H. E. Himwich

Effect of Metrazol Convulsions on Brain Metabolism.

The wide use of metrazol in the treatment of schizophrenia has made it advisable to study the physiological changes produced by metrazol convulsions. 1 Twelve observations were made on 7 patients with schizophrenia. As seen in Table I, 7 samples of blood were collected from the femoral artery during various stages of the convulsions, 4 pairs of samples were collected simultaneously by 2 observers from the femoral artery and internal jugular vein immediately after the seizure had ceased, as was one additional sample of arterial blood. Breathing was greatly diminished during the convulsions and this was reflected in the analyses of the arterial blood, which disclosed a retention of CO2 as well as a diminished O2 content. Even during the first part of the seizure, as seen in Wi, 9/13, the O2 content was diminished so that the Hb saturation was reduced from a theoretical normal of 95% to 84%. As the convulsions progress, the Hb saturation continues to fall so that towards the end of the seizure the saturation of Hb may be below 50% (M., 9/7). During these convulsions the patients face is at first a dark red color. When the convulsion is completed, the anoxemia is evidenced by a leaden cyanosis, Neyertheless, as soon as unimpeded breathing is reëstablished the Hb saturation, though still reduced, is found rapidly rising towards a normal value (last 5 observations of Table I). The anoxemia, as well as the severe muscular effort, combine to increase blood lactic acid and blood sugar. These convulsions, grand mal in character, cause a temporary but marked depression of cerebral functions as evidenced by amnesia, confusion, disorientation, and the elicitation of various abnormal reflexes, such as the Babinski and ankle clonus.

A review of hypoglycemia, its physiology and pathology, symptomatology and treatment

We have seen that it is important to maintain the level of blood sugar in our bodies because if it is reduced beyond the lower normal limits, the brain is deprived of its foodstuff, glucose. The relative danger of hypoglycemia may be measured by the methods which have been provided for their prevention. Only one mechanism — the parasympathetic-insulin apparatus — acts to limit arise in blood sugar, while the symptoms working against afail in blood sugar are many and intricate: the sympathetic-adrenalin apparatus, the thyroid and posterior pituitary, as well as the anterior pituitary and adrenal cortex. Hypoglycemia may arise from 3 general causes: (1) failure of the liver, (2) excessive insulin, and (3) a disturbance in the neuroendocrine defense. It has been shown that when hypoglycemia does arise, the symptoms are the same irrespective of the cause, and fall into a definite sequence of five stages. This sequence is ascribed to different metabolic rates in the various regions of the brain, the highest beingfound in the newest portions, and each succeeding part possessing a lower rate. Since the areas with the most intense metabolic rate will be the first to suffer upon withdrawal of energy, the earlier symptoms of hypoglycemia are allocated to the new phyletic layers, and each succeeding phase is localized according to the decreasing metabolic activity in the subcortical layers. Using these 5 stages as a guide, it is possible to prevent dangerous hypoglycemia by proper treatment upon recognition of the initial symptoms. An examination of the patient will reveal his stages of hypoglycemia, and carbohydrate administered at any time before the symptoms of the 5th phase last too long will insure immediate recovery. But any delay after that time will render the prognosis more and more precarious.

Effects of Cyanide and Iodoacetate on Survival Period of Infant Rats.

Summary The prolonged survival period of infant rats, despite inhibition of the cytochrome-oxidase system with sodium cyanide, demonstrates the function of an anaerobic source of energy. The rapid death after the injection of iodoacetic acid and exposure to an atmosphere of nitrogen suggests the anaerobic conversion of carbohydrate to lactic acid as the source of this energy.

Effect of Hypothermia on Cerebral Metabolism

Summary Nine dogs, subjected to hypothermia, suffered a decreased cerebral metabolism as indicated by a smaller A:V difference despite a slower blood flow.

Changes in Cerebral Blood Flow and Arterio-Venous Oxygen Difference During Insulin Hypoglycemia.∗

Previous work has disclosed that the arterio-venous oxygen difference of cerebral blood is diminished during insulin hypogly-cemia. 1 , 2 However, the arterio-venous oxygen difference is determined not only by the metabolic rate of the brain, but also by velocity of blood flow. Therefore, thd possibility exists that the smaller oxygen difference found may be due to a more rapid blood flow during hypoglycemia. Observations by Loman and Myerson 3 on human subjects and Leibel and Hall 4 on rabbits, have failed to demonstrate any marked changes in the rate of cerebral blood flow during insulin hypoglycemia uncomplicated by convulsions. However, for conclusive information regarding changes of brain metabolism, it is necessary to determine, simultaneously, the cerebral blood flow and the arterio-venous oxygen difference. The results of such a study on patients with schizophrenia are presented in this preliminary report. Methods for the collection and analysis of the blood samples have been previously described. 2 The rate of blood flow in the internal jugular vein was estimated by a modification of the Gibbs thermostromuhr. This instrument proved to be at least as sensitive as the original and will be described elsewhere. Observations on the blood flow were made over long periods during which the position of the thermostromuhr in the vein was maintained constant. A special technique was devised which prevented error resulting from the formation of clots on the needle. In 5 cases the blood flow and the arterio-venous differences were determined before injection of insulin as well as throughout the course of the coma and the subsequent administration of glucose. In 3 other instances the observations were begun during coma and continued until after arousal with intravenous glucose.

Effect of Cyanide on Cerebral Metabolism.

