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Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion.

Publication ,  Journal Article
Turer, AT; Stevens, RD; Bain, JR; Muehlbauer, MJ; van der Westhuizen, J; Mathew, JP; Schwinn, DA; Glower, DD; Newgard, CB; Podgoreanu, MV
Published in: Circulation
April 7, 2009

BACKGROUND: Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of preexisting ventricular state on ischemia-induced metabolic derangements has not been established. METHODS AND RESULTS: We applied a mass spectrometry-based platform to profile 63 intermediary metabolites in serial paired peripheral arterial and coronary sinus blood effluents obtained from 37 patients undergoing cardiac surgery, stratified by presence of coronary artery disease and left ventricular dysfunction. The myocardium was a net user of a number of fuel substrates before ischemia, with significant differences between patients with and without coronary artery disease. After reperfusion, significantly lower extraction ratios of most substrates were found, as well as significant release of 2 specific acylcarnitine species, acetylcarnitine and 3-hydroxybutyryl-carnitine. These changes were especially evident in patients with impaired ventricular function, who exhibited profound limitations in extraction of all forms of metabolic fuels. Principal component analysis highlighted several metabolic groupings as potentially important in the postoperative clinical course. CONCLUSIONS: The preexisting ventricular state is associated with significant differences in myocardial fuel uptake at baseline and after ischemia/reperfusion. The dysfunctional ventricle is characterized by global suppression of metabolic fuel uptake and limited myocardial metabolic reserve and flexibility after global ischemia/reperfusion stress in the setting of cardiac surgery. Altered metabolic profiles after ischemia/reperfusion are associated with postoperative hemodynamic course and suggest a role for perioperative metabolic monitoring and targeted optimization in cardiac surgical patients.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

April 7, 2009

Volume

119

Issue

13

Start / End Page

1736 / 1746

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Postoperative Complications
  • Myocardium
  • Myocardial Reperfusion Injury
  • Middle Aged
  • Metabolome
  • Male
  • Lactic Acid
  • Intraoperative Complications
  • Humans
 

Citation

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Turer, A. T., Stevens, R. D., Bain, J. R., Muehlbauer, M. J., van der Westhuizen, J., Mathew, J. P., … Podgoreanu, M. V. (2009). Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion. Circulation, 119(13), 1736–1746. https://doi.org/10.1161/CIRCULATIONAHA.108.816116
Turer, Aslan T., Robert D. Stevens, James R. Bain, Michael J. Muehlbauer, Johannes van der Westhuizen, Joseph P. Mathew, Debra A. Schwinn, Donald D. Glower, Christopher B. Newgard, and Mihai V. Podgoreanu. “Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion.Circulation 119, no. 13 (April 7, 2009): 1736–46. https://doi.org/10.1161/CIRCULATIONAHA.108.816116.
Turer AT, Stevens RD, Bain JR, Muehlbauer MJ, van der Westhuizen J, Mathew JP, et al. Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion. Circulation. 2009 Apr 7;119(13):1736–46.
Turer, Aslan T., et al. “Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion.Circulation, vol. 119, no. 13, Apr. 2009, pp. 1736–46. Pubmed, doi:10.1161/CIRCULATIONAHA.108.816116.
Turer AT, Stevens RD, Bain JR, Muehlbauer MJ, van der Westhuizen J, Mathew JP, Schwinn DA, Glower DD, Newgard CB, Podgoreanu MV. Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion. Circulation. 2009 Apr 7;119(13):1736–1746.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

April 7, 2009

Volume

119

Issue

13

Start / End Page

1736 / 1746

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Postoperative Complications
  • Myocardium
  • Myocardial Reperfusion Injury
  • Middle Aged
  • Metabolome
  • Male
  • Lactic Acid
  • Intraoperative Complications
  • Humans