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A C McLaughlin

Publications and source records attributed to A C McLaughlin.

At least 37 records · Page 2Linked to original sources
PubMed1994

Double-quantum-filtered 23Na NMR study of intracellular sodium in the perfused liver.

We acquired double-quantum-filtered 23Na NMR spectra from perfused liver, using a range of tau values from 0.2 to 24 ms, where tau is the separation between the first and second pi/2 pulses in the radio-frequency pulse sequence. For each tau value we compared the amplitude of the double-quantum-filtered 23Na NMR signal acquired from intracellular sodium ions when the liver was perfused with buffer containing the "shift reagent" Dy(PPP)2 to the amplitude of the total double-quantum-filtered 23Na NMR signal acquired when the liver was perfused with buffer containing no Dy(PPP)2. For tau < or = 4 ms, the average ratio of the two amplitudes was 0.98 +/- 0.03 (mean +/- SEM). For tau > or = 8 ms, the average ratio was significantly less than 1. These results demonstrate that double-quantum-filtered 23Na NMR signals acquired from perfused liver using short tau values arise almost exclusively from intracellular sodium ions, but double-quantum-filtered 23Na NMR signals acquired from perfused liver using long tau values contain contributions from both intracellular and extracellular sodium ions. This conclusion suggests that multiple-quantum-filtered 23Na NMR spectroscopy will be useful in studying intracellular sodium levels in the perfused liver, and possibly in the intact liver in vivo.

Animals↗
PubMed1994

Role of nitric oxide in regulating cerebrocortical oxygen consumption and blood flow during hypercapnia.

The effect of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (PaCO2 approximately 60 mm Hg and PaCO2 approximately 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety-Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect on either CMRO2 or CBF under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.

Animals↗
PubMed1994

19F magnetic resonance imaging of cerebral blood flow with 0.4-cc resolution.

19F magnetic resonance imaging techniques were used to determine "wash-in" and "wash-out" curves of the inert, diffusible gas CHF3 from 0.4-cc voxels in the cat brain, and mass spectrometer gas detection was used to determine the CHF3 concentration in expired air. These two sets of data were used to calculate cerebral blood flow values in the 0.4-cc voxels, and the blood flow images were registered with high-resolution 1H magnetic resonance images. Data were collected both during the wash-in and wash-out phases of the experiment, but the two sets of data were analyzed separately to obtain independent estimates of the blood flow during the two phases, i.e., Qin and Qout. Repeated determinations of cerebral blood flow images were performed in individual animals, and the entire protocol was repeated on five different animals. The average values of Qin and Qout for a typical 0.4-cc voxel in the parietal cortex were 83 ml 100 g-1 min-1 and 72 ml 100 g-1 min-1, respectively. Monte Carlo calculations utilizing the noise in the 19F NMR signal from this voxel predict an average standard deviation for Qin and Qout of +/- 10%. The average standard deviation for repeated measurements (in the same animal) of Qin and Qout in this voxel was +/- 14%. We conclude that 19F magnetic resonance imaging approaches have the potential to image cerebral blood flow in humans.

Animals↗
PubMed1993

Monitoring of intracellular free calcium in perfused rat liver.

Fluorescent calcium indicators have been widely used to assess cytoplasmic calcium concentration in cells. To examine the role of calcium ions on different physiological functions (e.g. in case of liver; bile secretion, glucose metabolism, etc.) there is a need for whole organ studies. We have developed a technique to estimate intracellular free calcium changes in perfused rat liver. Krebs-Henseleit perfused livers were loaded with 7 microM or 35 microM Indo-1/AM. An area 3 mm in diameter and approximately 300 microns in depth was illuminated at 340 nm. Fluorescence was monitored with photomultiplier tubes at 3 wavelengths (400 nm for Ca-bound dye, 504 nm for free dye and 464 nm for NADH). The viability of liver preparations was assessed by measurement of the concentrations of lactate dehydrogenase and alanine aminotransferase in the effluent. Loading of the livers with 7 microM Indo-1/AM via the portal vein resulted in a 5-fold increase of fluorescence at 400 nm. However the dye 'leaked' out of the liver with a half-time of 18 min. Probenecid (a specific anion carrier blocker) inhibited loss of dye in a dose dependent fashion (2.5-10 mM). Transient calcium elevations were observed in response to vasopressin (5-50 nM) at physiological levels, ethanol (0.3-0.8 M) and the calcium ionophore, ionomycin. Certain limitations were apparent with this approach: (1) it was necessary to use an anion carrier blocker to maintain a relatively steady dye concentration; (2) endogenous NADH fluorescence interfered with the calcium signal; and (3) absolute values of calcium concentration could not be determined.

