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Imaging myocardial metabolism and ischemic memory

Abstract

The advent of myocardial metabolic imaging more than 30 years ago ushered in a paradigm shift in the clinical management of patients with ischemic and nonischemic heart disease. A classic example is the so-called metabolic memory of altered glucose and fatty acid metabolism in regions of myocardial ischemia and reperfusion. At the cellular level, metabolic memory is driven by changes in the activities and expression of a host of metabolic enzymes, including reactivation of the fetal gene program. The future of metabolic imaging will require a more-refined understanding of the pathways of metabolic adaptation and maladaptation of the heart. Recent evidence suggests that metabolic signals alter metabolic fluxes and give rise to specific metabolic patterns that, in turn, lead to changes in translational and/or transcriptional activities in the cardiac myocyte. In other words, metabolism provides a link between environmental stimuli and a host of intracellular signaling pathways. This concept has not yet been fully explored in vivo, although metabolic adaptation represents the earliest response to myocardial ischemia and left ventricular remodeling.

Key Points

  • Imaging of energy-providing pathways during and after an episode of myocardial ischemia might provide important insights into the pathophysiology of coronary artery disease

  • Designing metabolic imaging modalities that take into account the complexities of the pathways of energy transfer remains a challenge

  • While the normal heart readily mobilizes its metabolic reserve, metabolism is dysregulated in the failing heart and the myocardium is less responsive to inotropic stimulation

  • Nuclear imaging techniques for cardiac metabolism must be viewed in context with the principles of metabolic regulation

  • Metabolic remodeling precedes functional and structural remodeling in heart failure

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Figure 1: Metabolic remodeling precedes, triggers, and sustains functional and structural remodeling of the heart.
Figure 2: Mechanisms of lipotoxicity in the heart.
Figure 3: PET scan showing perfusion–metabolism mismatch in hibernating heart tissue as an example of preserved cardiometabolic reserve.
Figure 4: Major pathways and regulatory steps of the metabolism of [123I]-β-methyl-iodophenylpentadecanoic acid in the cardiomyocyte.
Figure 5: Single-photon emission CT showing delayed recovery of regional fatty acid metabolism in heart tissue after transient exercise-induced ischemia ('ischemic memory').

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Acknowledgements

We thank Roxy A Tate for editorial assistance. H Taegtmeyer's laboratory is supported by grants from the National Heart, Lung, and Blood Institute of the US Public Health Service.

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Correspondence to Heinrich Taegtmeyer or Vasken Dilsizian.

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Taegtmeyer, H., Dilsizian, V. Imaging myocardial metabolism and ischemic memory. Nat Rev Cardiol 5 (Suppl 2), S42–S48 (2008). https://doi.org/10.1038/ncpcardio1186

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