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S Nioka

Publications and source records attributed to S Nioka.

At least 55 records · Page 3Linked to original sources
PubMed1990

Mechanism of fatty acid effect on myocardial oxygen consumption. A phosphorus NMR study.

The calorigenic effect of fatty acids on the intact myocardium was investigated in isolated rat hearts perfused with a phosphate-free bicarbonate buffer. 31P-NMR spectra were accumulated in a Fourier transform high-field spectrometer during titration of the heart with varying concentrations of hexanoate. Oxygen consumption, coronary flow, left ventricular pressure development, heart rate and tissue surface fluorescence of nicotinamide-adenine nucleotides were monitored simultaneously. It was found that hexanoate within a range of 40 to 800 microM increased the reduction of NADH/NAD, increased oxygen consumption and increased the phosphocreatine/inorganic phosphate ratio in a concentration-dependent manner. The results suggest that the fatty acid-induced increase in oxygen consumption is not due to a primary effect on the cellular energy state resulting from a decrease in the P/O ratio or uncoupling of the mitochondria but due to an increase in the thermodynamic driving force.

Animals↗
PubMed1990

Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion.

Two metabolically distinct cell populations were detected when two peaks of inorganic phosphate (Pi), corresponding to two pHi values, were recorded by Phosphorus Magnetic Resonance Spectroscopy (31P MRS). One cell population, having intracellular pH (pHi) values less than 6.3, was thought to contain neither PCr (phosphocreatine) nor ATP and was thus considered metabolically unstable or inactive. The second cell population, having normal or near normal pHi, was considered metabolically active with adequate values of ATP and PCr. We can therefore further analyze the bioenergetics in this cell population. The results were based upon studies of 14 ischemic dogs that were anesthetized with 2% isoflurane and ventilated. The amount of Pi associated with the acidic cell population (low pHi) was used to calculate the fraction of metabolically inactive brain tissues. This value correlated well with the ATP depletion of the total cell population. This suggests that in the acidic cell population, PCr and ATP supplies were depleted by dephosphorylation during ischemia, leading to an accumulation of acidic Pi. In addition, ATP synthesis in this population may be inhibited by the low intracellular pH. On the other hand, the bioenergetic state of the metabolically stable cell population having a nearly neutral pHi changed markedly during ischemia. The PCr/Pi dropped to 0.8 and the phosphorylation potential (PP) dropped to 10 mM-1 from 40 mM-1. With reperfusion, two distinct patterns of responses were observed. One group showed the restoration of ATP (recovery group) whereas the second group did not (non-recovery group). After 3 h of reperfusion, the ATP restored group showed complete recovery of PCr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Oxygen dependence of energy state and cardiac work in the perfused rat heart.

The relationship between oxygen concentrations in arteries, cytosol, and mitochondria and high energy phosphate metabolism was studied in perfused rat hearts subjected to low and high workloads during gradual hypoxia. PCr, ATP, and Pi were measured by 31P-NMR. Myoglobin oxygenation and cytochrome aa3 oxidation were measured by the optical method. When influent oxygen tension was decreased gradually, PCr, ATP, %MbO2, %Cytaa3, cardiac work and MvO2 decreased while Pi and Pi/PCr increased in Langendorff and working hearts. These changes occurred, however, at higher PaO2 values in working hearts. The decrease of %MbO2 and %Cytaa3 in Langendorff hearts was parallel where the ratio of %MbO2 / %Cytaa3 was 1:1. However, this ratio was more than 1:1 in working hearts. It had been demonstrated that oxygen gradients change with changing oxygen consumption. Metabolic and heart work changes occurred simultaneously and significant changes occurred at low levels of %MbO2 and %Cytaa3. Some differences were observed between Langendorff and working hearts. Oxidative phosphorylation is a good indicator of ATP synthesis during hypoxia and is regulated by the intracellular oxygen concentration as well as oxygen gradients.

Animals↗
PubMed1990

Activation of the Na+, K(+)-ATPase in Narcine brasiliensis.

