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

Magn Reson Med. 2022 Jan;87(1):57-69. doi: 10.1002/mrm.28964. Epub 2021 Aug 11.

Abstract

Purpose: Hyperpolarized [1-13 C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1-13 C]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 [1-13 C]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 [1-13 C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO2 /pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO2 /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 [1-13 C]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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Heart Failure* / diagnostic imaging
  • Heart Failure* / drug therapy
  • Magnetic Resonance Spectroscopy
  • Myocardial Infarction* / diagnostic imaging
  • Myocardial Infarction* / drug therapy
  • Myocardium
  • Pyruvic Acid
  • Rats
  • Stroke Volume
  • Ventricular Function, Left

Substances

  • Pyruvic Acid