scholarly journals Regulation of murine myocardial energy metabolism during adrenergic stress studied by in vivo 31P NMR spectroscopy

2003 ◽  
Vol 285 (5) ◽  
pp. H1976-H1979 ◽  
Author(s):  
A. V. Naumova ◽  
R. G. Weiss ◽  
V. P. Chacko
Keyword(s):  
Heart Rate ◽  
Cardiac Metabolism ◽  
High Energy ◽  
Dobutamine Stress ◽  
Resonance Spectroscopy ◽  
31P Nmr Spectroscopy ◽  
Adult Mice ◽  
The Mean ◽  
Large Animals

Image-guided, spatially localized 31P magnetic resonance spectroscopy (MRS) was used to study in vivo murine cardiac metabolism under resting and dobutamine-induced stress conditions. Intravenous dobutamine infusion (24 μg · min–1 · kg body wt–1) increased the mean heart rate by ∼39% from 482 ± 46 per min at baseline to 669 ± 77 per min in adult mice. The myocardial phosphocreatine (PCr)-to-ATP (PCr/ATP) ratio remained unchanged at 2.1 ± 0.5 during dobutamine stress, compared with baseline conditions. Therefore, we conclude that a significant increase in heart rate does not result in a decline in the in vivo murine cardiac PCr/ATP ratio. These observations in very small mammals, viz., mice, at extremely high heart rates are consistent with studies in large animals demonstrating that global levels of high-energy phosphate metabolites do not regulate in vivo myocardial metabolism during physiologically relevant increases in cardiac work.

scholarly journals Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia

2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Imaging Techniques ◽  
High Energy ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Membrane Breakdown ◽  
First Episode Schizophrenia

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.

scholarly journals Time Course of Postischemic Intracellular Alkalosis Reflects the Duration of Ischemia

1990 ◽  
Vol 10 (6) ◽  
pp. 860-865 ◽  
Author(s):  
Michael Chopp ◽  
Hua Chen ◽  
Ana M. Q. Vande Linde ◽  
Eileen Brown ◽  
K. M. A. Welch
Keyword(s):  
Specific Gravity ◽  
Brain Tissue ◽  
Cerebral Edema ◽  
Time Course ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
Ph Profile ◽  
Tissue Ph ◽  
Tissue Edema

We investigated the long-term (up to 1 week) relationships between the duration of cerebral ischemia and postischemic energy metabolic profile, pH, and tissue edema in the rat. Ten rats each were subjected to 8 or 12 min of forebrain ischemia induced by bicarotid occlusion concurrent with systemic hypotension, and the results were compared with those of 10 sham-operated rat controls. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to ischemia and at intervals up to 168 h after ischemia. Cerebral edema (measured by specific gravity) was assessed prior to ischemia and at 24, 72, and 168 h after ischemia. The data revealed significant differences in the brain tissue pH profile over time between the ischemic groups (p < 0.03). The 12-min ischemic animals exhibited brain tissue alkalosis (pH = 7.27 ± 0.12) at 24 h compared with both sham (pH = 7.09 ± 0.08) at 24 h and preischemic (pH = 7.06 ± 0.04) pH values. The pH remained alkalotic (pH = 7.23 ± 0.15) through the 48-h time period. In contrast, in the 8-min group, the onset of alkalosis was delayed until 48 h after ischemia (pH = 7.24 ± 0.15), and pH remained alkalotic for only 24 h. No difference in high-energy phosphate metabolism was detected between groups. A different time dependence of tissue pH and specific gravity changes after 12 min of ischemia was detected. The present study suggests that the duration of an ischemic event marks the time of onset of brain tissue alkalosis and its duration and that cerebral edema alone cannot explain the pH changes.