The in vivo activation and turnover rates of the sodium pump (Na+, K(+)-ATPase) were investigated in the electrocytes of the electric organ of the elasmobranch Narcine brasiliensis. The Narcine electric organ appears to be an excellent model for the study of sodium pump activation in an excitable tissue. The sodium transmembrane gradient and high-energy phosphagens were concurrently measured by 23Na and 31P NMR spectroscopy. The resting electric organ, which depends primarily on anaerobic metabolism, displays a high concentration of phosphocreatine (PCr). It has an intracellular sodium concentration ([Na+]i) of 20 +/- 10 milliequivalents/liter as estimated by NMR. Electrical stimulation of the nerves innervating the electric organ results in an increase in [Na+]i in the electrolyte and rapid depletion of PCr. Ouabain causes an 85% decrease in utilization of high-energy phosphagens, indicating that rapid PCr turnover in this tissue is mainly due to Na+, K(+)-ATPase activity. From these data we can determine that the rate of sodium pump turnover increases by greater than 3 orders of magnitude within several hundred milliseconds. In excised unstimulated electric organ slices, changes in [Na+]i equivalent to those occurring with stimulation, but induced by hyperosmolar conditions, do not result in increased PCr hydrolysis. We conclude that cholinergic stimulation of the electric organ causes a rapid and extremely large increase in sodium pump turnover, which is regulated predominantly by factors other than [Na+]i.

Animals↗
PubMed1990

Experimental brain ischaemia: assessment of injury by magnetic resonance spectroscopy and histology.

Phosphorus magnetic resonance spectroscopy (31P-MRS) was made to measure changes in brain high energy phosphate compounds, adenosine triphosphate (ATP) and phosphocreatine (PCr), inorganic phosphorus (Pi) and intracellular pH (pHi) during a prolonged period of incomplete brain ischaemia produced, in anaesthetized dogs, by bilateral carotid occlusion together with haemorrhagic hypotension for intervals of up to 300 min. Mean arterial blood pressure (MABP) was lowered in a stepwise fashion, until signs of metabolic decompensation (as estimated by MRS) occurred. At that point MABP was varied against further evidence of metabolic decompensation in an attempt to maintain a more constant degree of insult. At the end of the ischaemic period MABP was restored and the animals observed during a 3 h recovery period. At the end of the recovery period the brains were perfusion-fixed for histological examination. A semi-quantitative method of histological evaluation was used to determine the degree of histological damage. This permitted assignment of an 'ischaemic score' to the tissue sampled from each animal. Comparisons were then made between the magnitude of this 'ischaemic score' and the changes in metabolic and physiological variables (ATP, PCr, pHi and MABP) as well as an estimator of phosphorylation potential (PCr/Pi), which were all measured during the ischaemic insult. Histological examination showed a wide variety of neuronal alterations, including dark and pale type injury, which correlated directly with the metabolic derangements brought about by ischaemia. The degree of damage determined from this histological assessment correlated best with the duration and degree of change in PCr/Pi, supporting the use of this ratio as a critical index of cellular energy state. In particular there was a strong linear relationship between the degree of leucocyte recruitment and changes in PCr/Pi. To summarize, metabolic changes, determined by MRS, correlate with the degree of histological damage, and in turn, the classical descriptions of acute ischaemic neuronal injury appear to be validated by MRS determinations of metabolic changes during ischaemia.

Adenosine Triphosphate↗
PubMed1990

Oxidative phosphorylation system during steady-state hypoxia in the dog brain.

