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Biomedical subjects

R G Shulman

Publications and source records attributed to R G Shulman.

At least 163 records · Page 9Linked to original sources
PubMed1985

Cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy.

We determined cerebral intracellular pH in living rabbits and rats under physiologic conditions, using phosphorus NMR spectroscopy and new titration curves thought to be appropriate for brain. Mean values for the two species were, respectively, 7.14 +/- 0.04 (SD) and 7.13 +/- 0.03. These are toward the alkaline end of the range of values obtained by other methods, as values reported by other NMR workers also tend to be.

Animals↗
PubMed1985

Carbon-13 and phosphorus-31 nuclear magnetic resonance studies of myocardial metabolism in live guinea pigs.

Myocardial metabolism in live guinea pigs was investigated by 13C and 31P nuclear magnetic resonance (NMR) at 20.18 and 32.5 MHz, respectively. 13C NMR studies allowed monitoring of myocardial glycogen synthesis during intravenous infusion of D-[1-13C]glucose and insulin. Anoxia resulted in degradation of the labeled glycogen within 6 min and appearance of 13C label in lactic acid. Infusion of sodium [2-13C]acetate resulted in incorporation of label into the C-4, C-2, and C-3 positions of glutamate, reflecting "scrambling" of the label expected from tricarboxylic-acid-cycle activity. 31P NMR spectra of heart in live guinea pigs were obtained continuously in 20.5-sec time blocks during 3 min of anoxia, during subsequent reoxygenation, and, in separate animals, during terminal anoxia. Reversible anoxia resulted in rapid degradation of phosphocreatine (t1/2 = 54.5 +/- 2.5 sec), which recovered fully during reoxygenation. Heart inorganic phosphate increased during anoxia and returned to basal levels after oxygen was restored. During 3 min of anoxia, no significant changes in ATP levels or pH were detected.

Adenosine Triphosphate↗
PubMed1984

Carbon-13 nuclear magnetic resonance studies of myocardial glycogen metabolism in live guinea pigs.

Myocardial glycogen metabolism was studied in live guinea pigs by 13C NMR at 20.19 MHz. Open-chest surgery was used to expose the heart, which was then positioned within a solenoidal radio frequency coil for NMR measurements. The time course of myocardial glycogen synthesis during 1-h infusions of 0.5 g of D-[1-13C]glucose (and insulin) into the jugular vein was investigated. The possible turnover of the 13C-labeled glycogen was also studied in vivo by following the labeled glucose infusion with a similar infusion of unlabeled glucose. The degree of 13C enrichment of the C-1 glycogen carbons during these infusions was measured in heart extracts by 1H NMR at 360 MHz. High-quality proton-decoupled 13C NMR spectra of the labeled C-1 carbons of myocardial glycogen in vivo were obtained in 1 min of data accumulation. This time resolution allowed measurement of the time course of glycogenolysis of the 13C-labeled glycogen during anoxia by 13C NMR in vivo. With the solenoidal coil used for 13C NMR, the spin-lattice relaxation time of the labeled C-1 carbons of myocardial glycogen could be measured in vivo. For a comparison, spin-lattice relaxation times of heart glycogen were measured in vitro at 90.55 MHz. Natural abundance 13C NMR studies of the quantitative hydrolysis of extracted heart glycogen in vitro at 90.55 MHz showed that virtually all the carbons in heart glycogen contribute to the 13C NMR signals. The same result was obtained in 13C NMR studies of glycogen hydrolysis in excised guinea pig heart.

Animals↗
PubMed1984

In vivo phosphorus nuclear magnetic resonance spectroscopy in status epilepticus.

Bicuculline-induced status epilepticus was studied in paralyzed rabbits ventilated with an oxygen and nitrous oxide mixture. An Oxford Instruments TMR 32-200 spectrometer was used to record phosphorus 31 nuclear magnetic resonance spectra of the in vivo brain. An array of conventional physiological variables including the electroencephalogram was simultaneously recorded. Several features were consistently observed during status epilepticus: (1) Phosphocreatine levels fell to about two-thirds of their control values and remained at that level despite a gradual decline in seizure activity; (2) intracellular pH declined and then remained constant, whereas seizure discharges declined; (3) adenosine triphosphate levels remained constant at their control values. These new, lower levels of brain phosphocreatine and intracellular pH were largely unaffected by increases in seizure activity brought about by elevation of blood pressure from levels too low to support adequate cerebral perfusion, by waning of anticonvulsant drug effect, or by repeated doses of bicuculline.

Acid-Base Equilibrium↗
PubMed1984

Homonuclear 1H double-resonance difference spectroscopy of the rat brain in vivo.