Summary and Conclusions The effects of intravenous and intracarotid cyanide injection on cerebral and muscle metabolism were studied; 37 observations were made on 11 dogs. A significant decrease in the cerebral oxygen consumption was observed, a decrease which varied directly with the concentration of cyanide used. The concentration of cyanide which depressed metabolism of brain failed to exert an effect on the arterial-venous difference of muscle blood. The significance of these findings is discussed.

Syndromes Secondary to Prolonged Hypoglycemia.

In an attempt to study the effects of prolonged hypoglycemia dogs and cats were injected with insulin and subjected to coma for varying periods. The duration of the coma was frequently extended as long as possible compatible with life. The symptomatology, which subsequently developed, occurred despite a blood sugar raised to normal levels or higher by the administration of sugar. The post hypoglycemic syndromes are characterized by their variability. For example, dog No. 4, which received insulin for 4 days and was intermittently in coma for approximately one-half of that time, became totally blind in his left eye and retained only light perception in his right one. He was continually moving about and in his aimless restlessness would bump into any object that might confront him. When food was placed in his mouth he showed no inclination to swallow it, but kept it there indefinitely. Another animal, cat No. 2, remained in a fixed position, an awkward one, standing on his hind legs and leaning upright against the side of the cage for at least 12 hours, though the blood sugar was raised to normal levels throughout this period. Cat No. 6 displayed the crossed extensor reflex and spasticity of the posterior extremities. In cats the temperature regulation is frequently impaired after prolonged hypoglycemia. Cat No. 3 became to a great extent poikilothermic. After recovery from a 7-hour period of hypoglycemia his temperature was only 36.6° despite torrid weather. The next morning his temperature was 38.7°, but after remaining in the ice room for 15 minutes his temperature fell to 38° and 20 minutes later to 36.3° with no shivering. Four hours after removal from the ice room the animals temperature rose to 39° and his response to temperature was not tested again.

Respiratory Quotient of Diabetic Liver

Summary Thirty-seven observations of the R.Q. of the liver of cats depancreatized 48-72 hr. revealed an average R.Q. of 0.59.

Effect of Neosynephrin∗ on Gaseous Exchange of the Brain.†:

The effects of neosynephrin on the cerebral arterio-venous oxygen difference were studied on large dogs, narcotized with Dial,† 0.5 cc per kilo. The cranium was trephined above the superior longitudinal sinus, the trachea was exposed and cannulated and both femoral arteries were also exposed. The first pair of femoral arterial and cerebral venous blood samples was collected while the animals were breathing air and the second after they had come to equilibrium while respiring a gas mixture containing approximately 11% oxygen. Neosynephrin was then administered and when blood pressure had risen significantly the third pair of blood samples was collected. Blood flow of the cerebral longitudinal sinus was determined by Dalys modification of the thermostromuhr. 1 Blood pressure was recorded by means of a cannula inserted into a femoral artery. Blood samples were analyzed for oxygen and carbon dioxide contents and oxygen capacity, 2 for glucose, 3 and for lactic acid. 4 The oxygen tension of the blood was estimated by using the nomogram of Bock et al. for humans 5 which may also be applied to dogs. 6 In addition, the effects of neosynephrin on the cerebral arteriovenous oxygen difference were determined on dogs breathing room air. In most experiments 2 cc of 1% neosynephrin solution were administered intramuscularly, portions of the 2 cc being injected at various sites. In a few experiments, however, 1-10,000 neosynephrin solution was injected intravenously and in these instances the amount of neosynephrin injected was much smaller than with intramuscular injection. In Table I are presented the results of 2 out of 4 experiments on animals breathing reduced concentrations of oxygen. In all 4 experiments the blood became more alkaline as a result of the hyperpnea produced by breathing 11% oxygen and then less alkaline after injections of neosynephrin. Neosynephrin increased the concentrations of lactic acid and glucose in the blood.

Chronic Adrenal Insufficiency and Pancreas Diabetes.

Grollman and Firor 1 have demonstrated that chronic adrenal insufficiency, induced by various methods, is primarily a disturbance of pituitary origin. The syndrome which follows, cessation of growth, failure of reproductive activity and subnormal body temperature is, according to the above workers, relieved by administration of pituitary extracts and not by cortin. Long 2 has shown that acute adrenal insufficiency caused by the removal of the adrenal gland, though accompanied by injections of cortin, ameliorates experimental pancreatic diabetes. The object of the present experiments is to determine the effects of chronic adrenal insufficiency on the course of experimental pancreatic diabetes. Eight cats were anesthetized with sodium pento1)arl)ital and both lumboadrenal veins were ligated distally and proximally to the gland. L4t the same time the entire pancreas was removed. The animals received neither insulin nor cortin. Fluid was given ad lib. along with a Lveighetl amount of food (Bovex) each day. The periods of survival were 11, 11, 12, 15, 17, 18, 20, and 98 days. The life span of these animals was definitely prolonged by the ligation, for depancreatized cats usually succumb before 8 days. At the present time we shall present a brief description of the cat which survived for 98 days. After the operation the cat exhibited a pro found glycosuria. hut 2 iveeks later the urine ivas free of sugar and remained so until death. There was a marked (501%) loss in body weight. - At autopsy careful examination revealed no traces of pancreatic tissue. The adrenal glands appeared degenerated. The kidney cortex Was ivhite due to increased deposition of fat, 14.8% on analysis, although the liver Ivas free of fatty infiltration and contained the normal amount of fat, 4.5%. Two large and several small ulcers were found on both sides of the pyloric orifice of the stomach.