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Biomedical subjects

T E Duffy

Publications and source records attributed to T E Duffy.

At least 37 records · Page 2Linked to original sources
PubMed1980

A mask for delivery of inhalation gases to small laboratory animals.

A mask was developed for the administration of volatile anesthetics and other gases to small, spontaneously breathing laboratory animals. A vacuum-powered venting system surrounding the inspiratory gas supply prevented potentially hazardous gases from escaping into the environment. This system was used to deliver nitrous oxide, halothane, and methoxyflurane to rats, gerbils, and newborn dogs. It was used to vary the oxygen and carbon dioxide concentrations inspired by spontaneously breathing animals undergoing physiological experiments.

Anesthesia, Inhalation↗
PubMed1979

The metabolic fate of 13N-labeled ammonia in rat brain.

13N-labeled ammonia was used to study the cerebral uptake and metabolism of ammonia in conscious rats. After infusion of physiological concentrations of [13N]ammonia for 10 min via one internal carotid artery, the relative specific activities of glutamate, glutamine (alpha-amino), and glutamine (amide) in brain were approximately 1:5:400, respectively. The data are consistent with the concept that ammonia, entering the brain from the blood, is metabolized in a small pool of glutamate that is both rapidly turning over and distinct from a larger tissue glutamate pool (Berl, S., Takagaki, G., Clarke, D.D., and Waelsch, H. (1962) J. Biol. Chem. 237, 2562-2569). Analysis of 13N-metabolites, after infusion of [13N]ammonia into one lateral cerebral ventricle, indicated that ammonia entering the brain from the cerebrospinal fluid is also metabolized in a small glutamate pool. Pretreatment of rats with methionine sulfoximine led to a decrease in the label present in brain glutamine (amide) following carotid artery infusion of [13N]ammonia. On the other hand, 13N activity in brain glutamate was greater than that in the alpha-amino group of glutamine, i.e. following methionine sulfoximine treatment the expected precursor-product relationship was observed, indicating that the two pools of glutamate in the brain were no longer metabolically distinct. The amount of label recovered in the right cerebral hemisphere, 5 s after a rapid bolus injection of [13N]ammonia via the right common carotid artery, was found to be independent of ammonia concentration within the bolus over a 1000-fold range. This finding indicates that ammonia enters the brain from the blood largely by diffusion. In normal rats that were killed by a freeze-blowing technique 5 s after injection of an [13N]ammonia bolus, approximately 60% of the label recovered in brain had already been incorporated into glutamine, indicating that the t1/2 for conversion of ammonia to glutamine in the small pool is in the range of 1 to 3 s or less. The data emphasize the importance of the small pool glutamine synthetase as a metabolic trap for the detoxification of blood-borne and endogenously produced brain ammonia. The possibility that the astrocytes represent the anatomical site of the small pool is considered.

Ammonia↗
PubMed1979

Local cerebral glucose metabolism during controlled hypoxemia in rats.

2-Deoxy-[14C]glucose metabolism was examined in brains of hypoxic, normotensive rats by autoradiography, which revealed alternating cortical columns of high and low metabolism. Activity in white matter was increased severalfold over that in adjacent gray matter. The columns were anatomically related to penetrating cortical arteries with areas between arteries demonstrating higher rates of metabolism. The results suggest the presence of interarterial tissue oxygen gradients that influence regional glucose metabolism. The relatively greater sensitivity of white matter metabolism to hypoxia may lead to an understanding of white matter damage in postanoxic leukoencephalopathy.

Animals↗
PubMed1979

The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.

