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R S Balaban

Publications and source records attributed to R S Balaban.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of substrate on mitochondrial NADH, cytosolic redox state, and phosphorylated compounds in isolated hearts.

The effect of metabolic substrates on the relation among cytosolic redox state (NADHc/NAD+) mitochondrial NADH (NADHm), and [ATP]/([ADP] x [Pi]) was studied in isolated working rabbit hearts. Substrates were varied from 5.6 mM glucose alone to glucose in combination with 10 mM lactate and/or 10 mM pyruvate while afterload and preload were held constant. Changes in NADHm were determined from epicardial NADH fluorescence. The ratio of glycerol 3-phosphate (G-3-P) to dihydroxyacetone phosphate (DHAP), determined from tissue extracts, was used as an index of cytosolic redox. Myocardial 31P metabolites were measured using nuclear magnetic resonance spectroscopy. The addition of pyruvate to the perfusion medium caused increases in myocardial oxygen consumption (MVo2), NADHm fluorescence, phosphocreatine (PCr), and [ATP]/([ADP] x [Pi]) and a decrease in NADHc/NADc+ (decreased G-3-P/DHAP). Although the addition of lactate to the perfusion medium caused an increase in NADHm similar to pyruvate, MVo2 and PCr did not change significantly, [ATP]/([ADP] x [Pi]) increased less than with pyruvate, and there was an increase in NADHc/NADc+. The findings suggest that variations in the cytosolic redox state do not necessarily result in obligatory changes in either the mitochondrial redox state or in the [ATP]/([ADP] x [Pi]). This implies that under the conditions of this study an equilibrium is not maintained between [ATP]/([ADP] x [Pi]) and NADHc/NADc+. Furthermore, similar levels of NADHm can be associated with different values for [ATP]/([ADP] x [Pi]) and MVo2, depending on the substrates available to the heart.

Adenosine Diphosphate↗
PubMed1995

A multimode dynamometer for in vivo MRS studies of human skeletal muscle.

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.

Adult↗
PubMed1995

Magnetic resonance imaging of the galactosemic dog eye using magnetization transfer contrast.

Magnetization transfer contrast (MTC) enhanced magnetic resonance (MR) imaging is a technique that generates high contrast images based on characteristic tissue differences resulting from the interaction of water and macromolecules. In this study, the feasibility of applying this technique to documenting the progression of osmotic sugar cataract formation was investigated in male beagles, initially 6 or 24 month old, fed a diet containing 30% galactose. MTC enhanced magnetic resonance imaging was periodically conducted on these animal's eyes at 2-Tesla. The lens MR images were compared to photographs obtained by photo-slit lamp and retroillumination photography. The MTC technique provided improved image details of the lens and anterior segment that documented osmotic changes from initial cortical vacuole formation to cortical and nuclear changes associated with advanced sugar cataracts. The latter could not be observed by photo-slit lamp or retroillumination photography.

Animals↗
PubMed1994

The design and test of a new volume coil for high field imaging.

A major problem in the development of high field (> 100 MHz) large volume (> 6000 cm3) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B1 homogeneity.

Equipment Design↗
PubMed1994

Comparison of EPI gradient-echo contrast changes in cat brain caused by respiratory challenges with direct simultaneous evaluation of cerebral oxygenation via a cranial window.

A gradient-echo echo planar imaging (EPI) sequence has been used to generate images of cat brain during respiratory challenges. Direct spectrophotometric measurements have been made simultaneously in order to correlate the changes in oxygen saturation as measured by spectrophotometry with the image intensity changes seen in the gradient-echo images. When blood volume remains approximately constant, as derived from the spectrophotometry data, good correlation is seen between calculated plots made of changes in the transverse relaxation rate, delta R2*, and the oxygen saturation as measured by spectrophotometry for much of the time course of the respiratory challenges of anoxia, apnea and hypercapnia. In some cases, the correlation is poorer during the recovery periods of the apnea and anoxia challenges. Those lower correlations can often be accounted for by changes in blood volume, which also affects the NMR relaxation rate. These results contribute to the understanding of the image intensity changes seen during functional brain imaging studies in humans.

Animals↗
PubMed1994

Effect of cardiac flow on gradient recalled echo images of the canine heart.

The effect of coronary flow on the signal intensity of gradient recalled echo (GRE) MR images of the canine heart was evaluated at 4 T. Using a fully instrumented canine model, hyperfusion (local adenosine infusion) and ischemia (local occlusion) were evaluated while coronary blood flow and venous oxygen tension were monitored. These studies demonstrated an increase in GRE signal intensity with increases in coronary blood flow and venous oxygenation. A local occlusion resulted in a small decrease in signal intensity in the affected area of the heart. The dependence of the signal changes on TE and TR indicated that the effects of high flow were associated with changes in the apparent T2 and T1. Both relaxation effects could reflect changes in tissue blood volume associated with the conditions studied. In addition, the apparent T2 changes were consistent with alterations in total tissue deoxyhemoglobin concentration and the changes in apparent T1 were consistent with inflow effects.

