Analysis of rat heart in vivo by phosphorus nuclear magnetic resonance.

Grove, Thomas H.; Ackerman, Joseph J. H.; Radda, George K.; Bore, Peter J.

doi:10.1073/pnas.77.1.299

Cited by 109 publications

(33 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This method has better spatial resolution than the depth-selection protocol (the resolution is -5 mm). The values of the PCr/ATP ratio obtained for the adult human myocardium are very close to those reported for animal hearts in vivo (4,5). We realize that without cardiac cycle gating, the values represent an average over all cycles of the heart.…”

Section: J)supporting

confidence: 61%

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

Blackledge¹,

Rajagopalan²,

Oberhaensli³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

View full text Add to dashboard Cite

We have developed 31P NMR spectroscopic methods to determine quantitatively relative levels of phosphorous-containing metabolites in the human myocardium. We have used localization techniques based on the rotating-frame imaging experiment and carried out with a double-surface coil probe. Information is obtained from selected slices by rotatingframe depth selection and from a complete one-dimensional spectroscopic image using phase-modulated rotating-frame imaging. The methods collect biochemical information from metabolites in human heart, and we use the fact that the phosphocreatine/ATP molar ratio in skeletal muscle at rest is higher than that in working heart to demonstrate that localization has been achieved for each investigation. The phosphocreatine/ATP molar ratio in normal human heart has been measured as 1.55 ± 0.20 (mean + SD) (3.5-sec interpulse delay) in six subjects using depth selection and as 1.53 ± 0.25 (mean + SD) in four subjects using spectroscopic imaging. Measurement of this ratio is expected to give a useful and reproducible index of myocardial energetics in normal and pathological states.It has been shown that 31P NMR spectroscopy provides a useful insight into myocardial energetics using isolated and perfused rat hearts (1-3). In particular, the relative concentrations of phosphocreatine (PCr), ATP, and Pi, as well as intracellular pH, can yield information about the relationship between ATP supply and demand and give insight into metabolic control. It has also been shown that 31P NMR spectra from the hearts of live rats were qualitatively similar to those of the isolated perfused organ, but differed quantitatively in that the PCr/ATP molar ratio was 30% higher in vivo than for the isolated heart (4). A similarly high PCr/ATP molar ratio of 1.7 was observed in the canine heart, by using a catheter coil, which removed the necessity for surgery (5).The first spectroscopic investigation of human heart was performed on infants, where localization was achieved by simply using a surface coil probe. A PCr/ATP molar ratio of 2.0 ± 0.1 was reported in a healthy 18-month-old child compared to a lower value of 1.3 in an 8-month-old child with cardiomegaly (6). In contrast, using depth-resolved spectroscopy, the PCr/ATP molar ratio was found to be 1.3 ± 0.4 in a single adult (7). Accurate, rapid, and reproducible measurements of PCr/ATP ratio will be essential in the investigation of human heart disease by 31P NMR. The development of differential localization techniques have made such measurements theoretically possible in human subjects (8)(9)(10)(11)(12).The specific problems associated with investigating the human heart using 31P NMR include the achievement of adequate spatial localization and establishment of objective criteria to ensure that the data obtained are representative of cardiac muscle. Any contamination by a signal from overlying skeletal muscle will distort the measured PCr/ATP ratio, as studies show that this ratio in skeletal muscle is very different from that in cardiac mu...

show abstract

Section: J)supporting

confidence: 61%

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

Blackledge¹,

Rajagopalan²,

Oberhaensli³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

View full text Add to dashboard Cite

show abstract

“…To this aim, 31p-NMR spectra were collected before and after turning off the ventilator and clamping the ventilator tubes. Phosphocreatine fell to 50% of its initial value in 5-10 min, which is within the range of values published by others for cardiac muscle phosphocreatine under comparable conditions [21,22]. Skeletal muscle phosphocreatine is known to be considerably less rapidly utilized following death of the animal.…”

