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Biomedical subjects

R L Nunnally

Publications and source records attributed to R L Nunnally.

At least 37 records · Page 2Linked to original sources
PubMed1988

Hypotonia of rickets: a sequential study by P-31 magnetic resonance spectroscopy.

To address the role of high-energy phosphorus compounds in the hypotonia of vitamin D-dependent rickets, nuclear magnetic resonance spectra were obtained sequentially from resting gastrocnemius muscle of a 10-month-old infant with rachitic hypotonia during supplementation with vitamin D, calcium, and phosphorus. During the initial weeks of treatment, the hypotonia resolved before evidence of epiphyseal mineralization. Over the early treatment period, the muscle phosphocreatine/beta-adenosine triphosphate [PCr/beta-ATP] ratio increased from 2.7-2.8 [wk 1-2] to 3.9-4.5 [wk 7-9]. The PCr/beta-ATP ratio for 6-month-old normal infant gastrocnemius and adult forearm were 4.0 and 5.7, respectively. Muscle strength appeared to recover concomitantly with an increase in retained muscle phosphorus and high-energy phosphate compounds, and with relative increase in the muscle phosphocreatine to ATP ratio. The synchrony of clinical recovery may relate to the recovery kinetics of these metabolic changes.

Adenosine Triphosphate↗
PubMed1987

Characterization of the 31P nuclear magnetic resonance spectrum from human melanoma tumors implanted in nude mice.

31P nuclear magnetic resonance spectra of human melanoma (BRO) cells implanted in nude mice were obtained both in vitro and in vivo. The tumors were allowed to grow in the right axillary region of six adult Swiss nude mice to a transverse diameter of 1.5-2 cm, at which point the in vivo 31P nuclear magnetic resonance spectra were obtained. The animals were subsequently sacrificed and the tumor perchloric acid extract was studied in vitro. Relative peak areas are comparable in the two experiments with the exception of inorganic phosphate, which is more abundant in vivo than in vitro by a factor of 4. This difference may be attributed to a greater contribution of the necrotic portion of the tumor to the in vivo spectra. Resonance peaks in the spectrum of the extract were identified on the basis of their coincidence with standards added at pH 7 and 10. Non-energy phosphorylated metabolites present in the tumor at high levels include phosphoethanolamine, phosphocholine, glycerol phosphocholine, and uridine-5'-diphospho-N-acetyl glucosamine. Sugar phosphates and 2,3-diphosphoglycerate from blood made minor contributions to the spectrum. The tumor also contained substantial amounts of pyrimidine triphosphates accounting for 34% of the total nucleoside triphosphate pool.

Animals↗
PubMed1987

High-energy phosphates and function in isolated, working rabbit hearts.

An isolated, working, rabbit heart has been developed for use with nuclear magnetic resonance (NMR) spectroscopy. This model is functionally stable over a 4-h period and displays classic hemodynamic responses to work-load changes. Control 31P spectra of this preparation (n = 5) were obtained with simultaneous recordings of left ventricular pressure (LVP), LVP differentiated with respect to time (dP/dt), heart rate (HR), and cardiac output (CO). ATP, phosphocreatine (PCr), and hemodynamics remained stable over a 90-min perfusion. Hearts were also subjected to 13.5 min of global ischemia (IS) at 37 degrees C followed by 60 min of reperfusion (RE, n = 7) or 45 min of chronic IS (n = 6). Contraction ceased within 60 s of IS. PCr loss was rapid, reaching undetectable limits by 11 min. ATP loss was gradual and bore no relationship to functional loss. ATP fell to 60 +/- 4% (means +/- SE) of pre-IS levels after 13.5 min of IS. With RE, PCr returned to control levels, whereas ATP values remained depressed for the entire 60 min. Functional activity resumed with RE, but dP/dt did not rise above 85 +/- 7% of preischemic values. No correlation between residual ATP at the end of IS and functional recovery during RE was evident.

Adenosine Triphosphate↗
PubMed1987

The use of the chemical shift of the phosphomonoester P-31 magnetic resonance peak for the determination of intracellular pH in the brains of neonates.

