Aaron P. Sanders

Brain Adenosine Triphosphate: Decreased Concentration Precedes Convulsions

The concentration of adenosine triphosphate in the brain decreased before the onset of generalized convulsions in unanesthetized rats subjected to acute hypoxia or treated with hydroxylamine or pentylenetetrazole (Metrazol). As the convulsive episode continued, adenosine triphosphate decreased further. Stimulation of adenosine triphosphate production forestalled its disappearance from the brain and delayed the development of seizure activity.

Succinate: Protective Agent against Hyperbaric Oxygen Toxicity

When succinate is used to protect rats against the toxicity of oxygen at high pressure, 100 percent survive, with normal or above normal concentrations of adenosine triphosphate being present in the cerebral hemisphere, liver, and kidney. In contrast, 90 percent of the nonprotected animals died during exposure. In corresponding tissues of surviving nonprotected animals adenosine triphosphate concentrations are markedly reduced.

The Evaluation of Pancreatic Function by Use of I131 Labeled Fat

Summary A study using an I 131 labeled fat meal has been carried out on 30 patients with proven pancreatic disease. Measurements were made of the per cent of blood radioactivity at four, five, and six hours following the test meal, and on a subsequent 48-hour collection of feces. The test yielded information of diagnostic value in 10 of 12 patients found to have chronic relapsing pancreatitis, in 17 of 18 patients with pancreatic carcinoma. In the absence of small bowel disease, pyloric obstruction, or gastric surgery, an impairment of fat absorption using this technique is strongly suggestive of pancreatic disease. The method can further be used as a laboratory aid in evaluating substitution therapy in patients with pancreatic insufficiency.

I131 blood levels correlated with gastric emptying determined radiographically. I. Protein test meal.

Conclusions 1. A characteristic and reproducible curve of radioisotope blood levels was obtained in normal humans and normal dogs following an I131 labeled protein test meal. 2. Radiographic determination of gastric emptying is necessary for the proper interpretation of data. 3. Delayed gastric emptying significantly altered the radioisotope blood levels. 4. Fainting and change in position may alter radioisotope blood levels.

Fat Absorption from the Human Gastrointestinal Tract in Patients Undergoing Radiation Therapy

The effect of ionizing radiation on the gastrointestinal tract was first noted by Walsh in 1897 (1). The circumstances under which the irradiation was given and the amount are unrecorded. Since that time, many studies as to the effect of radiation on the digestive tract have been carried out. These have been directed toward a morbid anatomical evaluation or a physiological evaluation, or both. Excellent studies of the anatomical changes in the small bowel after irradiation in varying amounts may be found in papers by Warren (2, 3), Martin (4), and Senn (5). Their observations have been substantiated by many other workers. The changes have consisted primarily of a loss of the intestinal epithelium, beginning with that in the crypts and progressing to the villi. Ulcerations then appear, extending through the submucosa and sometimes into the serosa. The extent of these lesions and the rapidity with which the process develops depend to a large extent upon the tissue dose received by the area. It has also been...

Effects of Hyperbaric Oxygenation on Metabolism I. ATP Concentration in Rat Brain, Liver and Kidney.

Summary 1) Tissue ATP concentrations were determined in the cerebral hemispheres, liver and kidney in rats exposed to air at 1 atmosphere, and to 100% oxygen for 2 hours at 1 and 3 atmospheres, and 1 1/2 hours at 5 atmospheres. 2 Liver and kidney had normal ATP levels at 1 atmosphere and increased ATP levels at 3 atmospheres (39% and 18% respectively). 3 Cerebral hemispheres had markedly depressed ATP concentrations at 1 atmosphere (57%) and 3 atmospheres (34%). 4 Significant decreases in ATP levels occurred in cerebral hemisphere (54%), liver (44%), and kidney (63%) of rats exposed to 100% oxygen for 1 1/2 hours at 5 atmospheres. 5 The significance of the findings is discussed.

RADIOISOTOPE-DILUTION CURVES AS AN ADJUNCT TO CARDIAC CATHETERIZATION.