Animals↗
PubMed1992

Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress.

The role of adrenal medulla-derived enkephalins in the control of hypercapnic cerebrocortical blood flow (CBF) and oxygen consumption (CMRO2) was investigated in the ketamine anesthetized rat. Three experimental interventions were utilized: inhibition of opioid receptors with naloxone, decrease of adrenal enkephalin production with chronic adrenal medullectomy, and treatment of adrenal demedullated animals with the synthetic enkephalin analog, D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAGO). In intact, untreated animals hypercapnia increased CBF and CMRO2 by approximately 300 and 35%, respectively. Naloxone reduced the hypercapnic increase of CBF, and transformed the hypercapnic increase of CMRO2 into a decrease. The mid-points of the dose-response curves for (1)-naloxone and (d)-naloxone were 10 micrograms/kg and 100 micrograms/kg, respectively. Adrenal demedullation and treatment with (1)-naloxone (0.2 mg/kg) decreased the hypercapnic CBF and CMRO2 by approximately 50%. DAGO treatment of adrenal demedullated animals restored the hypercapnic CBF and CMRO2 to values similar to those found in intact animals. These observations suggest that opioid peptides (most likely adrenal medulla-derived enkephalins) play a significant role in the regulation of CMRO2 and CBF during moderate hypercapnia.

Adrenal Medulla↗
PubMed1992

In vivo 17O NMR study of rat brain during 17O2 inhalation.

In vivo 17O NMR has been used to monitor the H2(17)O concentration in rat brain during inhalation of 17O2. The results are discussed in terms of oxygen consumption in the brain and recirculation into the brain of H2(17)O produced in other organs.

Animals↗
PubMed1991

Double-quantum surface-coil NMR studies of sodium and potassium in the rat brain.

Double-quantum filtered and conventional single-pulse sodium and potassium NMR spectra were obtained from in situ rat brain at 7.0 T. using a surface coil. In contrast to the ca. 14% decrease observed in single-pulse sodium NMR spectra upon death, increases as large as ca. 800% were observed in double-quantum filtered sodium spectra. Conversely, a ca. 26% increase was observed in single-pulse potassium spectra upon death, while double-quantum filtered potassium spectra decreased below the noise level, for the shortest preparation time used. The decay rate of double-quantum sodium coherence in the in situ rat brain after death was dependent upon the double-quantum preparation time: this behavior results from the nonuniformity of the brain, and may be related to physiological compartmentalization. The potential application to sodium NMR imaging of cerebral functionality is briefly discussed.

Animals↗
PubMed1991

In vivo measurement of cerebral oxygen consumption and blood flow using 17O magnetic resonance imaging.

We used 17O NMR imaging techniques to measure the H2(17)O concentration in a 0.8-ml voxel in the cat brain following injection of an arterial bolus of enriched H2(17)O and during inhalation of enriched 17O2. We also measured the H2(17)O concentration in arterial blood during 17O2 inhalation. The data from the first measurement were used to calculate the blood flow in the voxel. The data from all three measurements were combined to calculate the oxygen consumption in the voxel. The values of cerebral blood flow and oxygen consumption calculated with 17O NMR techniques agree reasonably well with values calculated for a similar region of the cat brain using autoradiographic techniques.

Administration, Inhalation↗
PubMed1991

Cerebral blood flow and metabolic rate in the conscious, freely moving rat: the effects of hypercapnia, and acute ethanol administration.

We propose a simple method that can be used to measure cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral glucose consumption (CMRglu) in the conscious, freely moving rat. The method is based on the classical Kety-Schmidt approach, and uses a chronic cannula in the confluens sinuum. We tested the method by investigating the response of CBF, CMRO2, and CMRglu to hypercapnia and used the approach to investigate the effects of acute alcohol administration. Severe hypercapnia (PaCO2 approximately 80 mmHg) increased the CBF by a factor of 3.5, decreased the CMRO2 by 30%, and had no significant effect on the CMRglu. Under normocapnic conditions moderate blood alcohol levels (100-200 mg%) caused no significant effects on CBF, CMRO2, or CMRglu, but high blood alcohol levels (250-400 mg%) decreased all three parameters by approximately 25%. Under hypercapnic conditions high blood alcohol levels had no effect on CBF, CMRO2, and CMRglu.