The use of the chemical shift of the phosphomonoester P-31 magnetic resonance peak for the determination of intracellular pH has been assessed for piglet and neonatal human brain in vivo. The chemical shift difference between resonance peaks corresponding to phosphoethanolamine and inorganic phosphate, compared with phosphocreatine, was determined for piglets and human neonates. Using in vitro pH titration data to calculate intracellular pH, it was found that pH values from the phosphoethanolamine peak (pH 6.84 to 6.80) were lower than pH estimates from the inorganic phosphate peak (pH 7.22 to 6.99). This difference suggests that phosphoethanolamine and inorganic phosphate may exist in different intracellular environments. Results are presented to demonstrate that the phosphomonoester peak may also be used to measure changes in intracellular pH associated with brain ischemia.

Animals↗
PubMed1986

Improved in vivo magnetic resonance imaging of acute myocardial infarction after intravenous paramagnetic contrast agent administration.

Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), a paramagnetic relaxation agent, has been used in vitro to improve the detection of acute myocardial infarction (MI) by magnetic resonance imaging (MRI). In this study, the ability of Gd-DTPA to improve in vivo magnetic resonance imaging of MI was examined. Ten dogs with MI caused by left anterior descending coronary artery ligation were imaged 1 to 5 days after infarction. Imaging was performed before and for 2 hours after intravenous administration of 0.34 mmol/kg Gd-DTPA. One to 2 days after MI, Gd-DTPA improved visualization of the infarct in 3 of 4 dogs. This effect was more prominent in dogs imaged 4 to 5 days after MI, when 6 of 6 dogs showed substantially improved infarct definition after Gd-DTPA. At both times the intensity ratio, an objective measure of contrast between infarcted and normal tissue that is defined by the ratio of image intensity of infarcted area to that of noninfarcted area, was significantly better after Gd-DTPA administration. The intensity ratio at 24 to 48 hours after infarction was 1.4 +/- 0.2 (mean +/- standard deviation) before Gd-DTPA, and 1.7 +/- 0.6 after Gd-DTPA (p = 0.03). The intensity ratio at 4 to 5 days after infarction was 1.5 +/- 0.3 before Gd-DTPA, and 1.8 +/- 0.5 after Gd-DTPA (p less than 0.001). Thus, Gd-DTPA administration improves in vivo visualization of MI by MRI.

Animals↗
PubMed1986

Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity.

Previous studies have suggested that one of the mechanisms of adriamycin (ADR) cardiomyopathy is depletion of high-energy phosphate stores (HEP). To examine this hypothesis, we used 31P nuclear magnetic resonance to assess the adenosine triphosphate-to-phosphocreatine ratio (ATP-to-PCr ratio) in Langendorff-perfused rabbit hearts. Using either an acute (5 days of therapy at 5 mg/kg/day) or chronic model (7 to 10 weeks of therapy at 1.2 or 1.5 mg/kg twice a week), we compared isovolumetric LV systolic pressure, heart rate, ATP-to-PCr ratios, and histologic lesions between the treated and control animals in each model. In the acute model, there was a significant increase in the ATP-to-PCr ratio (P less than 0.02), without significant changes in myocardial function. Despite significant hemodynamic and histologic alterations in the chronic model, compared to controls, we were unable to identify significant differences in ATP-to-PCr ratios. We conclude that there appear to be differences in energy metabolism between the acute cardiotoxicity and the chronic cardiomyopathy of ADR in the rabbit model and the mechanism of the chronic cardiomyopathy from ADR therapy does not appear to be related to progressive impairment of cellular high-energy phosphate metabolism as measured by the ATP-to-PCr ratio.

Adenosine Triphosphate↗
PubMed1986

Magnetic resonance imaging of acute myocardial infarction: gadolinium diethylenetriamine pentaacetic acid as a marker of reperfusion.

