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R S Balaban

Publications and source records attributed to R S Balaban.

At least 127 records · Page 7Linked to original sources
PubMed1989

MRS of the kidney.

Many of the first magnetic resonance spectroscopy (MRS) studies ever conducted on intact biologic tissues were on the mammalian kidney. These early studies and subsequent investigations have concentrated on the evaluation of the viability and metabolic function of the kidney in vitro and in vivo. This brief overview will discuss the type of information that has been obtained on the kidney, using model systems as well as man. In these studies, MRS has provided new physiologic and biochemical data on the kidney. These include the determination of the heterogeneity of intracellular pH and the discovery of organic solutes that protect the kidney from the hostile extracellular environment it manufactures. Clinical studies have been precipitated by favorable model studies, but are still in early stages of development.

Adenosine Triphosphate↗
PubMed1989

Relation between phosphate metabolites and oxygen consumption of heart in vivo.

The relation between induced increases in cardiac work and phosphate metabolites was investigated in the canine heart in vivo to evaluate the role of ATP hydrolysis products, ADP and inorganic phosphate (Pi), in the control of myocardial oxygen consumption (MVO2). In these studies, myocardial blood flow and oxygen consumption were simultaneously measured with the 31P-nuclear magnetic resonance (NMR)-detected phosphate metabolites. Three protocols were used to increase myocardial work: pacing, epinephrine, and phenylephrine infusions. When these protocols were used, no or only slight changes in myocardial ATP, Pi, and creatine phosphate were observed with a greater than threefold increase in MVO2. The calculated intracellular free Mg concentration, ADP, and pH were also only slightly affected by these increases in work. These data indicate that a simple model involving the feedback of cytosolic ADP and Pi to the mitochondria regulating respiration is inadequate to explain respiratory control in vivo. These data suggest that some other parameters or cooperativity effects involving the phosphate metabolites must play a role in the feedback between respiration and work in the heart in vivo.

Animals↗
PubMed1989

A simple HPLC method for quantitating major organic solutes of renal medulla.

A simple high performance liquid chromatography (HPLC) method of separating and quantitating the predominant organic solutes of the renal medulla is described. These organic solutes include myo-inositol, glycerophosphorylcholine, sorbitol, betaine, and urea. Other physiologically significant solutes, including glucose and mannitol, can be separated and quantitated concurrently with this method. With the use of this technique, the organic solutes of the rabbit kidney were determined. No new organic compounds were detected by HPLC that could significantly contribute to intracellular osmolality of the medulla. The values for the organic solutes already described were similar to those obtained by more complicated and limited approaches such as classical enzymatic techniques, ion electrodes, nuclear magnetic resonance spectroscopy, and gas chromatography-mass spectroscopy.

Animals↗
PubMed1989

Acute regulation of the predominant organic solutes of the rabbit renal inner medulla.

High concentrations of organic solutes are present in the medulla of the antidiuretic kidney. However, their role in and response to acute changes in the diuretic state are unknown. In this study the organic solute content of the renal medulla was determined from extracts with the use of high-performance liquid chromatography following the acute dilution of the medullary interstitium during various forms of diuresis. After acute infusion of saline and furosemide, inner medullary urea, sodium, inositol, sorbitol, and betaine decrease significantly with no change in glycerophosphorylcholine (GPC) content. After diuresis, inner medullary urea and sodium contents eventually returned to control levels, although inositol, sorbitol, and betaine contents still remained low. Addition of antidiuretic hormone to the saline/furosemide infusion gave similar results. In contrast, induction of diuresis from mannitol infusion caused an acute decrease in all 4 organic solutes, whereas glucose infusion caused an acute decrease in all organic solutes except sorbitol. These data demonstrate that a decrease in all four organic solutes can accompany medullary dilution. However, GPC and sorbitol do not decrease when diuresis is induced by furosemide or glucose, respectively. In addition, the recovery of these compounds in a normally functioning kidney after diuresis is much slower than the regeneration of the sodium chloride and urea gradients.

Animals↗
PubMed1989

Developmental changes in the relation between phosphate metabolites and oxygen consumption in the sheep heart in vivo.