Alcoholic Intoxication↗
PubMed1990

Cerebral venous oxygen content as a measure of brain energy metabolism with increased intracranial pressure and hyperventilation.

In order to test the hypothesis that the cerebral arteriovenous oxygen difference (AVDO2) and venous oxygen content (VO2) could be used to monitor brain energy metabolism in the setting of increased intracranial pressure (ICP). 12 cats were studied with 31P-magnetic resonance spectroscopy. six cats were subjected to intracranial hypertension by cisternal infusion of saline. Energy failure occurred at an average AVDO2 of 8.4 +/- 3.2 vol% (+/- standard deviation) (range 4.7 to 14.7 vol%). The VO2 at the point of metabolic failure averaged 1.45 +/- 0.6 vol% and extended over a narrower range (1.0 to 2.9 vol%). In an additional six cats, ICP was raised to the threshold of metabolic failure and hyperventilation was then instituted (pCO2 10 to 18 torr). Five of the six cats experienced a drop in VO2 with hyperventilation. In two of these animals, hyperventilation resulted in a VO2 of 1.1 vol% or less and in metabolic failure as evidenced by a fall in phosphocreatine. It is concluded that a VO2 of less than 2 vol% is correlated with brain ischemia and that the safety of hyperventilation in the setting of increased ICP can be monitored by the use of VO2.

Animals↗
PubMed1989

Use of 19F NMR spectroscopy for measurement of cerebral blood flow: a comparative study using microspheres.

19F NMR was used to determine washout curves of an inert, diffusible gas (CHF3) from the cat brain. The cerebral blood flow was estimated from a bi- or tri-phasic fit to the deconvoluted wash-out curve, using the Kety-Schmidt approach. Cerebral blood flow values determined by 19F NMR show the expected responsiveness to alterations in Paco2, but are approximately 28% lower than cerebral blood flow values determined simultaneously by radioactive microsphere techniques. High concentrations of CHF3 have little effect on intracranial pressure, mean arterial blood pressure or Paco2, but cause small changes in the blood flow to certain regions of the brain. We conclude that 19F NMR techniques utilizing low concentrations of CHF3 have potential for the noninvasive measurement of cerebral blood flow.

Animals↗
PubMed1987

Simultaneous 31P- and 1H-nuclear magnetic resonance studies of hypoxia and ischemia in the cat brain.

The objective of this study was to evaluate simultaneous 31P/1H nuclear magnetic resonance (NMR) spectroscopy as a technique for monitoring and correlating changes in brain energy metabolism during hypoxia and ischemia. Five cats were studied with a protocol that involved 20 min of hypoxia (PaO2 20 mm), 60 min of recovery, 10 min of hypoxia with relative ischemia (bilateral carotid occlusion, PaO2 20 mm), and 60 min of recovery. Bifrontal and biparietal electrocorticograms (ECoG) were monitored continuously during the entire protocol. The results demonstrate that the degree of metabolic response is different in individual cats, but a number of quantitative relationships between metabolic parameters are consistently observed for all cats. First, there is agreement between increases in lactate and changes in intracellular pH; the observed relationship corresponds to an in vivo cerebral buffer capacity of 29 mumol/g/pH unit. Second, the delayed recovery of PCr is due to the effect of metabolic acidosis on the creatine kinase equilibrium and not to a delayed recovery of the ATP/ADP ratio. Third, the observed rate of lactate clearance from the cell is zero-order (k = 0.36 mumol/g/min) for lactate levels greater than 5 microns/g and may be composed of both lactate efflux from the cell and lactate oxidation.

Adenosine Triphosphate↗
PubMed1987

Effects of increased ICP on brain phosphocreatine and lactate determined by simultaneous 1H and 31P NMR spectroscopy.

