Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy

Rasmus Stilling Tougaard; Christoffer Laustsen; Thomas Ravn Lassen; Haiyun Qi; Jakob Lykke Lindhardt; Marie Schroeder; Nichlas Riise Jespersen; Esben Søvsø Szocska Hansen; Steffen Ringgaard; Hans Erik Bøtker; Won Yong Kim; Hans Stødkilde-Jørgensen; Henrik Wiggers

doi:10.1002/mrm.28964

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy

Rasmus Stilling Tougaard, Christoffer Laustsen, Thomas Ravn Lassen, Haiyun Qi, Jakob Lykke Lindhardt, Marie Schroeder, Nichlas Riise Jespersen, Esben Søvsø Szocska Hansen, Steffen Ringgaard, Hans Erik Bøtker, Won Yong Kim, Hans Stødkilde-Jørgensen, Henrik Wiggers

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Purpose: Hyperpolarized [1- ¹³C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- ¹³C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- ¹³C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P <.001). Cardiac metabolism, measured by both hyperpolarized [1- ¹³C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO ₂/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO ₂/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- ¹³C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

Original language	English
Journal	Magnetic Resonance in Medicine
Volume	87
Issue	1
Pages (from-to)	57-69
Number of pages	13
ISSN	0740-3194
DOIs	https://doi.org/10.1002/mrm.28964
Publication status	Published - Jan 2022

Keywords

MRS
animal models of human disease
heart failure
metabolism
myocardial infarction
remodeling

Access to Document

10.1002/mrm.28964

Cite this

Tougaard, R. S., Laustsen, C., Lassen, T. R., Qi, H., Lindhardt, J. L., Schroeder, M., Jespersen, N. R., Hansen, E. S. S., Ringgaard, S., Bøtker, H. E., Kim, W. Y., Stødkilde-Jørgensen, H., & Wiggers, H. (2022). Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy. Magnetic Resonance in Medicine, 87(1), 57-69. https://doi.org/10.1002/mrm.28964

@article{950c8c89877043ad9e264fbc8729f3d3,

title = "Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy",

abstract = "Purpose: Hyperpolarized [1- 13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- 13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- 13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P <.001). Cardiac metabolism, measured by both hyperpolarized [1- 13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO 2/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO 2/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- 13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism. ",

keywords = "MRS, animal models of human disease, heart failure, metabolism, myocardial infarction, remodeling",

author = "Tougaard, {Rasmus Stilling} and Christoffer Laustsen and Lassen, {Thomas Ravn} and Haiyun Qi and Lindhardt, {Jakob Lykke} and Marie Schroeder and Jespersen, {Nichlas Riise} and Hansen, {Esben S{\o}vs{\o} Szocska} and Steffen Ringgaard and B{\o}tker, {Hans Erik} and Kim, {Won Yong} and Hans St{\o}dkilde-J{\o}rgensen and Henrik Wiggers",

note = "{\textcopyright} 2021 International Society for Magnetic Resonance in Medicine.",

year = "2022",

month = jan,

doi = "10.1002/mrm.28964",

language = "English",

volume = "87",

pages = "57--69",

journal = "Magnetic Resonance in Medicine",

issn = "0740-3194",

publisher = "John Wiley & Sons Inc.",

number = "1",

}

Tougaard, RS , Laustsen, C , Lassen, TR, Qi, H, Lindhardt, JL, Schroeder, M, Jespersen, NR , Hansen, ESS , Ringgaard, S , Bøtker, HE , Kim, WY, Stødkilde-Jørgensen, H & Wiggers, H 2022, 'Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy', Magnetic Resonance in Medicine, vol. 87, no. 1, pp. 57-69. https://doi.org/10.1002/mrm.28964

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy. / Tougaard, Rasmus Stilling ; Laustsen, Christoffer ; Lassen, Thomas Ravn et al.
In: Magnetic Resonance in Medicine, Vol. 87, No. 1, 01.2022, p. 57-69.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy

AU - Tougaard, Rasmus Stilling

AU - Laustsen, Christoffer

AU - Lassen, Thomas Ravn

AU - Qi, Haiyun

AU - Lindhardt, Jakob Lykke

AU - Schroeder, Marie

AU - Jespersen, Nichlas Riise

AU - Hansen, Esben Søvsø Szocska

AU - Ringgaard, Steffen

AU - Bøtker, Hans Erik

AU - Kim, Won Yong

AU - Stødkilde-Jørgensen, Hans

AU - Wiggers, Henrik

PY - 2022/1

Y1 - 2022/1

N2 - Purpose: Hyperpolarized [1- 13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- 13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- 13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P <.001). Cardiac metabolism, measured by both hyperpolarized [1- 13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO 2/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO 2/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- 13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

AB - Purpose: Hyperpolarized [1- 13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- 13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- 13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P <.001). Cardiac metabolism, measured by both hyperpolarized [1- 13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO 2/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO 2/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- 13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

KW - MRS

KW - animal models of human disease

KW - heart failure

KW - metabolism

KW - myocardial infarction

KW - remodeling

U2 - 10.1002/mrm.28964

DO - 10.1002/mrm.28964

M3 - Journal article

C2 - 34378800

SN - 0740-3194

VL - 87

SP - 57

EP - 69

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

IS - 1

ER -

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopy

Abstract

Keywords

Access to Document

Fingerprint

Cite this