hour urine volume may exceed control values by 5-10 fold. The daily renal excretion of Na, Cl, and K is increased, but considering the quantity of water eliminated, the urine is very dilute. Pituitrin is effective in controlling the polyuria and polydipsia only when administered in large amounts. The normal water balance was not re-established until long after cortisone injections were discontinued.

On the Cortical Hormone of the Adrenal Gland.

The crude lipid extract of beef adrenal cortex 1 and the aqueous extract 2 obtained from the active lipid fraction contain, with the cortical hormone, small quantities of adrenalin. The adrenalin content of the aqueous extract is sufficiently low to permit the demonstration of its efficacy in maintaining indefinitely the lives of adrenalectomized cats. 2 , 3 A simple method for the separation of adrenalin from the cortical hormone has been found. 4 The 70% alcohol soluble fraction obtained by our previously described method 2 is transferred to 95% alcohol and filtered through permutit. An extract with an adrenalin concentration of less than 1:2,000,000 (bio-assay-blood pressure) and a tissue equivalent of 30 gm. of cortex per cubic centimeter can be prepared by filtering through permutit twice using 20 gm. per kilo of tissue on the first filtration and 10 gm. per kilo on the second. The active material remaining in the permutit filter after each filtration is washed out with alcohol. The active fraction is transferred to water and the extract clarified by Seitz filtration. Besides adrenalin the permutit removes most of the contaminating pigment substances along with other inert material. Intravenous injections of this type of extract have been used successfully in the crises of Addisons disease. 5 Fractionation with permutit has made possible the preparation of active extracts from whole beef adrenal glands thereby doing away with the expense of dissection. These extracts have been found to be just as active in restoring prostrate adrenalectomized cats to apparently normal health as extracts prepared from dissected adrenal cortex. Whole adrenal gland extract (1 cc. equivalent to 50 gm. of whole gland) has an adrenalin content of approximately 1:2,500,000. This extract has been found suitable for subcutaneous, intraperitoneal and intravenous use. The solid content ranges in different batches from 0.3 to 0.4%.

Adrenal Insufficiency in Dogs with Normal Serum Na and CL

Summary A group of 5 adrenalectomized dogs of a large series studied, developed typical signs and symptoms of adrenal insufficiency in the absence of noteworthy alterations in the serum Na and CI values. Hypoglycemia was not present in any of the animals but during insufficiency dehydration and hemoconcentration were evident in 3 of them as indicated by marked increases in hemoglobin. In view of the inspissation of the blood in these dogs it seemed probable that sufficient water was not available for elimination of the electrolytes. This is the interpretation originally given by Nicholson and Soffer(4) to account for the death of their salt-injected dogs. However, a comparison of the hemoglobin concentrations of 8 adrenalectomized dogs exhibiting insufficiency with hyponatriemia (avg. 128 mEq/1) with the hemoglobin increases shown by the 5 animals discussed here, reveals that the hemoconcentration as gauged by hemoglobin changes was not more severe in the latter group. It is unfortunate that plasma volume determinations were not made. However, the drastic decline in arterial pressure and evident weakness of the animals indicated that defective functioning of the vasomotor system was probably the immediate cause of the symptoms. The hyperkaliemia of one dog was of sufficient magnitude to induce cardiac symptoms. The retention of a normal serum electrolyte pattern during insufficiency in these few exceptional dogs is reminiscent of the condition normally occurring in adrenal insufficiency in such animals as the opossum, marmot hamster (13) and certain elasmobranchs.

Effect of Intravenous Injections of Desoxycorticosterone Glucoside upon Blood Glucose of Adrenalectomized Dogs.

Summary and Conclusion (A) Three types of fasted adrenalectomized dogs were studied: (1) those maintained in normal health; (2) those exhibiting mild insufficiency symptoms; and (3) animals in severe adrenal crisis. When these dogs were injected intravenously with massive doses of DCG, only occasional blood glucose changes were observed. These infrequent rises in glucose were associated with marked improvement in the circulation of the animal, increased hydration, increased vigor and muscular activity. (B) A fasted, intact dog, injected with 300 mg DCG, did not show any significant changes in blood sugar level over a 24-hour period

Protection Afforded by Aqueous-Alcohol Solutions of Cortisone Against Dextran.

Summary Intramuscular injections of a soluble cortisone are much superior to the microcrystalline suspensions commercially available in affording protection to the 24-hour adrenalectomized rat infused with dextran. The amount of the soluble steroid required to give adequate protection is 30 times less than that found necessary when the suspension is used and the requisite time for prophylactic fore-treatment is reduced from 5 days to 6 hours. The procedure employed in these experiments can be utilized as the basis for a simple screening test for compounds with cortisone-like activity.

Some Factors Involved in the Assay of Renin

Summary The magnitude of the blood pressure rises given by large doses of renin must be corrected for differences in starting pressure levels, while those given by smaller doses need not be. An assay based on repeated tests on 2 or 3 dogs is as reliable as one based on a larger series of animals. Nembutal anesthesia may affect, in some dogs, the magnitude of the rise after large renin doses, but usually has little effect on the rise after small doses. For most routine testing, the anesthetized dog is the preferable test animal.