We have used 1H homonuclear double-resonance difference spectroscopy at 360.13 MHz to resolve specific metabolite resonances in the brains of intact rats. Metabolite resonances resolved include previously obscured proton resonances of alanine, gamma-aminobutyric acid (GABA), glutamate, and taurine. The gamma-aminobutyric acid alpha- and gamma-CH2 proton resonances were observed in the living rat in the difference spectrum obtained upon irradiation of the beta-CH2 proton resonance at 1.91 ppm. A 3-fold increase in the intensity of the alpha- and gamma-CH2 resonances of gamma-aminobutyric acid was observed 30 min after death. The alpha-CH and gamma-CH2 resonances of glutamate were also resolved in vivo by selective irradiation of the beta-CH2 protons to which they are spin-coupled. In addition, this technique was used to observe the beta-CH3 protons of lactate through the intact scalp of a rat. Large lipid signals arising from scalp tissue were eliminated in the difference spectrum, revealing the lactate beta-CH3 resonance.

Alanine↗
PubMed1984

Detection of cerebral lactate in vivo during hypoxemia by 1H NMR at relatively low field strengths (1.9 T).

1H NMR was used to monitor lactate production and clearance during hypoxemia and recovery in the rabbit brain at the relatively low magnetic-field strength of 1.89 T. An array of conventional physiological variables were recorded simultaneously with spectrum acquisition, including the electroencephalogram and electrocardiogram. The sensitivity and spectral resolution achieved at this field strength should be applicable to studies of human brain pathophysiology in the large-bore magnets now available.

Anaerobiosis↗
PubMed1983

Natural abundance Carbon-13 nuclear magnetic resonance spectroscopy of liver and adipose tissue of the living rat.

We have employed the topical magnetic resonance (TMR) technique to obtain natural abundance 13C nuclear magnetic resonance (NMR) spectra from liver and adipose tissue in the living rat. Experiments were performed in a TMR magnet (20-cm diameter) with a two-turn radio-frequency coil ("surface" coil) combined with a focused static magnetic field. The in vivo spectra that were obtained at 20.2 MHz have been assigned by comparison with those from excised organs obtained in a conventional spectrometer operating at 90.5 MHz. Signals in the TMR spectra corresponding to carbons of the carbohydrates, glucose and glycogen, and of the lipids, triglycerides and phospholipids, have been resolved in vivo and assigned. The effects of chronic modification of dietary fat and carbohydrate on the in vivo spectra have been investigated. The levels of carbohydrates and of saturated and unsaturated fats in the liver as measured by 13C TMR reflect the relative amounts of these compounds in the long-term diet.

Adipose Tissue↗
PubMed1983

In vivo 31P-NMR studies of myocardial high energy phosphate metabolism during anoxia and recovery.

31P NMR spectra of heart in-situ in live guinea pigs were obtained continuously in 20.5 s time blocks during 3 min of anoxia, during subsequent reoxygenation and, in separate animals, during terminal anoxia. Reversible anoxia resulted in rapid degradation of phosphocreatine (t 1/2 = 54.5 +/- 2.5 s) which recovered fully during reoxygenation. Heart Pi increased during anoxia and returned to basal levels after oxygen was restored. During 3 min of anoxia, no significant changes in ATP levels or pH were detected. The results demonstrate that it is feasible to measure rapid fluxes of high energy phosphates by 31P NMR in intact animals during and after anoxic stress to the myocardium.

Animals↗
PubMed1983

In vivo phosphorus-31 nuclear magnetic resonance reveals lowered ATP during heat shock of Tetrahymena.

Cells synthesize a characteristic set of proteins--heat shock proteins--in response to a rapid temperature jump or certain other stress treatments. The technique of phosphorus-31 nuclear magnetic resonance spectroscopy was used to examine in vivo the effects of temperature jump on two species of Tetrahymena that initiate the heat shock response at different temperatures. An immediate 50 percent decrease in cellular adenosine triphosphate was observed when either species was jumped to a temperature that strongly induces synthesis of heat shock proteins. This new adenosine triphosphate concentration was maintained at the heat shock temperature.

Adenosine Triphosphate↗
PubMed1983

Structure and metabolism of mammalian liver glycogen monitored by carbon-13 nuclear magnetic resonance.

Natural-abundance 13C NMR signals from glycogen are observable in situ within the perfused livers of rats. The nuclear magnetic relaxation properties (T1, T2, eta + 1) of glycogen were measured for glycogen in situ and in vitro and were found to be identical. All of the carbon nuclei in glycogen contribute to the high-resolution NMR spectrum, in spite of glycogen's very large molecular weight. The metabolism of glycogen in situ in the perfused rat liver was followed by 13C NMR. Stimulation of the fed rat liver by physiological glucagon levels led to rapid glycogenolysis. Perfusion of the liver with [1-13C]glucose led to net glycolysis, with concomitant scrambling of the label from C1 to C6 due to triosephosphate isomerase activity.