Adenosine↗
PubMed1994

Mitochondrial F1-ATPase activity of canine myocardium: effects of hypoxia and stimulation.

Recent studies have suggested that modifications in mitochondrial F1-adenosinetriphosphatase (ATPase) activity may play an important role in the regulation of myocardial oxidative phosphorylation. The goal of the present study was to develop and characterize an assay of F1-ATPase activity that could be performed repeatedly on an intact heart under various physiological states. With the use of submitochondrial particles prepared from biopsy samples of canine myocardium, we found reproducible F1-ATPase activity when normalized to the activity of the intramitochondrial enzyme citrate synthase. The oligomycin-sensitive component of the ATPase activity was found to be mainly F1-ATPase. F1-ATPase activity of normal myocardium increased by incubation in high salt-pH buffer, suggesting baseline inhibition. Five minutes after global ischemia, F1-ATPase activity decreased to 60% of baseline. Hypoxia for 10 min resulted in no significant change in F1-ATPase activity. With phenylephrine infusion, myocardial oxygen consumption more than doubled, whereas F1-ATPase activity increased by approximately 30%. Both returned to baseline levels after discontinuation of the drug. With the use of an assay developed to measure F1-ATPase activity of intact myocardium, changes of the enzyme activity were found during both ischemia and at increased work loads. These data suggest that alterations of F1-ATPase activity may contribute to the regulation of myocardial oxidative phosphorylation.

Adenosine Triphosphatases↗
PubMed1994

Nonglucose substrates increase glycogen synthesis in vivo in dog heart.

The effects of circulating nonglucose substrates on insulin-stimulated cardiac glycogen synthesis were studied in the dog heart in vivo using 13C-nuclear magnetic resonance (-NMR) and arteriovenous difference techniques. [1-13C]glycogen was monitored in hearts during an intravenous infusion of 20 mU/min insulin and glucose while [1-13C]glucose (10 mg/min) was infused into the left anterior descending coronary artery. When 1 mmol/min of lactate, pyruvate, or beta-hydroxybutyrate was added to the venous infusion, the measured rate of glycogen synthesis was increased, on average, sixfold. It was not increased further after a subsequent 10-min infusion of 5 micrograms/min epinephrine. Lactate extraction increased from 0.18 +/- 0.05 to 0.62 +/- 0.11 mumol.min-1.g wet wt-1 during lactate infusion, whereas glucose extraction did not change significantly (0.15 +/- 0.05 mumol.min-1.g wet wt-1 at 45 min of insulin and glucose infusion to 0.09 +/- 0.02 mumol.min-1.g wet wt-1 at 45 min of the lactate infusion). Therefore, the uptake and oxidation of circulating nonglucose substrates redirects the fate of extracted glucose from glycolysis to glycogen synthesis in the dog heart in vivo.

3-Hydroxybutyric Acid↗
PubMed1993

Analysis of water-macromolecule proton magnetization transfer in articular cartilage.

These studies were designed to establish which structural elements of cartilage are responsible for proton magnetization transfer between water (Hf) and macromolecules (Hr) observed in MRI studies on articular cartilage. Saturation transfer techniques were used to monitor magnetization transfer in vitro on samples of the two major constituents of cartilage: collagen and proteoglycan. Articular cartilage samples were also evaluated in vitro before and after the removal of the proteoglycan fraction. Isolated hydrated collagen exhibited a significant proton magnetization transfer rate with water. In contrast, proteoglycans exhibited no proton magnetization transfer. Articular cartilage, in vitro, exhibited a high degree of magnetization transfer with water protons consistent with previous MRI studies in vivo. Enzymatic removal of proteoglycan from the cartilage did not alter the magnetization transfer rate between Hr and Hf. These data demonstrate that the structure and concentration of the collagen matrix are the predominant determinants of the magnetization transfer process in articular cartilage with little or no contribution from proteoglycans. This specificity of the magnetization transfer effect may prove useful in the noninvasive evaluation of cartilage composition and structure in vivo.

Animals↗
PubMed1993

Functional mapping of the human visual cortex at 4 and 1.5 tesla using deoxygenation contrast EPI.

The effects of photic stimulation on the visual cortex of human brain were studied by means of gradient-echo echo-planar imaging (EPI). Whole-body 4 and 1.5 T MRI systems, equipped with a small z axis head gradient coil, were used. Variations of image intensity of up to 28% at 4 T, and up to 7% at 1.5 T, were observed in primary visual cortex, corresponding to an increase of blood oxygenation in regions of increased neural activity. The larger effects at 4 T are due to the increased importance of the susceptibility difference between deoxygenated and oxygenated blood at high fields.

Adult↗
PubMed1993

Magnetization transfer characterization of hypertensive cardiomyopathy: significance of tissue water content.