The relationship between biochemical and physiological responses and tissue O2 during hypoxia was investigated in vivo in the dog brain by 31P nuclear magnetic resonance (NMR) spectroscopy. Our findings demonstrate how ATP synthesis in the brain can be maintained during hypoxia because of compensatory changes in NADH, ADP, and Pi. Eleven beagle dogs were anesthetized and mechanically ventilated, and a steady-state graded hypoxia was induced by decreasing the fraction of inspired O2 (FIO2) stepwise at 20-min intervals. Biochemical metabolites were measured using 31P-NMR and fluorescence spectroscopy. When sagittal sinus O2 partial pressure (PVO2) had decreased to 15 Torr, NADH increased by 30%, Pi increased by 50%, and phosphocreatine (PCr) decreased by 20%. In contrast, ATP remained constant. There was a 10% increase in ADP in dogs that maintained a steady temperature, but ADP decreased by as much as 30% in dogs in which body temperature decreased with the falling PVO2. PCr/Pi was logarithmically related to the phosphorylation potential during steady-state hypoxia. Compensation for the O2 lack is attributed to increases in ADP, Pi, and NADH as a result of the reciprocal relationship of the Michaelis-Menten equation. If the Michaelis-Menten constants (Km) of ADP, Pi, and O2 are the same as determined in vitro in mitochondria, the minimum brain cytosolic O2 capable of maintaining a steady-state ATP is near its Km (0.1 Torr) at a PVO2 of 7.5 Torr. At this critical O2 level, PCr/Pi is 0.9, intracellular pH is 6.75, phosphorylation potential is 38.5 mM-1, and the calculated maximum velocity of ATP formation by oxidative phosphorylation is 55% of normal.

Adenosine Diphosphate↗
PubMed1990

Cerebral energy metabolism and oxygen state during hypoxia in neonate and adult dogs.

The relationship between a noninvasive determination of relative oxygen saturation of Hb circulating in brain tissue (StO2) and energy metabolism was investigated with respect to age [dogs in three age groups (0 to 6-d-old, 7- to 21-d-old, and adults)] and to severity of brain hypoxia using double beam spectroscopy of Hb deoxygenation and nuclear magnetic resonance spectroscopy of energy metabolism. The in vivo oxy-Hb dissociation was determined from the relationship between StO2 curve in the adult dog brain and sagittal sinus oxygen partial pressure during graded hypoxemia and found to be sigmoidal with an oxygen dissociation constant of 26.6 mm Hg. This agreed with an in vitro determination for oxygen dissociation constant of 28.2 mm Hg in adult dog red cells. The arterial oxygen pressure at which brain StO2 was reduced by 50% was shifted toward the right with increasing age (22.2, 33.8, and 40.8 mm Hg, respectively). This correlated with an in vitro oxygen dissociation constant of red cell Hb of 17.0, 22.3, and 28.2 mm Hg in the three age groups, respectively. The phosphocreatine-inorganic phosphate ratio (PCr/Pi) was used to relate changes in cellular energy metabolism during hypoxia with changes in StO2. There was no change in PCr/Pi when StO2 had decreased to 50% of the control value. However, when the brain StO2 had decreased to between 7 and 15%, a reduction of PCr/Pi to 50% of the normoxic value occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

Time-resolved spectroscopy of hemoglobin and myoglobin in resting and ischemic muscle.

Difficulties of quantitation of hemoglobin/myoglobin absorption changes in muscle have led to the development of a new approach using short pulses of light. This method uses input light pulses sufficiently short so that the time course of travel of light through the brain can be precisely measured. The time of arrival of light at the detector gives the optical path length, given the velocity of light in tissues. The intensity profile of photon migration in tissues permits determination of the path length that the exiting photons have traveled and the concentration change of the pigments. A cavity-dumped liquid dye laser illuminates the tissue with 130-ps pulses detected as 600-ps duration at a half height at 3.0-cm distance from the input point. The decay of intensity from the 50% point onward to 0.1% follows a logarithmic function of slope mu which is attributed to the total absorption coefficient of the tissue. Increments of mu due to deoxyhemoglobin absorption at 760 and 630 nm are used to calculate the concentration change. This permits the calculation of the path length for continuous light measurements of 2 cm for a particular geometry. Variation of the wavelength of the laser affords determination of a spectrum of changes in the tissue.

Adult↗
PubMed1988

The simultaneous measurements of tissue oxygen concentration and energy state by near-infrared and nuclear magnetic resonance spectroscopy.

