The effect of adrenal denervation on the metabolic effects of hyperammonemia in sheep

The metabolic effect of intravenous infusion of ammonium chloride (60 μmol/(kg body weight∙min)) was compared in five sheep before and after adrenal denervation. Adrenal denervation completely abolished the hyperglycemic effect of ammonium chloride, diminished the rise of pyruvate and lactate concentration, and failed to influence the lipolytic effect of NH4Cl It is suggested that the metabolic effects of ammonia are in a different degree related to the action of ammonia on the central nervous system and (i) the hyperammonemic effect of ammonia completely depends on the neurogenic increase of adrenal medullary hormones; (ii) the rise of blood lactate and pyruvate level observed during hyperammonemia is only partially mediated by adrenaline; and (iii) the lipolytic effect of ammonia ion does not depend on the nerve-controlled secretion of adrenal medullary hormones.Key words: adrenal denervation, hyperammonemia, metabolism, sheep.

The Effects of Nimodipine on Cerebral Blood Flow and Metabolism

Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1–3.0 μg kg−1 min−1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.

Effect of Amytal on metabolism of perfused rat heart: relationship between glycolysis and oxidative phosphorylation

In perfused rat hearts, infusion of increasing concentration of Amytal caused progressive inhibition of respiration and increase in glycolytic activity. At maximal inhibition of respiration, with glucose as the substrate, glycolysis provided about 60% of the total ATP produced. The myocardial content of ATP remained constant irrespective of the infused Amytal concentration but [CrP]/[Cr] and [ATP]/[ADP]f[Pi] progressively decreased. Changes in the concentrations of glycolytic intermediates were observed, the most pronounced of which were increases in fructose 1,6-diphosphate and lactate contents and a decrease in the pyruvate level. Myocardial levels of oxaloacetate, malate, and alanine were elevated and so was alanine release from the tissue. Substitution of glucose with pyruvate caused a large increase in the concentrations of the tricarboxylic acid cycle intermediates and consequent accumulation of reducing equivalents in the mitochrondria. With the latter substrate, in the presence of Amytal, the rates of mitochondrial ATP production were higher than those with glucose as the substrate. The metabolic picture of the Amytal block resembles biochemical manifestations of human myopathies of mitochondrial origin, and therefore Amytal inhibition is a convenient model system for exploration of intermediary metabolism in these defects.

Computer simulation of metabolism in pyruvate-perfused rat heart. IV. Model behavior

The behavior of a computer model of energy metabolism was determined for perfused rat hearts utilizing pyruvate as sole exogenous fuel and subjected to a rapid increase in work load. Computer-generated metabolite profiles, which are solutions of the differential equations for 1 min elapsed time, closely match 12 experimental curves (involving 120 concentration measurements) and exhibit the following properties. The computed cytosolic pyruvate level oscillates due to large changes in the rates of the processes that produce and consume this metabolite. Cytosolic Mg2+ seems to act as a coordinated controller of glycolytic enzymes; its transient increase permits a transient increase of glycolysis without an accumulation of glucose 6-phosphate. Lactate is exported to the interstitium by a lactate permease and then reimported and oxidized. As a result, the malate-aspartate shuttle reverses direction, and the Krebs cycle is “unspanned.”

Cell wall composition and incorporation of radio-labelled compounds by Veillonella alcalescens

The cell wall of Veillonella alcalescens was shown to have a typically Gram-negative appearance and composition. The wall contains 24% lipid, 0.8% phosphorus, and 6.8% hexosamine. It is estimated to contain about 5% murein, unlike the 24% reported by other for Veillonella parvula. The amounts of 19 amino acids, including diaminopimelic acid, were determined. Though Veillonella sp. cannot metabolize sugars for energy, V. alcalescens incorporates ribose and fructose by separate, specific mechanisms and uses most of the incorporated sugar in nucleic acid synthesis. Large excesses of either sugar in the medium do not repress gluconeogenesis from the pyruvate level. We have been unable to detect phosphoglyceromutase (EC 2.7.5.3) by several assay methods but have no indication of a gluconeogenic pathway other than reverse glycolysis.

Activation of Pyruvate Dehydrogenase in Adipose Tissue: Role of Insulin and Pyruvate

This study was designed to investigate the relation between activation of pyruvate dehydrogenase in white adipose tissue and the intracellular pyruvate content. The intracellular pyruvate level was approximately 8 nmol/g wet weight when adipose tissue was incubated up to 20 min with fructose (1 mg/ml) as substrate. The addition of insulin to the incubation medium resulted in a 1.5-fold increase in the active form of pyruvate dehydrogenase after 20 min incubation without raising the intracellular pyruvate level at earlier time periods. Intracellular pyruvate contents were increased 1.5-fold by TMPD (75 μM), but in this case there was no concomitant activation of pyruvate dehydrogenase. We conclude that the insulin-induced activation of pyruvate dehydrogenase is caused by mechanism(s) in addition to an elevation of pyruvate concentration.

THE EFFECT OF ADRENALECTOMY ON BLOOD PYRUVATE IN CATS INJECTED WITH GLUCOSE AND INSULIN

SUMMARY Injection of glucose (290 mg./kg.) with insulin (0·5 unit/kg.) into conscious adrenalectomized cats was followed by an increase in venous pyruvate concentration which was not seen in intact cats given the same doses of glucose and insulin. When normal cats received 1·5 units insulin/kg. with the glucose there was again no sustained change in blood pyruvate concentration during the first 30 min. after injection. In these animals the decrease of blood glucose was the same as in the adrenalectomized cats, and greater than in intact cats injected with 0·5 unit insulin/kg. After glucose and insulin had been given to acutely eviscerated cats the blood pyruvate level rose in previously adrenalectomized animals and fell in previously intact animals. These results provide some support for an extrahepatic action of glucocorticoid hormones.