Animals↗
PubMed1983

High-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo.

1H NMR spectra at 360.13 MHz were obtained of the rat brain in vivo by using a surface coil placed over the skull. Resonances of numerous metabolites were identified by comparison with the 1H NMR spectra of excised rat brain tissue and acid extracts of the tissue. Changes in cerebral lactate levels resulting from the administration of gas mixtures low in oxygen were monitored in the in vivo brain spectra with a time resolution of 2.3 min. The electroencephalogram and electrocardiogram were recorded simultaneously during the NMR experiment. Reversibility of the hypoxic response was documented when, upon oxygen administration, cerebral lactate returned to its prehypoxic level. These experiments demonstrate the applicability of high-resolution 1H NMR to monitor pathophysiology of brain metabolism in real time.

Animals↗
PubMed1983

39K, 23Na, and 31P NMR studies of ion transport in Saccharomyces cerevisiae.

The relationship between efflux and influx of K+, Na+, and intracellular pH (pHin) in yeast cells upon energizing by oxygenation was studied by using the noninvasive technique of 39K, 23Na, and 31P NMR spectroscopy. By introducing an anionic paramagnetic shift reagent, Dy3+(P3O5(-10))2, into the medium, NMR signals of intra- and extracellular K+ and Na+ could be resolved, enabling us to study ion transport processes by NMR. Measurements showed that 40% of the intracellular K+ and Na+ in yeast cells contributed to the NMR intensities. By applying this correction factor, the intracellular ion concentrations were determined to be 130-170 mM K+ and 2.5 mM Na+ for fresh yeast cells. With the aid of a home-built solenoidal coil probe for 39K and a double-tuned probe for 23Na and 31P, we could follow time courses of K+ and Na+ transport and of pHin with a time resolution of 1 min. It was shown that H+ extrusion is correlated with K+ uptake and not with Na+ uptake upon energizing yeast cells by oxygenation. When the cells were deenergized after the aerobic period, K+ efflux, H+ influx, and Na+ influx were calculated to be 1.6, 1.5, and 0.15 mumol/min per ml of cell water, respectively. Therefore, under the present conditions, K+ efflux is balanced by exchange for H+ with an approximate stoichiometry of 1:1.

Aerobiosis↗
PubMed1983

In vivo carbon-13 nuclear magnetic resonance studies of heart metabolism.

Guinea pig heart metabolism was studied in vivo by 13C NMR at 20.18 MHz. High-quality proton-decoupled 13C NMR spectra with excellent signal-to-noise ratios and resolution could be obtained in 6 min. Natural-abundance spectra showed resonances that could be assigned to fatty acids, but glycogen was not seen. During intravenous infusion of D-[1-13C]glucose and insulin, the time course of myocardial glycogen synthesis was followed serially for up to 4 hr. Anoxia resulted in degradation of the labeled glycogen within 6 min and appearance of 13C label in lactic acid. Infusion of sodium [2-13C]acetate resulted in incorporation of label into the C-4, C-2, and C-3 positions of glutamate and glutamine, reflecting "scrambling" of the label expected from tricarboxylic acid cycle activity. Examination of the 31P NMR spectrum of the guinea pig heart in vivo demonstrated no change in the high-energy phosphates during the time periods of the 13C NMR experiments. Our studies indicate that 13C NMR is a unique non-destructive tool for the study of heart metabolism in vivo.

Acetates↗
PubMed1983

Cerebral metabolic studies in vivo by 31P NMR.

31P NMR studies on the brains of living rabbits were carried out at 32 MHz in a spectrometer having a 200-mm clear bore. Paralyzed pump-ventilated animals under nitrous oxide analgesia were inserted into the 1.89-T field and signals were focused in the brain by using a 4-cm surface coil. Several conventional physiological variables were monitored together with 31P spectra during induction and reversal of insulin shock and hypoxic hypoxia sufficient to abolish the electroencephalogram and during status epilepticus. A reversible decrease in phosphocreatine stores accompanied by an increase in Pi was detected during hypoglycemia and hypoxia. Similar changes were observed in prolonged status epilepticus but were not reversed. ATP levels fell about 50% in hypoglycemia but only slightly in the other two metabolic stresses. Intracellular pH rose in hypoglycemia; in status epilepticus and hypoxia it fell, but only when cardiovascular function was severely impaired. From the measured NMR parameters and the assumptions (i) that creatine kinase was at equilibrium and (ii) that the creatine/phosphocreatine pool was constant, it was possible to calculate the relative changes in cytoplasmic ADP levels associated with these metabolic disturbances.

Animals↗