The oxygenation and energy states of brain tissues were measured simultaneously by near-infrared photometry and nuclear magnetic resonance spectroscopy in situ. In both cat and dog, the critical hemoglobin oxygenation was 10%, below which the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) started to fall. The fall of PCr/Pi paralleled the reduction of copper in cytochrome aa3. The separation of the cytochrome aa3 signal from that of hemoglobin by our optical method was confirmed by the substitution of blood by fluorocarbon solution. The energy-oxygen diagram (PCr/Pi against hemoglobin oxygenation, HbO2) was the same in normal- and fluorocarbon substituted cats, but energy curve shifted to the right in the latter when PCr/Pi plotted against the inspired oxygen, FiO2.

Animals↗
PubMed1988

Fiber optic surface fluorometry/reflectometry and 31-p-NMR for monitoring the intracellular energy state in vivo.

Various members of the respiratory chain exhibit different optical properties in the reduced and oxidized forms, thus enabling the non-invasive monitoring of various organs in vitro as well as in vivo. Since the pioneering work of Chance, Cohen, Jobsis and Schoener in 1962, many groups of investigators adopted their approach in monitoring NADH oxidation reduction states in vivo for the brain as well as for other body organs. In 1972, we introduced flexible, optical fibers into the surface fluorometry replacing the usual "rigid" optical system used by other groups. During the last decade, this technique has been developed, improved and applied to many experimental setups in brain research and very recently was combined with 31P NMR spectroscopy for the puppy and the adult dog brain in vivo. In our system, the effects of movement artifacts and changes in blood oxygenation are negligible while the effects of tissue absorption or blood volume changes are considerable and could be minimized by subtraction of the reflectance signal from that of the fluorescence (1:1 ratio) providing the corrected fluorescence signal.

Anaerobiosis↗
PubMed1988

Brain oxidative metabolism of the newborn dog: correlation between 31P NMR spectroscopy and pyridine nucleotide redox state.

The effects of both anoxia and short- and long-term hypoxia on brain oxidative metabolism were studied in newborn dogs. Oxidative metabolism was evaluated by two independent measures: in vivo continuous monitoring of mitochondrial NADH redox state and energy stores as calculated from the phosphocreatine (PCr)/Pi levels measured by 31P nuclear magnetic resonance (NMR) spectroscopy. The hemodynamic response to low oxygen supply was further evaluated by measuring the changes in the reflected light intensity at 366 nm (the excitation wavelength for NADH). The animal underwent surgery and was prepared for monitoring of the two signals (NADH and PCr/Pi). It was then placed inside a Phosphoenergetics 260-80 NMR spectrometer magnet with a 31-cm bore. Each animal (1-21 days old) was exposed to short-term anoxia or hypoxia as well as to long-term hypoxia (1-2 h). The results can be summarized as follow: (a) In the normoxic brain, the ratio between PCr and Pi was greater than 1 (1.2-1.4), while under hypoxia or asphyxia a significant decrease that was correlated to the FiO2 levels was recorded. (b) A clear correlation was found between the decrease in PCr/Pi values and the increased NADH redox state developed under decreased O2 supply to the brain. (c) Exposing the animal to moderately long-term hypoxia led to a stabilized low-energy state of the brain with a good recovery after rebreathing normal air. (d) Under long-term and severe hypoxia, the microcirculatory autoregulatory mechanism was damaged and massive vasoconstriction was optically recorded simultaneously with a significant decrease in PCr/Pi values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of time-resolved and -unresolved measurements of deoxyhemoglobin in brain.