The cyclotron-produced radionuclide, 13N, was used to label ammonia and to study its metabolism in a group of 5 normal subjects and 17 patients with liver disease, including 5 with portacaval shunts and 11 with encephalopathy. Arterial ammonia levels were 52-264 micron. The rate of ammonia clearance from the vascular compartment (metabolism) was a linear function of its arterial concentration: mumol/min = 4.71 [NH3]a + 3.76, r = +0.85, P less than 0.005. Quantitative body scans showed that 7.4 +/- 0.3% of the isotope was metabolized by the brain. The brain ammonia utilization rate, calculated from brain and blood activities, was a function of the arterial ammonia concentration: mumol/min per whole brain = 0.375 [NH3]a - 3.6, r = +0.93, P less than 0.005. Assuming that cerebral blood flow and brain weights were normal, 47 +/- 3% of the ammonia was extracted from arterial blood during a single pass through the normal brains. Ammonia uptake was greatest in gray matter. The ammonia utilization reaction(s) appears to take place in a compartment, perhaps in astrocytes, that includes less than 20% of all brain ammonia. In the 11 nonencephalopathic subjects the [NH3]a was 100 +/- 8 micron and the brain ammonia utilization rate was 32 +/- 3 mumol/min per whole brain; in the 11 encephalopathic subjects these were respectively elevated to 149 +/- 18 micron (P less than 0.01), and 53 +/- 7 mumol/min per whole brain (P less than 0.01). In normal subjects, approximately equal to 50% of the arterial ammonia was metabolized by skeletal muscle. In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification. Muscle atrophy may thereby contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.

Adolescent↗
PubMed1978

Cerebral blood flow and metabolism in chronically hyperammonemic rats: effect of an acute ammonia challenge.

The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham-operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 +/- 5 (mean +/- SEM) to 139 +/- 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight-week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high-voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight-week portacaval rats, the only animals to show a net uptake of ammonia into brain. The findings suggest that increased cerebral sensitivity to ammonia, along with nonspecific effects of chronic portal-systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.

Ammonia↗
PubMed1977

Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts.

Rats were made chronically hyperammonemic by portal-systemic shunting and, 8 wk later, were subjected to acute ammonia intoxication by the intraperitoneal injection of 5.2 mmol/kg of ammonium acetate. In free-ranging animals, ammonia treatment induced a brief period of precoma (10-15 min) that progressed into deep, anesthetic coma lasting for several hours and was associated with a high mortality. In paralyzed, artificially ventilated animals that were lightly anesthetized with nitrous oxide, acute ammonia intoxication caused major disturbances of cerebral carbohydrate, amino acid, and energy metabolism that correlated in time with the change in functional state. At 10 min after injection (precoma), the concentrations of most glycolytic intermediates were increased, as was the lactate/pyruvate ratio. Citrate declined, despite a twofold rise in pyruvate, suggesting that the conversion of pyruvate to citrate had been impaired. Concentrations of phosphocreatine, and of the putative neurotransmitters, glutamate and aspartate, declined during precoma, but the concentrations of the adenine nucleotides in the cerebral hemispheres, cerebellum, and brain stem remained within normal limits. At 60 min after injection (coma), ATP declined in all regions of brain; the reduction in total high-energy phosphates was most notable in the brain stem. The findings indicate that cerebral dysfunction in chronic, relapsing ammonia intoxication is not due to primary energy failure. Rather, it is suggested that ammonia-induced depletion of glutamic and aspartic acids, and inhibition of the malate-asparate hydrogen shuttle are the dominant neurochemical lesions.

Adenosine Diphosphate↗
PubMed1976

Status epilepticus in immature rats. Protective effects of glucose on survival and brain development.

The role of glucose metabolism in alleviating the complications of status epilepticus (SE) was investigated in developing rats. Pretreatment with glucose reduced mortality from SE by 90% in rats under 1 week of age, 80% in 10-day-old rats, 50% in 15- to 20-day-olds, and not at all in adults. In 4-day-old animals, brain DNA synthesis during seizures, and in survivors, brain weight, DNA, RNA, protein, and cholesterol contents at 7 days of age were reduced less in glucose-treated than in saline-treated littermates. In the saline group, seizures caused a progressive fall in brain glucose level but no fall in blood glucose level, suggesting that glucose transport from blood to brain could not keep pace with glycolytic demands. In glucose-treated rats, blood and brain glucose concentrations remained elevated throughout the convulsive period. There was no reduction of brain adenosine triphosphate levels in either group. Thus, the protection by glucose appears to be related to its roles as a carbon source rather than an energy source. It is concluded that in immature animals, depletion of brain glucose can occur in the absence of hypoglycemia, and may be an important and potentially treatable complication of status epilepticus.

Adenosine Triphosphate↗
PubMed1976

Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery.

Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.

Adenosine Triphosphate↗