We examined the effects of a paramagnetic contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) on magnetic resonance images of acute myocardial infarction with and without reperfusion. Twenty-two dogs underwent occlusion of the left anterior descending coronary artery (LAD). In 10 dogs (group I) the LAD remained occluded for 3 hr and in the other 12 (group II) for 2 hr followed by 1 hr of reperfusion. Gd-DTPA (0.34 mM/kg) was administered to five dogs in group I at 2 hr and 5 min after occlusion and to seven dogs in group II 5 min after reperfusion. At 3 hr after ligation, the hearts were excised and imaged with spin echo and inversion recovery pulse sequences on a 0.35 Tesla magnetic resonance imager. Reperfused hearts given Gd-DTPA demonstrated a significant increase in contrast between normal and reperfused myocardium as compared with nonreperfused hearts and reperfused hearts not given Gd-DTPA. This enhancement was particularly prominent in the inversion recovery images. Studies performed in vivo in two additional dogs demonstrated similar enhancement with reperfusion with Gd-DTPA in gated spin echo images. Contrast-enhanced magnetic resonance imaging allows the detection of reperfusion early in the course of acute infarction.

Animals↗
PubMed1985

Metabolic studies of pyruvate- and lactate-perfused guinea pig hearts by 13C NMR. Determination of substrate preference by glutamate isotopomer distribution.

Guinea pig hearts perfused in vitro with 99% enriched [3-13C]pyruvate and [3-13C]lactate have been examined by 13C NMR spectroscopy at 75.45 MHz. Resonances from the intracellular metabolites, glutamate, aspartate, alanine, citrate, malate, lactate, and acetylcarnitine are detected in the [3-13C]pyruvate-perfused hearts while glutamate is the only metabolite observed in the [3-13C]lactate-perfused hearts. Extracts obtained from individual freeze-clamped hearts run under high resolution conditions show similar distributions of metabolites indicating that the intracellular concentrations of these metabolites are indeed quite dependent upon the substrate being utilized. The excellent signal to noise in the spectra of lactate-perfused hearts allows observation of spin-spin coupling between 13C-enriched nuclei in the various glutamate isotopomers within the intact heart. It is shown that the steady-state distribution of glutamate isotopomers is determined by the amount of 12C- versus 13C-enriched acetyl-CoA entering the citric acid cycle and this provides the basis for a direct determination of substrate utilization by the heart in the presence of competing substrates. Similar information may be derived from the 13C spectrum of an extract prepared from a single [3-13C]pyruvate-perfused heart. Our results indicate that lactate is preferred over glucose by the guinea pig heart even in the presence of insulin.

Acetyl Coenzyme A↗
PubMed1985

Fluorine-19 NMR spectroscopy and imaging investigations of myocardial perfusion and cardiac function.

Fluorine-19 nuclear magnetic resonance images of rabbit hearts have been obtained with the administration of a fluorinated contrast compound. The use of fluorine-labeled compounds allows differences in tissue perfusion to be demonstrated between hearts with and without coronary artery ligation. In postischemic reperfusion studies, regional hypoperfusion is also demonstrated by 19F imaging. The results of in vivo rabbit studies show that 19F NMR can be used to monitor the rate of blood pool and extravascular space dilution of a single bolus injection of either a water soluble or emulsified fluorine-labeled agent.

Animals↗
PubMed1985

Muscle fatigue in McArdle's disease studied by 31P-NMR: effect of glucose infusion.

In muscle phosphorylase deficiency (McArdle's disease) there is an abnormally rapid fatigue during strenuous exercise. Increasing substrate availability to working muscle can improve exercise tolerance but the effect on muscle energy metabolism has not been studied. Using phosphorus-31 nuclear magnetic resonance (31P-NMR) we examined forearm muscle ATP, phosphocreatine (PCr), inorganic phosphate (Pi) and pH in a McArdle patient (MP) and two healthy subjects (HS) at rest and during intermittent maximal effort handgrip contractions under control conditions (CC) and during intravenous glucose infusion (GI). Under CC, MP gripped to impending forearm muscle contracture in 130 s with a marked decline in muscle PCr and a dramatic elevation in Pi. During GI, MP exercised easily for greater than 420 s at higher tensions and with attenuated PCr depletion and Pi accumulation. In HS, muscle PCr and Pi changed more modestly and were not affected by GI. In MP and HS, ATP changed little or not at all with exercise. The results suggest that alterations in the levels of muscle PCr and Pi but not ATP are involved in the muscle fatigue in McArdle's disease and the improved exercise performance during glucose infusion.

Adenosine Triphosphate↗
PubMed1985

Magnetic resonance demonstration of multiple sclerosis plaques in the cervical cord.