In order to study the metabolic events surrounding ischemia induced by the graded increase of cerebrospinal fluid (CSF) pressure, the technique of simultaneous phosphorus-31- and hydrogen-1-enhanced nuclear magnetic resonance spectroscopy was applied to five cats as intracranial pressure (ICP) was gradually raised by the instillation of mock CSF. Threshold lactate rose at an average cerebral perfusion pressure (CPP) of 49 torr, and, in general, preceded a threshold decrease in phosphocreatine, which was observed at an average CPP of 29 torr. There was considerable variation among cats in the CPP at which failure of brain energy metabolism occurred, however, suggesting differences in the autoregulatory curves. It is concluded that, with elevated ICP, there is no universally "safe" CPP at which brain energy metabolism may be assumed to be uncompromised.

Animals↗
PubMed1986

An experimental test of the discreteness-of-charge effect in positive and negative lipid bilayers.

The electrostatic properties of charged bilayers and the bilayer component of biological membranes are often described theoretically by assuming the charge is smeared uniformly over the surface. This is one of the fundamental assumptions in the Gouy-Chapman-Stern (GCS) theory. However, the average distance between the charged phospholipids in a typical biological membrane is 2-3 nm, which is 2-3 times the Debye length in a 0.1 M salt solution. Existing discreteness-of-charge theories predict significant deviations from the GCS theory for the adsorption of ions to such membranes. We considered the predictions of the simplest discreteness-of-charge theory [Nelson, A. P., & McQuarrie, D. A. (1975) J. Theor. Biol. 55, 13-27], in which the charges are assumed to be fixed in a square lattice and the potential is described by the linearized Poisson-Boltzmann relation. This theory predicts deviations that are larger for counterions than for co-ions and much larger for divalent than for monovalent counterions. We tested these predictions by measuring the adsorption of a fluorescent monovalent anion and a paramagnetic divalent cation to both positive and negative membranes, which we demonstrated experimentally had the same average surface potential. All our experimental results with probes, including those obtained on membranes in the gel rather than in the liquid-crystalline state, agreed with the predictions of the GCS theory rather than with the discreteness-of-charge theory. A simple calculation indicates that the agreement between the experimental results and the predictions of the GCS theory could be due to the finite size of the lipids.

Dimyristoylphosphatidylcholine↗
PubMed1986

Ferromagnetic contrast agents: a new approach.

Most contrast agents used in NMR imaging studies to date have been paramagnetic. However, it is also possible to obtain selective contrast with a ferromagnetic agent, and these agents are potentially more sensitive than paramagnetic compounds because of their large magnetic moments. The water relaxation ability of ferromagnetic, albumin-coated magnetite (Fe3O4) particles has been investigated. These particles are quite effective at reducing both T1 and T2 at relatively low particle concentrations. The potential applications of these particles include improved visualization of the liver, gastrointestinal tract, and genitourinary tract, as well as specific targeting and detection of small tumors or other cells with unique surface receptors.

Animals↗
PubMed1986

Electrokinetic and electrostatic properties of bilayers containing gangliosides GM1, GD1a, or GT1. Comparison with a nonlinear theory.

We formed vesicles from mixtures of egg phosphatidylcholine (PC) and the gangliosides GM1, GD1a, or GT1 to model the electrokinetic properties of biological membranes. The electrophoretic mobilities of the vesicles are similar in NaCl, CsCl, and TMACl solutions, suggesting that monovalent cations do not bind significantly to these gangliosides. If we assume the sialic acid groups on the gangliosides are located some distance from the surface of the vesicle and the sugar moieties exert hydrodynamic drag, we can describe the mobility data in 1, 10, and 100 mM monovalent salt solutions with a combination of the Navier-Stokes and nonlinear Poisson-Boltzmann equations. The values we assume for the thickness of the ganglioside head group and the location of the charge affect the theoretical predictions markedly, but the Stokes radius of each sugar and the location of the hydrodynamic shear plane do not. We obtain a reasonable fit to the mobility data by assuming that all ganglioside head groups project 2.5 nm from the bilayer and all fixed charges are in a plane 1 nm from the bilayer surface. We tested the latter assumption by estimating the surface potentials of PC/ganglioside bilayers using four techniques: we made 31P nuclear magnetic resonance, fluorescence, electron spin resonance, and conductance measurements. The results are qualitatively consistent with our assumption.

Egg Yolk↗