Hypoxic pHi and function modulation by Na+/H+ exchange and alpha-adrenoreceptor inhibition in heart in vivo

1997 ◽  
Vol 272 (6) ◽  
pp. H2664-H2670 ◽  
Author(s):  
M. A. Portman ◽  
Y. Xiao ◽  
B. G. Broers ◽  
X. H. Ning
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
High Energy ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Cardiac Contractile Function ◽  
Significant Drop ◽  
And Function ◽  
Phi Regulation

Regulation of intracellular pH (pHi) may contribute to maintenance of cardiac contractile function during graded hypoxia in vivo. To test this hypothesis, we disturbed pHi regulation in vivo using two approaches: alpha-adrenoreceptor antagonism with phentolamine (1 mg/kg) (Phen; n = 9); and Na+/H+ exchange inhibition with HOE-642 (2 mg/kg; n = 6) before graded hypoxia in open-chest sheep. Hemodynamic parameters including left ventricular maximal pressure development (dP/dtmax) cardiac index (CI), and left ventricular power were monitored continuously and simultaneously with high-energy phosphate levels and pHi, measured with 31P nuclear magnetic resonance spectroscopy in Phen, HOE-642, and control (Con; n = 9). In subgroups (n = 6) in Con and Phen, coronary flow, myocardial oxygen consumption (MVO2), and lactate uptake were also measured. During hypoxia, the functional parameters left ventricular dP/dtmax, CI, and left ventricular power decreased significantly compared with baseline and Con values. These decreases were preceded by a significant drop (P < 0.05) in pHi from 7.10 +/- 0.04 to 6.69 +/- 0.05 in Phen and corresponded temporally to a pHi drop from 7.10 +/- 0.02 to 6.77 +/- 0.03 in HOE-642. Decreases in pHi in Phen were not preceded by decreases in cardiac function or MVO2. In contrast, cardiac function parameters increased significantly in Con, whereas no significant pHi decrease occurred (7.07 +/- 0.03 to 6.98 +/- 0.04). We conclude that these data indicate that pHi regulation can be disrupted through alpha-adrenergic antagonism or Na+/H(+)-exchange inhibition in vivo. These studies demonstrate that pHi regulation performs a role in the modulation of cardiac function during hypoxia in vivo.

Skeletal muscle bioenergetics during frequency-dependent fatigue

1991 ◽  
Vol 260 (3) ◽  
pp. C643-C651 ◽  
Author(s):  
C. R. Bridges ◽  
B. J. Clark ◽  
R. L. Hammond ◽  
L. W. Stephenson
Keyword(s):  
Skeletal Muscle ◽  
Nmr Spectroscopy ◽  
31P Nmr ◽  
High Energy ◽  
Metabolic Energy ◽  
31P Nmr Spectroscopy ◽  
External Work ◽  
Dynamic Contractions ◽  
High Energy Phosphate Metabolism

The bioenergetic correlates of skeletal muscle fatigue were assessed in vivo with phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After surgical construction of latissimus dorsi muscle ventricles, seven beagles underwent 31P-NMR spectroscopy during 12-min exercise protocols at 25- and 85-Hz stimulation frequencies and during both isovolumetric and dynamic contractions. Exercise at 85 Hz was associated with significantly greater fatigue than exercise at 25 Hz. At both frequencies, the onset of exercise was associated with a marked increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr). As the muscle fatigued at 85 Hz but not at 25 Hz, the phosphorus spectra returned to near baseline with a decrease in Pi and increase in PCr. For a given amount of force generated, the Pi-to-PCr ratio was higher for dynamic contractions than for isovolumetric contractions. This study indicates that high-frequency fatigue is unlikely to result from the direct effects of high-energy phosphate metabolism and that contractions producing external work consume more metabolic energy than equally forceful isometric contractions.

In vivo brain phosphocreatine and ATP regulation in mice fed a creatine analog

1997 ◽  
Vol 272 (5) ◽  
pp. C1567-C1577 ◽  
Author(s):  
D. Holtzman ◽  
R. Meyers ◽  
E. O'Gorman ◽  
I. Khait ◽  
T. Wallimann ◽  
...  
Keyword(s):  
Reaction Rate ◽  
Ex Vivo ◽  
Competitive Inhibitor ◽  
High Energy ◽  
Energy Deficit ◽  
Resonance Spectroscopy ◽  
Atp Metabolism ◽  
Creatine Transport ◽  
Atp Regulation

Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, was used to study the hypothesis that the creatine-CK-phosphocreatine (PCr) system is important in regulating brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations were measured in vivo with 31P nuclear magnetic resonance spectroscopy during energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane-anesthetized mice fed GPA, creatine, or standard chow (controls). Brain phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP) concentrations were equal. The phosphagen-to-NTP ratio was lower than in controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK activity that was biochemically measured was doubled. During seizures, CK-catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or adaptive changes in ATP metabolism stabilize brain ATP and enhance survival during hypoxia in mice.

