scholarly journals Abnormal energetics and ATP depletion in pressure-overload mouse hearts: in vivo high-energy phosphate concentration measures by noninvasive magnetic resonance

2009 ◽  
Vol 297 (1) ◽  
pp. H59-H64 ◽  
Author(s):  
Ashish Gupta ◽  
V. P. Chacko ◽  
Robert G. Weiss

31P magnetic resonance spectroscopy (MRS) offers a unique means to noninvasively quantify the major cardiac high-energy phosphates, creatine phosphate (PCr) and adenosine 5′-triphosphate (ATP), that are critical for normal myocardial contractile function and viability. Spatially localized 31P MRS has been used to quantify the in vivo PCr-to-ATP ratio (PCr/ATP) of murine hearts, including those with pressure-overload hypertrophy induced by thoracic aortic constriction (TAC). To date, there has been no approach for measuring the absolute tissue concentrations of PCr and ATP in the in vivo mouse heart that promise a better understanding of high-energy metabolism. A method to quantify in vivo murine myocardial concentrations of PCr and ATP using an external reference is described, validated, and applied to normal and TAC hearts. This new method does not prolong the scan times in mice beyond those previously required to measure PCr/ATP. The new method renders an [ATP] of 5.0 ± 0.9 (mean ± SD) and [PCr] of 10.4 ± 1.4 μmol/g wet wt in normal mouse hearts ( n = 7) and significantly lower values in TAC hearts ( n = 10) of 4.0 ± 0.8 and 6.7 ± 2.0 μmol/g wet wt for [ATP] ( P < 0.04) and [PCr] ( P < 0.001), respectively. The in vivo magnetic resonance [ATP] results are in good agreement with those obtained using an in vitro enzyme luminescent assay of perchloric acid extracts of the same hearts. In conclusion, a validated 31P MRS method for quantifying [ATP] and [PCr] in the in vivo mouse heart using spatial localization and an external reference is described and used to demonstrate significant reductions in not only PCr/ATP but [ATP] in hypertrophied TAC hearts.

2020 ◽  
Vol 32 (1) ◽  
pp. 229-237
Author(s):  
Guillaume Chazot ◽  
Sandrine Lemoine ◽  
Gabriel Kocevar ◽  
Emilie Kalbacher ◽  
Dominique Sappey-Marinier ◽  
...  

BackgroundThe precise origin of phosphate that is removed during hemodialysis remains unclear; only a minority comes from the extracellular space. One possibility is that the remaining phosphate originates from the intracellular compartment, but there have been no available data from direct assessment of intracellular phosphate in patients undergoing hemodialysis.MethodsWe used phosphorus magnetic resonance spectroscopy to quantify intracellular inorganic phosphate (Pi), phosphocreatine (PCr), and βATP. In our pilot, single-center, prospective study, 11 patients with ESKD underwent phosphorus (31P) magnetic resonance spectroscopy examination during a 4-hour hemodialysis treatment. Spectra were acquired every 152 seconds during the hemodialysis session. The primary outcome was a change in the PCr-Pi ratio during the session.ResultsDuring the first hour of hemodialysis, mean phosphatemia decreased significantly (−41%; P<0.001); thereafter, it decreased more slowly until the end of the session. We found a significant increase in the PCr-Pi ratio (+23%; P=0.001) during dialysis, indicating a reduction in intracellular Pi concentration. The PCr-βATP ratio increased significantly (+31%; P=0.001) over a similar time period, indicating a reduction in βATP. The change of the PCr-βATP ratio was significantly correlated to the change of depurated Pi.ConclusionsPhosphorus magnetic resonance spectroscopy examination of patients with ESKD during hemodialysis treatment confirmed that depurated Pi originates from the intracellular compartment. This finding raises the possibility that excessive dialytic depuration of phosphate might adversely affect the intracellular availability of high-energy phosphates and ultimately, cellular metabolism. Further studies are needed to investigate the relationship between objective and subjective effects of hemodialysis and decreases of intracellular Pi and βATP content.Clinical Trial registry name and registration number Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy (CIPHEMO), NCT03119818


Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.


2007 ◽  
Vol 292 (1) ◽  
pp. H387-H391 ◽  
Author(s):  
M. Y. Maslov ◽  
V. P. Chacko ◽  
M. Stuber ◽  
A. L. Moens ◽  
D. A. Kass ◽  
...  

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 ± 4 vs. 140 ± 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 ± 3 vs. 61 ± 8 μl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 ± 4 vs. 38 ± 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 ± 0.1 vs. 1.3 ± 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 ± 26 vs. 167 ± 36 mg; P < 0.01) and cavity size (EDV: 61 ± 8 vs. 76 ± 8 μl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.


2002 ◽  
Vol 47 (4) ◽  
pp. 315-326 ◽  
Author(s):  
Jeffrey A Stanley

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.


1988 ◽  
Vol 8 (6) ◽  
pp. 816-821 ◽  
Author(s):  
Kathryn Allen ◽  
Albert L. Busza ◽  
H. Alan Crockard ◽  
Richard S. J. Frackowiak ◽  
David G. Gadian ◽  
...  

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. At the same time, intracellular pH and the concentrations of lactate and high-energy phosphates were measured in the brain using 1H and 31P nuclear magnetic resonance spectroscopy. Flow and metabolism have been followed during either a 15- or a 30-min ischaemic period (induced by bilateral carotid occlusion) and for up to 1 h of recovery. There was no significant difference between the flow characteristics of the two experimental groups. High-energy phosphate levels and pH returned to control within ∼20 min of the end of the ischaemic period. Lactate clearance, following a 30-min occlusion, was slower than the recovery of pH. The concentration of free ADP, calculated from the creatine kinase equilibrium, was lower during the recovery phase than under control conditions.


1999 ◽  
Vol 58 (4) ◽  
pp. 841-850 ◽  
Author(s):  
Chris Boesch ◽  
Jacques Décombaz ◽  
Johannes Slotboom ◽  
Roland Kreis

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are being increasingly used for investigations of human muscle physiology. While MRI reveals the morphology of muscles in great detail (e.g. for the determination of muscle volumes), MRS provides information on the chemical composition of the tissue. Depending on the observed nucleus, MRS allows the monitoring of high-energy phosphates (31P MRS), glycogen (13C MRS), or intramyocellular lipids (1H MRS), to give only a few examples. The observation of intramyocellular lipids (IMCL) by means of 1H MRS is non-invasive and, therefore, can be repeated many times and with a high temporal resolution. MRS has the potential to replace the biopsy for the monitoring of IMCL levels; however, the biopsy still has the advantage that other methods such as those used in molecular biology can be applied to the sample. The present study describes variations in the IMCL levels (expressed in mmol/kg wet weight and ml/100 ml) in three different muscles before and after (0, 1, 2, and 5 d) marathon runs for a well-trained individual who followed two different recovery protocols varying mainly in the diet. It was shown that the repletion of IMCL levels is strongly dependent on the diet post exercise. The monitoring of IMCL levels by means of 1H MRS is extremely promising, but several methodological limitations and pitfalls need to be considered, and these are addressed in the present review.


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