This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 119/13/1736    most recent CIRCULATIONAHA.108.816116v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Turer, A. T. Articles by Podgoreanu, M. V. Search for Related Content PubMed PubMed Citation Articles by Turer, A. T. Articles by Podgoreanu, M. V. Related Collections Biochemistry and metabolism Energy metabolism Genomics CV surgery: other Related Article

(Circulation. 2009;119:1736-1746.)
© 2009 American Heart Association, Inc.

Genetics

Metabolomic Profiling Reveals Distinct Patterns of Myocardial Substrate Use in Humans With Coronary Artery Disease or Left Ventricular Dysfunction During Surgical Ischemia/Reperfusion

Aslan T. Turer, MD; Robert D. Stevens, PhD; James R. Bain, PhD; Michael J. Muehlbauer, PhD; Johannes van der Westhuizen, MD; Joseph P. Mathew, MD; Debra A. Schwinn, MD; Donald D. Glower, MD; Christopher B. Newgard, PhD^*; Mihai V. Podgoreanu, MD^*

From the Division of Cardiovascular Medicine (A.T.T.), Division of Cardiothoracic Anesthesia and Critical Care, Duke Perioperative Genomics Program (J.v.d.W., J.P.M., M.V.P.), Division of Cardiothoracic Surgery (D.D.G.), Sarah W. Stedman Nutrition and Metabolism Center (R.D.S., J.R.B., M.J.M., C.B.N.), and Departments of Pharmacology and Cancer Biology (C.B.N.), Duke University Medical Center, Durham, NC, and Departments of Anesthesiology, Pharmacology, and Genome Sciences, University of Washington, Seattle (D.A.S.).

Correspondence to Dr Aslan T. Turer, MD, Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 31297, Erwin Rd, Durham, NC 27710. E-mail turer001{at}mc.duke.edu

Received August 25, 2008; accepted January 9, 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.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 119: 1691-1693. [Extract] [Full Text]

This article has been cited by other articles:

				E. Mervaala, A. Biala, S. Merasto, J. Lempiainen, I. Mattila, E. Martonen, O. Eriksson, M. Louhelainen, P. Finckenberg, P. Kaheinen, et al. Metabolomics in Angiotensin II-Induced Cardiac Hypertrophy Hypertension, February 1, 2010; 55(2): 508 - 515. [Abstract] [Full Text] [PDF]

				G. D. Lopaschuk, J. R. Ussher, C. D. L. Folmes, J. S. Jaswal, and W. C. Stanley Myocardial Fatty Acid Metabolism in Health and Disease Physiol Rev, January 1, 2010; 90(1): 207 - 258. [Abstract] [Full Text] [PDF]

				J. R. Bain, R. D. Stevens, B. R. Wenner, O. Ilkayeva, D. M. Muoio, and C. B. Newgard Metabolomics Applied to Diabetes Research: Moving From Information to Knowledge Diabetes, November 1, 2009; 58(11): 2429 - 2443. [Full Text] [PDF]

				H. Ashrafian and S. Neubauer Metabolomic Profiling of Cardiac Substrate Utilization: Fanning the Flames of Systems Biology? Circulation, April 7, 2009; 119(13): 1700 - 1702. [Full Text] [PDF]