Magnetic resonance imaging (MRI) has been shown to be far more sensitive than computed tomography (CT) in the detection of multiple sclerosis plaques within the brain. Unlike CT, MRI is also able to detect multiple sclerosis in the brainstem and cerebellum. This report is the first description of MRI of multiple sclerosis plaques within the cervical spinal cord. Twenty-one patients with clinically typical multiple sclerosis had characteristic plaques within the brain. In 10 patients one or more plaques were identified in the cervical spinal cord. Plaques in the spinal cord were detected only in the upper cervical region using the 30-cm head radiofrequency coil. No lesions were identified using the larger-diameter body coil because of poorer signal-to-noise ratio. Further improvement in visualization of plaques in the lower cervical and thoracic spinal cord may depend on development of high-quality surface coils.

Brain↗
PubMed1983

In vivo monitoring of metabolism with nuclear magnetic resonance spectroscopy.

At the present time, there is no proven clinically useful method of directly and noninvasively assessing the metabolic competence of an injured site within the body. Progress in the field of in vivo nuclear magnetic resonance (NMR) spectroscopy has been occurring at a rapid pace in the past decade and offers considerable promise of supplying this previously unavailable information. Phosphorus-31 and carbon-13 are the two spectra that have been studied most extensively up to this point in time.

Animals↗
PubMed1983

Response of 31P-nuclear magnetic resonance spectra of frog skin to variations in PCO2 and hypoxia.

31P-nuclear magnetic resonance (NMR) studies were conducted on split epithelial sheets of frog skins to examine the effects of hypoxia and respiratory pH variations on various phosphate-containing intracellular substrates. Frog skins were split into epithelial sheets from which the supporting tissue was removed. Epithelial sheets in either phosphate-free Cl--Ringer or phosphate-free SO2-4-Ringer were bubbled at room temperature with 100% N2, 100% O2, 2% CO2-98% O2, 5% CO2-95% O2, and 15% CO2-85% O2. The results show that the intracellular pH (pHi) with Cl- -Ringer was 7.19 and with SO2-4-Ringer was 7.42 with extracellular pH of 7.52 when bubbled with 100% O2. These pHiS indicate that H+ concentration is at least an order of magnitude less than predicted from the previously measured Nernst potential. With exposure to increasing extracellular PCO2, there is a polynomial decrease in pHi. The pHi tended to be more alkaline in SO2-4 -Ringer, suggesting the presence of a HCO-3/Cl- exchange mechanism. The ATP concentration is critically and reversibly dependent on PO2. ADP concentrations were consistently low in well-oxygenated conditions. Variable but small quantities of phosphocreatine were detected. These studies demonstrate further the potential importance in utilizing NMR spectroscopy to examine coupling of biochemical substrates to epithelial transport processes.

Animals↗
PubMed1981

Assessment of pharmacological treatment of myocardial infarction by phosphorus-31 NMR with surface coils.

Phosphorus-31 nuclear magnetic resonance (NMR) measurements with small surface coils have been used to observe phosphorus metabolism of perfused hearts within localized regions. The method allows for direct, noninvasive, sequential assessment of the altered regional metabolism resulting from myocardial infarction and its response to drug treatment, which cannot be observed by conventional techniques.

Animals↗
PubMed1979

Adenosine triphosphate compartmentation in living hearts: a phosphorus nuclear magnetic resonance saturation transfer study.

31P nuclear magnetic resonance (NMR) studies of creatine phosphokinase (CPK) kinetics using saturation transfer techniques are reported. The phosphocreatine (PCr) and adenosine triphosphate (ATP) levels in perfused hearts can be altered experimentally by stopping the flow of perusate (ischemia) to the heart for 35-min periods, followed by reperfusion to produce stable levels of performance. Utilization of energy by the heart was altered by administration of 25 mM potassium chloride (KCl) in the perfusate, which arrests contraction of the myocardium. Compared with control heart studies, the unidirectional rates measured during ischemia and KCl arrest are altered. The rates observed in the control experiments indicate that the CPK system is not in a steady state. This apparent deviation from steady-state conditions is ascribed to the existence of intracellular compartmentation of ATP.

Adenosine Triphosphate↗