Abstract A method of recordin externally monitored radioisotope-dilution curves at cardiac catheterization has been described. It was found to be reliable and had marked practical value as a routine procedure in the detection and localization of the site of left to right shunts. The geometry of the detection system was defined and correlated with the anatomic structures viewed by the heart and lung probes. Standards for normal curves were established in a series of patients without shunts. Radioisotope curves were compared with arterial dye-dilution curves and blood oxygen data for the detection and localization of the site of left to right shunts. All three methods detected shunts which comprised greater than 25 per cent of total pulmonary blood flow. The isotope and dye methods were found to be equally sensitive in the detection of small shunts if the indicator was injected into the pulmonary artery. All shunts detected by arterial dye-dilution curves were also detected by radioisotope-dilution curves. The reliability of the method was established and its practical usefulness shown. The major advantages of the radioisotope technic without blood sampling were found in severely ill young infants in whom the technic provided a quick and reliable method for the detection and localization of the site of the shunt.

Protection of brain metabolism with glutathione, glutamate, gamma-aminobutyrate and succinate.

Studies on protective agents in oxygen toxicity experiments led us to believe that a glutathione (GSH)-glutamate-γ-aminobutyrate (GABA)-succinate pathway may serve as a secondary support system in the maintenance of brain energy levels (adenosine triphosphate [ATP] concentration). This “shunt” is shown in Fig. 1. The glutamate-GABA-succinicsemialdehyde-succinate shunt is a well established pathway (1-8) to which no major physiological significance has been attached. The GABA-succinate shunt has been suggested as a means of metabolizing GABA (9, 10). It has also been reported to function as a means of bypassing inhibition of the alpha-ketoglutarate dehydrogenase system of the citric acid cycle by withdrawal of alpha-ketoglutarate from the cycle by transamination with GABA to yield glutamate and reentry of the carbon chain of GABA into the cycle at the succinate level (9, 10). The possible physiological importance of the shunt is seen if one recognizes that succinate markedly stimulates respiration and oxidative phosphorylation. Krebs et al. (11) reported that succinate oxidation can monopolize the respiratory-electron transport chain which is the major source of ATP production. Sanders et al. (12, 13) observed significantly higher respiration rates with succinate in brain, liver, and kidney of rats when compared with alpha-ketoglutarate and glutamate. Data shown later indicate that succinate stimulates brain respiration and oxidative phosphorylation in the mouse, rat, guinea pig, rabbit, cat and dog. The factor limiting the amount of succinate available for metabolism has generally been considered to be the rate at which alpha-ketoglutarate is converted to succinate by enzymes of the Krebs cycle. Roberts (8) showed that conversion of GABA to succinate by GABA transaminase is rapid, and that both glutamic acid decarboxylase and GABA transaminase have pH optima (6.5 and 8.2, respectively) such that small changes in intracellular pH—within the physiological range—could result in large changes in these enzyme activities in situ (8, 14, 15).

Effects of Hyperbaric Oxygenation on Metabolism III. Succinic Dehydrogenase, Acid Phosphatase, Cathepsin and Soluble Nitrogen.

Summary 1. Succinic dehydrogenase, ca-thepsin and acid phosphatase activities and soluble and total nitrogen were determined in homogenates of the cerebral hemispheres, liver and kidney from rats previously exposed to normal air, and 100% oxygen for 2 hours at 1 and 3 atmospheres, and for 11/2 hours at 5 atmospheres. 2. HPO caused a decrease of succinic dehydrogenase activity and an increase in free lysosomal enzymatic activities with increasing pressure. 3. There was a slight decrease in percent soluble nitrogen at 1 and 3 atmospheres, and a marked increase at 5 atmospheres. 4. Increased free lysosomal enzyme activities and subsequent solubilization of protein structures are major destructive factors in high pressure oxygen toxicity.

Use of I131 Labeled Oleic Acid in Study of Gastrointestinal Function.

Summary and Conclusion 1. Constant and reproducible curves of blood radioactivity levels are found in normal humans and dogs after an oleic acid test. 2. Following pancreatectomy and induced pancreatitis in dogs, the curves obtained with oleic acid test were within normal range while those obtained with triolein were depressed.