Section: -U P-nmr Of Heart In Control Ratssupporting

confidence: 67%

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

Nicolay¹,

Aue

Seelig

et al. 1987

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

In vivo 31p-NMR was used to measure the effects of the anti-tumor drug adriamycin on the energy metabolism of rat heart. The exclusive acquisition of NMR signal from cardiac muscle was assured by positioning a solenoidal radio-frequency NMR coil around the heart. Appropriate control experiments verified that 31p-NMR spectra solely originated from this organ. Acute effects occurring shortly after adriamycin administration are expressed in 31p spectra as a dose-dependent decline in the cardiac levels of phosphocreatine, after which stabilization at a new steady-state level occurs. These acute effects of a single dose are complete in 30-60 min and no significant further changes take place within 150 min after drug introduction. Longer-term effects of single high doses and of multiple lower doses were measured up to a week after the initiation of treatment. It seemed that at a total dose of 20 mg/kg, drug-induced interference with cardiac energy metabolism was more pronounced than at the same dose in the acute phase. These 31p-NMR data demonstrate that adriamycin treatment is accompanied by a decrease of the cardiac phosphocreatine/ATP ratio which might be an expression of the well-established cardiotoxicity of the drug.

show abstract

“…17 " However, pathways of carbon metabolism are centrally involved in the production of energy, and the ability to observe these by I3 C NMR greatly extends the power of NMR to study metabolism. We report here the use of I3 C and 3I P NMR spectroscopy to correlate in time the metabolism of labeled carbon metabolites with changes in high energy phosphorus metabolites and pH during ischemia and reflow in the isolated Langendorff-perfused guinea pig heart.…”

Section: I P Nuclear Magnetic Resonance Studymentioning

confidence: 99%

Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study.

Hoekenga

Brainard

Hutson

1988

Circulation Research

View full text Add to dashboard Cite

The effects of 11.7 mM glucose, insulin, and potassium (GIK) on metabolism during ischemia were investigated in the perfused guinea pig heart using magnetic resonance spectroscopy. Intracellular metabolites, primarily glycogen and glutamate, were labeled with I3 C by addition of [l-13 C]glucose to the perfusate during a normoxk, preischemic period. 13C and 31 P NMR spectroscopy was used to observe the metabolism of "C-labeled metabolites simultaneously with high-energy phosphorus metabolites and pH. The extent of acidosis and the rate and amount of labeled lactate accumulation during ischemia were the same in control (3 mM glucose + insulin) and GIK-treated hearts. In contrast, the rate of labeled glycogen mobilization during ischemia in GIK-treated hearts was one third the rate observed in control hearts. These observations suggest that GIK decreased the rate of glycogenolysis during ischemia without affecting the rate of glycolysis. We propose that glucose contributed as a glycolytic substrate to a greater extent during ischemia in GIK-treated hearts than in hearts perfused with 3 mM glucose and insulin. The glycogen-sparing effect of GIK demonstrated in these studies could delay the onset of ischemic damage in a clinical setting by prolonging the availability of glycolytic substrate necessary for production of high-energy phosphate. (Circulation Research 1988;62:1065-1074 M yocardial ischemia is a common and important clinical problem. Although metabolism of the ischemic myocardium has been an area of active investigation for many years, the metabolic changes resulting from the inadequate oxygen and substrate supply and product removal associated with ischemia are incompletely understood. However, it is clear that one of the important metabolic events leading to cellular damage during ischemia is failure of the rate of energy production to meet the demands for energy utilization.Several therapeutic strategies have been introduced to alter cardiac metabolism during ischemia. A mixture of glucose, insulin, and potassium (GIK) was initially used 25 years ago as a means of eliminating the electrocardiographic abnormalities of myocardial infarction.1 Since that time GIK has been used in numerous studies of coronary artery occlusion in animals and man. Nearly all of the animal studies, using a variety of measures of recovery, have shown reduced infarct size and improved tissue metabolism.2 " 3 Studies in man have been less conclusive. Infusion of GIK in patients Received November 6, 1986; accepted January 6, 1988. with acute myocardial infarction has resulted in improved left ventricular function, 6 improved electrical stability, 7 clinical improvement, 8 and reduced mortality. 9 Other studies have found no reduction in mortality.l 0 " In patients with stable angina pectoris and coronary artery disease, administration of GIK, together with cardiac pacing, was beneficial in some studies 12 and detrimental in others.13M A better understanding of the metabolic action of GDC may explain many of these contradicto...

show abstract

Analysis of rat heart in vivo by phosphorus nuclear magnetic resonance.

Cited by 109 publications

References 29 publications

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

Rates of glycolysis and glycogenolysis during ischemia in glucose-insulin-potassium-treated perfused hearts: A 13C, 31P nuclear magnetic resonance study.

Contact Info

Product

Resources

About