Continuous (CW) and pulsed light were used for the noninvasive measurement of hemoglobin oxygenation in tissues. A dual wavelength method of continuous illumination spectroscopy used 760 nm (deoxyhemoglobin peak) and 800 nm (an oxyhemoglobin-deoxyhemoglobin isosbestic point) to measure the kinetics and extent of oxyhemoglobin deoxygenation in brains during mild ischemia/hypoxia. Absorption and scattering were modeled in an artificial milk/yeast blood system, which gave an exponential relationship between absorption and optical path length to a depth of 7 cm. Time-resolved spectroscopy (10-ps resolution) afforded a display of the times and distances of arrival of photons emitted by the cat brain in response to a 10-ps input pulse. The emitted photons rose to a peak in a fraction of a nanosecond and declined exponentially over a few nanoseconds. The half-time of exponential decay corresponds to photon migration over a distance of 4 cm. Exponential light emission continued for several more nanoseconds when the brain was encased by the skull, which plays a key role in prolonging light emission. The exponential decline of light intensity has a value [exp(-microL)], where L is the path length determined from the time/distance scale and mu is the characteristic of the migration of light in the brain. The factor mu is increased by increasing absorption, and mu' = epsilon C where epsilon and C are the Beer-Lambert parameters of extinction coefficient (epsilon) and concentration (C). Thus, deoxyhemoglobin can be quantified in brain tissues.

Animals↗
PubMed1988

Total CA activity in isolated perfused guinea pig lung by 18O-exchange method.

The rate of exchange of 18O between alveolar CO2 and lung water was measured in isolated perfused guinea pig lungs to quantify carbonic anhydrase (CA) activity. The average lung CA activity, with a reaction velocity constant of 5.32 +/- 2.2 s-1, is sufficient to accelerate CO2 reactions in lung water by two orders of magnitude over the uncatalyzed rate at 22 degrees C and a PCO2 of 40 Torr. Three sulfonamide inhibitors of CA with different human erythrocyte membrane permeabilities were used to determine the availability of the enzyme to the perfusate. Ethoxzolamide, the most permeable at 0.1 microM (100 times its inhibition constant, of Ki) inhibited 85% of enzyme activity after exposure of the lung for 3 min and 94% of enzyme activity after 30 min, whereas 1.25 microM (320 times its Ki) acetazolamide (1/165 as permeable) only inhibited CA 28% at 3 min and 75% at 30 min. Benzolamide (less than 1/1,000 as permeable) at 4 microM (1,000 times its Ki) inhibited only approximately 17% of control CA activity by 5 min and 48% by 30 min after the start of perfusion. These data indicate the CA available to pulmonary capillary plasma is approximately 10% of the total lung CA activity, in agreement with published measurements on the homogenized lung.

Animals↗
PubMed1987

Cerebral energy metabolism measured in vivo by 31P-NMR in middle cerebral artery occlusion in the cat--relation to severity of stroke.

The energy metabolism of the brain has been measured in a middle cerebral artery (MCA) occlusion model in the cat utilizing 31P-nuclear magnetic resonance (NMR). 31P-NMR spectra were serially obtained during 2 h of ischemia and a subsequent 4-h recovery period. The ratio of creatine phosphate (PCr) to inorganic phosphate (Pi) (PCr/Pi) showed a precipitous decrease in parallel with changes in electroencephalographic (EEG) amplitude in severe strokes during ischemia as well as during recirculation. Animals with mild strokes, as determined by EEG criteria, exhibited a much smaller decrease in PCr/Pi during ischemia. In the severe strokes, there was a splitting and significant shift of the Pi peak immediately after occlusion. In addition, the shifted Pi peak rapidly increased and remained elevated throughout the study. In the mild strokes, Pi also increased, but not as markedly. Intracellular pH determination by chemical shift of the Pi peak revealed a decrease from 7.1 to 6.2-6.3 during ischemia and the subsequent recovery period in the animals with severe strokes, whereas the pH in the animals with mild strokes did not show a significant change. A gradual decrease in adenosine triphosphate (ATP) to 57-79% of the control was exhibited in severely stroked animals during both the ischemia and the recovery period, whereas there was no change in ATP in the mild stroked animals. These results suggest that the dynamic process of pathophysiological changes in an MCA occlusion model in the cat leads to significant differences in cerebral metabolism between animals with mild and severe strokes.

Adenosine Triphosphate↗