This study examines the role of phosphate metabolites in the regulation of mitochondrial oxygen consumption of the heart in vivo as a function of development. We used an open chest lamb/sheep preparation in which myocardial oxygen consumption (MVO2) was monitored via an extracorporeal shunt from the coronary sinus. Phosphate metabolites were monitored simultaneously using 31P nuclear magnetic resonance with a surface coil overlying the left ventricle. Graded infusions of epinephrine were used to increase MVO2 in both neonatal lambs (age 5-12 d, n = 8), and mature sheep (26-86 d, n = 6). The maximal increase in MVO2 achieved was 220 +/- 38% in the newborns and 350 +/- 66% in the mature animals. Associated with these increases in MVO2 in the newborn lambs are significant (P less than 0.001) decreases in PCr/ATP, and increases in calculated ADP and intracellular Pi. This was in contrast to the mature sheep, in which there were no significant changes in PCr/ATP, ADP, or Pi. In conclusion, we find that (a) there are changes in PCr/ATP, Pi, and ADP in newborn animals with moderate increases in work that are not apparent in mature animals of the same species and (b) that these changes suggest that cytosolic ATP hydrolysis products may be more important in regulation of myocardial energy metabolism in the newborn than in the adult.

Adenosine Triphosphate↗
PubMed1988

Saturation and inversion transfer studies of creatine kinase kinetics in rabbit skeletal muscle in vivo.

The steady-state kinetics of the creatine kinase reaction in rabbit skeletal muscle in vivo was investigated using inversion and saturation magnetization transfer techniques. Both techniques determined the forward rate of this reaction (creatine phosphate ATP) as approximately 0.3 s-1. This corresponds to a flux of 10 mumol creatine phosphate/s/g muscle. The saturation transfer technique underestimated the reverse reaction by approximately 56%. This result is likely due to the participation of ATP in other interactions in skeletal muscle not involving creatine phosphate.

Animals↗
PubMed1988

Deuterium NMR cerebral imaging in situ.

Nuclear magnetic resonance imaging of deuterium is demonstrated in cat brain in vivo and in situ at 4.7 T magnetic field strength. Images were acquired at 4-5% deuterium enrichment, using D2O as a nuclear spin label, with as little as 10-s time resolution. This suggests the potential application of D2O as an exogenous MRI label for quantitative flow imaging or contrast enhancement. The efficient quadrupolar relaxation mechanism of the deuterium nuclide results in a short ca. 250 ms spin-lattice relaxation time (T1). This allows for rapid signal averaging, thus increasing signal-to-noise in the deuterium image. Additionally, three widely dispersed deuterium spin-spin relaxation times (T2) are observed of ca. 10, 40, and 400 ms which provide high compartmental image contrast, thus yielding information of physiological as well as anatomical interest. T2-weighted deuterium cerebral images are presented showing marked tissue relaxation discrimination.

Animals↗
PubMed1988

Human arterial surface fluorescence: atherosclerotic plaque identification and effects of laser atheroma ablation.

In vivo plaque recognition may be important for safe and precise intra-arterial atheroma ablation during laser coronary angioplasty. This study examined the feasibility and sensitivity of utilizing quantitative fluorescence spectroscopy and video-enhanced fluorescence imaging for plaque identification in atherosclerotic human necropsy arterial wall before and after laser atheroma ablation. With wide-band (450 to 490 nm) blue light excitation, the 540 nm fluorescence intensity ratio of normal to diseased sites (n = 13) was 2.09 +/- 0.82 (p less than 0.001) and video fluorescence imaging provided enhanced delineation of atheroma surface characteristics. Continuous argon and pulsed excimer (308 nm) laser ablation of atheroma decreased fluorescence intensity ratios by 42 and 20% (p less than 0.001), respectively (that is, from abnormal to nearly normal). Low power 325 nm laser-excited fluorescence spectroscopy from normal (n = 115) and abnormal (n = 146) necropsy sites revealed an average 45% decrease in atheroma fluorescence intensity (p less than 0.0001) and changes in fluorescence spectra appearance that corresponded to plaque morphologic subtypes. Studies using a dual laser system combining 325 nm laser-excited fluorescence plaque recognition and a 480 nm pulsed dye laser for tissue ablation with common optical fibers demonstrated normalization of both fluorescence intensity and spectra appearance after laser atheroma ablation. Thus, in vitro analysis of surface arterial fluorescence by quantitative spectroscopy and video fluorescence imaging reliably differentiate plaque from normal tissue and may provide the feedback signal needed to activate a laser source for selective plaque removal.

Adult↗
PubMed1988

Survey of osmolytes in renal cell lines.