Magnetization transfer measurements offer the potential for specific noninvasive tissue characterization. The goal of the present study was to determine if changes in magnetization transfer would accompany the myocardial remodeling that occurs with hypertrophic cardiomyopathy. Using 40-week spontaneously hypertensive rat (SHR) myocardium, T1, T2, and T1 in the presence of off-resonance irradiation (T1sat) were found to be greater compared to Wistar-Kyoto (WKY) controls. The pseudo-first order rate constant of magnetization transfer (kfor) was less in 40-week SHR compared with WKY while the ratio of equilibrium magnetization in the presence and absence of off-resonance irradiation (MsIM0) was not different. The extent to which observed interspecies differences in tissue water content affected these parameters was investigated by dehydrating normal and hypertrophic myocardium. Significant correlations found between tissue water content and T1, T2, T1sat and kfor, but not MsIM0, suggested changes in tissue water dominated the observed interspecies differences in relaxation parameters. Thus, ventricular remodeling in hypertrophic cardiomyopathy does not alter magnetization transfer though the accompanying change in tissue water content influences water proton relaxation.

Age Factors↗
PubMed1993

Effects of afterload and heart rate on NAD(P)H redox state in the isolated rabbit heart.

NAD(P)H redox state was monitored using surface fluorescence in isolated, normothermic, working rabbit hearts under conditions of limited substrate (glucose alone) and abundant substrate (glucose + lactate). To alter work, afterload was varied between 75 and 150 cmH2O or heart rate was increased in steps until no further increase in myocardial oxygen consumption (MVO2) occurred. Alterations in afterload did not cause a significant change in NAD(P)H fluorescence. Progressive increases in heart rate did not alter NAD(P)H emission until MVO2 began to decline (approximately 300 beats/min), ventricular performance decompensated, and there was evidence of ischemia, at which time NAD(P)H fluorescence increased. Although the addition of 3 mM lactate to the perfusate resulted in a rapid increase in NAD(P)H fluorescence, NAD(P)H fluorescence still did not respond to altered workload. The results suggest that NAD(P)H redox state is not the primary stimulus for increased myocardial respiration secondary to tachycardia or afterload. However, despite increased rates of cardiac work, NAD(P)H was maintained at a relatively stable level, suggesting that reducing equivalent supply to the electron transport chain increases in parallel with increased MVO2.

Animals↗
PubMed1993

Pyruvate and lactate metabolism in the in vivo dog heart.

Pyruvate increases the phosphorylation potential in perfused heart to a greater extent than the closely correlated substrate L-lactate. Therefore, metabolism of these compounds was studied in the myocardium of intact dogs. Phosphocreatine/ATP was increased 23% at 5.3 mM plasma pyruvate but was not significantly increased by lactate except at the highest concentration (17.5 mM in blood). Calculated [ADP] fell during pyruvate infusion from 51.5 +/- 2.0 to 38.6 +/- 3.3 microM but did not change significantly during lactate infusion. Intracellular free [Mg2+] fell from 705 +/- 53 to 498 +/- 30 microM at the highest pyruvate infusion and from 692 +/- 112 to 417 +/- 19 microM with lactate infusion. Extraction of both substrates was linear at low concentrations, reaching 0.56 mumol lactate.min-1.g wet wt-1 at 17.5 mM blood lactate and 0.58 mumol pyruvate.min-1.g wet wt-1 at 5.3 mM plasma pyruvate. Therefore, lactate uptake was almost five times lower than pyruvate uptake at similar concentrations. Elevated pyruvate (> 3 mM) resulted in almost complete inhibition of net lactate uptake. Infused [3-13C]lactate or -pyruvate gave rise to labeled glutamate and alanine in vivo, but labeled lactate was not visible when [3-13C]pyruvate was the substrate. The 13C enrichment of myocardial lactate was similar to alanine and acetyl CoA with infused [3-13C]lactate but was only one-half that of alanine and acetyl CoA when [3-13C]-pyruvate was the substrate, indicating a possible inhibition of lactate dehydrogenase.

Animals↗
PubMed1992

Synthesis of 5-methylaminomethyl-2-selenouridine in tRNAs: 31P NMR studies show the labile selenium donor synthesized by the selD gene product contains selenium bonded to phosphorus.

An enzyme preparation from Salmonella typhimurium catalyzes the conversion of 5-methylaminomethyl-2-thiouridine in tRNAs to 5-methylaminomethyl-2-selenouridine when supplemented with selenide and ATP. Similar preparations from a Salmonella mutant strain carrying a defective selD gene fail to catalyze this selenium substitution reaction. However, supplementation of the deficient enzyme preparation with the purified selD gene product (SELD protein) restored synthesis of seleno-tRNAs. In the absence of the complementary enzyme(s), the SELD protein catalyzes the synthesis of a labile selenium donor compound from selenide and ATP. 31P NMR studies show that among the products of this reaction are AMP and a compound containing selenium bonded to phosphorus. The reaction is completely dependent on the addition of both selenide and magnesium. The dependence of reaction velocity on ATP concentration shows sigmoidal kinetics, whereas dependence on selenide concentration obeys Michaelis-Menten kinetics indicating a Km value of 46 microM for selenide.

Adenosine Monophosphate↗
PubMed1992

Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest.

Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15 degrees C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06; p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and an increase [corrected] in the intracellular acidosis normally associated with ischemia.

Acidosis, Lactic↗
PubMed1992

Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.

Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.

Adenosine Triphosphate↗