scholarly journals In vivo Magnetic Resonance Spectroscopy and its Application to Neuropsychiatric Disorders

2002 ◽  
Vol 47 (4) ◽  
pp. 315-326 ◽  
Author(s):  
Jeffrey A Stanley
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Early Stage ◽  
Neuropsychiatric Disorders ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
Membrane Phospholipids ◽  
High Energy Phosphate ◽  
Spectroscopy Studies

In vivo magnetic resonance spectroscopy (MRS) is the only noninvasive imaging technique that can directly assess the living biochemistry in localized brain regions. In the past decade, spectroscopy studies have shown biochemical alterations in various neuropsychiatric disorders. These first-generation studies have, in most cases, been exploratory but have provided insightful biochemical information that has furthered our understanding of different brain disorders. This review provides a brief description of spectroscopy, followed by a literature review of key spectroscopy findings in schizophrenia, affective disorders, and autism. In schizophrenia, phosphorus spectroscopy studies have shown altered metabolism of membrane phospholipids (MPL) during the early course of the illness, which is consistent with a neurodevelopmental abnormality around the critical period of adolescence when the illness typically begins. Children and adolescents who are at increased genetic risk for schizophrenia show similar MPL alterations, suggesting that schizophrenia subjects with a genetic predisposition may have a premorbid neurodevelopmental abnormality. Independent of medication status, bipolar subjects in the depressive state tended to have higher MPL precursor levels and a deficit of high-energy phosphate metabolites, which also is consistent with major depression, though these results varied. Further bipolar studies are needed to investigate alterations at the early stage. Lastly, associations between prefrontal metabolism of high-energy phosphate and MPL and neuropsychological performance and reduced N-acetylaspartate in the temporal and cerebellum regions have been reported in individuals with autism. These findings are consistent with developmental alterations in the temporal lobe and in the cerebellum of persons with autism. This paper discusses recent findings of new functions of N-acetylaspartate.

scholarly journals Detrimental effects of thyroid hormone analog DITPA in the mouse heart: increased mortality with in vivo acute myocardial ischemia-reperfusion

2011 ◽  
Vol 300 (2) ◽  
pp. H702-H711 ◽  
Author(s):  
M. A. Hassan Talukder ◽  
Fuchun Yang ◽  
Yoshinori Nishijima ◽  
Chun-An Chen ◽  
Lin Xie ◽  
...  
Keyword(s):  
Heart Rate ◽  
Thyroid Hormone ◽  
Myocardial Ischemia ◽  
Contractile Function ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Cardiac Metabolism ◽  
Mouse Heart ◽  
Myocardial Ischemia Reperfusion

There is emerging evidence that treatment with thyroid hormone (TH) can improve postischemic cardiac function. 3,5-Diiodothyropropionic acid (DITPA), a TH analog, has been proposed to be a safer therapeutic agent than TH because of its negligible effects on cardiac metabolism and heart rate. However, conflicting results have been reported for the cardiac effects of DITPA. Importantly, recent clinical trials demonstrated no symptomatic benefit in patients with DITPA despite some improved hemodynamic and metabolic parameters. To address these issues, dose-dependent effects of DITPA were investigated in mice for baseline cardiovascular effects and postischemic myocardial function and/or salvage. Mice were treated with subcutaneous DITPA at 0.937, 1.875, 3.75, or 7.5 mg·kg−1·day−1 for 7 days, and the results were compared with untreated mice for ex vivo and/or in vivo myocardial ischemia-reperfusion (I/R). DITPA had no effects on baseline body temperature, body weight, or heart rate; however, it mildly increased blood pressure. In isolated hearts, baseline contractile function was significantly impaired in DITPA-pretreated mice; however, postischemic recovery was comparable between untreated and DITPA-treated groups. In vivo baseline cardiac parameters were significantly affected by DITPA, with increased ventricular dimensions and decreased contractile function. Importantly, DITPA-treated mice demonstrated high prevalence of fatal cardiac rhythm abnormalities during in vivo ischemia and/or reperfusion. There were no improvements in myocardial infarction and postischemic fractional shortening with DITPA. Myocardial sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and heat shock protein (HSP) levels remained unchanged with DITPA treatment. Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.

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