In renal medullas during antidiuresis, the extracellular fluid is hyperosmotic because of high concentrations of NaCl and urea. Under those conditions, the cells contain high concentrations of organic osmolytes, namely sorbitol, myo-inositol, glycerophosphorylcholine (GPC), and betaine to balance the extracellular hyperosmolality. These organic osmolytes increase cell osmolality without perturbing the intracellular milieu in ways that would degrade the function of cellular macromolecules. The present study surveyed a number of cell lines for the ability to survive in media with high concentrations of NaCl and/or urea and for the accumulation of organic osmolytes. Of the renal cell lines tested, MDCK, GRB-MAL1, and A6 cells proliferated in hyperosmotic media, but medullary interstitial cells LLC-PK1 and LLC-PK3 did not proliferate, nor did nonrenal HTC-BH cells, MDCK, LLC-PK1, and LLC-PK3 cells contained higher concentrations of myo-inositol, GPC, and betaine when cultured in media containing high NaCl (with or without high urea) and much lower or undetectable levels of these osmolytes when grown in isosmotic media. Sorbitol, and to a lesser extent myo-inositol, were elevated in GRB-MAL1 cells in media hyperosmotic with NaCl but not in isosmotic media. There was less accumulation of organic osmolytes when only urea was added to increase osmolality. Thus the same osmolytes were accumulated by one or another cell line in vitro as were previously found in renal medullas. These cell lines provide models for studying osmolyte accumulation.

Animals↗
PubMed1988

Activation of dehydrogenase activity and cardiac respiration: a 31P-NMR study.

31P-NMR studies were performed to determine the tissue phosphate and oxygen consumption effects of known maneuvers on the activation of pyruvate dehydrogenase during work jumps in the perfused rat heart. In control studies of the glucose-perfused heart, work jumps, with pacing, resulted in a 32% increase in oxygen consumption (QO2) from 1.72 +/- 0.09 to 2.29 +/- 0.12 mmol O2.h-1.g dry wt-1. During this transition no significant change in the high energy phosphates were detected. In contrast, work jumps did cause changes in the phosphates when the activation of pyruvate dehydrogenase was blocked with 2.5 micrograms of ruthenium red per milliliter or maximally stimulated with 11 mM pyruvate before the increase in work. The observed increase in QO2 and inorganic phosphate and calculated increase in ADP are consistent with these phosphates controlling mitochondrial respiration under these conditions. These results suggest that the activation of pyruvate dehydrogenase and/or other dehydrogenases may be an important step in the orchestration of work and QO2.

Animals↗
PubMed1988

Intracellular pH and inorganic phosphate content of heart in vivo: a 31P-NMR study.

Studies were performed to determine the contribution of red blood cells to the 31P-nuclear magnetic resonance (NMR) spectrum of the canine heart in vivo and the feasibility of measuring myocardial intracellular phosphate and pH. This was accomplished by replacing whole blood with a perfluorochemical perfusion emulsion blood substitute, Oxypherol, and noting the difference in the 31P-NMR spectrum of the heart. NMR data were collected with a NMR transmitter-receiver coil on the surface of the distal portion of the left ventricle. These studies demonstrated that a small (approximately 10%) contribution from 2,3-diphosphoglycerate (2,3-DPG) and phosphodiesters in the blood could be detected. The magnitude and shift of these blood-borne signals permitted the relative quantification of intracellular inorganic phosphate (Pi) content as well as intracellular pH. Under resting conditions, the intracellular ATP/Pi was 7.0 +/- 0.8 (n = 19). This corresponds to a free intracellular Pi content of approximately 0.8 mumol/g wet wt. The intracellular pH was 7.10 +/- 0.01 (n = 19). Acute respiratory alkalosis and acidosis, with the arterial pH ranging from approximately 7.0 to 7.7, resulted in only small changes in the intracellular pH (approximately 0.1 pH unit). These latter results demonstrate an effective myocardial intracellular proton-buffering mechanism in vivo.

Acidosis, Respiratory↗
PubMed1988

Metabolic substrate utilization by rabbit proximal tubule. An NADH fluorescence study.

The effects of various short-chain fatty acids, carboxylic acids, and amino acids on NADH fluorescence and oxygen consumption (QO2) of rabbit proximal tubule suspensions were determined. The short-chain fatty acids were the most effective substrates in increasing NADH fluorescence and QO2, followed by the carboxylic acids and amino acids. All of the substrates tested that increased NADH fluorescence proportionally increased QO2. This implies that the primary effect of these substrates was to increase QO2 by increasing the delivery of reducing equivalents to NAD and not by stimulating ATP hydrolysis directly. The relative affinity of several substrates to increase NADH fluorescence was also determined. The short-chain fatty acids had the highest affinity (10 microM range) followed by the carboxylic acids (100 microM range). These data demonstrate that the metabolic rate and NADH redox state of the renal cortical cell is very sensitive to the type of metabolic substrate available.

Amino Acids↗
PubMed1988

NMR studies of renal phosphate metabolites in vivo: effects of hydration and dehydration.

The present study characterizes the 31P-nuclear magnetic resonance (NMR) spectrum of rabbit kidneys in vivo and evaluates the effect of hydration on phosphorous metabolites including the organic solute glycerophosphorylcholine (GPC). Cortical phosphorylethanolamine is the predominant component of the phosphomonoester region of the 31P spectrum. The contribution of blood to the spectrum is mainly from 2,3 diphosphoglycerate, which comprises approximately 30% of the inorganic phosphate region. Acute infusion of 0.9% saline decreases the sodium content of the inner medulla by greater than 50% in 15 min as shown by 23Na imaging. Despite this medullary Na dilution, no change in renal GPC content was observed for greater than 1 h even with the addition of furosemide (2.5 mg/kg) or furosemide and antidiuretic hormone (0.125 U/kg). However, 20 h of chronic hydration with 0.45% saline did result in a 30% decrease in renal GPC content when compared with dehydrated animals. These findings are consistent with GPC not playing a role in the short-term regulation of the medullary intracellular milieu in response to acute reductions in medullary Na content.

2,3-Diphosphoglycerate↗
PubMed1987

Changes in pyridine nucleotide levels alter oxygen consumption and extra-mitochondrial phosphates in isolated mitochondria: a 31P-NMR and NAD(P)H fluorescence study.

Isolated rat-liver mitochondria were used to study the relation between mitochondrial NADH levels, oxygen consumption (QO2), and extra-mitochondrial phosphates. Alterations in NADH and QO2 were accomplished by incubating mitochondria with different substrates or varying amounts of exogenous ATPase while monitoring QO2 and NAD(P)H fluorescence. Two sets of conditions were studied: (1) in the presence of excess ADP and inorganic phosphate, an increase in NAD(P)H fluorescence was associated with a linear increase in QO2; (2) when QO2 was driven by the steady-state hydrolysis of ATP by exogenous ATPase, increases in QO2 were associated with proportional decreases in NAD(P)H fluorescence. For all substrates tested this relation was linear; however, the slope was substrate dependent. Different substrates were able to maintain different NAD(P)H levels at the same QO2. To investigate this further, effects of changing substrates at constant QO2 on NAD(P)H and extra-mitochondrial phosphates were determined. Addition of glutamate + malate to mitochondria respiring on citrate caused a 50% increase in NAD(P)H fluorescence, a 41% decrease in ADP, and a 30% decrease in inorganic phosphate. Similar changes for the substrate jump, pyruvate + malate to glutamate + malate were found. Finally, it was determined that a linear relation holds between increases in NAD(P)H fluorescence and increases in QO2 when substrates were varied at constant, physiologic levels of extra-mitochondrial ADP. These results indicate that QO2 depends on NAD(P)H levels as well as on extra-mitochondrial phosphates over a wide range of respiratory rates.

Adenosine Diphosphate↗
PubMed1987

Respiratory control in the glucose perfused heart. A 31P NMR and NADH fluorescence study.

The phosphate metabolites, adenosine diphosphate (ADP), inorganic phosphate (Pi), and adenosine triphosphate (ATP), are potentially important regulators of mitochondrial respiration in vivo. However, previous studies on the heart in vivo and in vitro have not consistently demonstrated an appropriate correlation between the concentration of these phosphate metabolites and moderate changes in work and respiration. Recently, mitochondrial NAD(P)H levels have been proposed as a potential regulator of cardiac respiration during alterations in work output. In order to understand better the mechanism of respiratory control under these conditions, we investigated the relationship between the phosphate metabolites, the NAD(P)H levels, and oxygen consumption (Q02) in the isovolumic perfused rat heart during alterations in work output with pacing. ATP, creatine phosphate (CrP), Pi and intracellular pH were measured using 31P NMR. Mitochondrial NAD(P)H levels were monitored using spectrofluorometric techniques. Utilizing glucose as the sole substrate, an increase in paced heart rate led to an increase in Q02 from 1.73 +/- 0.09 to 2.29 +/- 0.12 mmol Q2/h per g dry wt. No significant changes in the levels of Pi, PCr, ATP, or the calculated ADP levels were detected. Under identical conditions, an increase in heart rate was associated with a 23 + 3% increase in NAD(P)H fluorescence. Thus, under the conditions of these studies, an increase in Q02 was not associated with an increase in ADP or Pi. In contrast, increases in Q02 were associated with an increase in NAD(P)H. These data are consistent with the notion that increases in the mitochondrial NADH redox state regulate steady-state levels of respiration when myocardial work is increased.

Adenosine Diphosphate↗