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


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.
Turer
Aslan T
AT
Division of Cardiology, Department of Medicine, Duke University Medical Center, Box 31297, Erwin Rd, Durham, NC 27710, USA. turer001@mc.duke.edu
Stevens
Robert D
RD
Bain
James R
JR
Muehlbauer
Michael J
MJ
van der Westhuizen
Johannes
J
Mathew
Joseph P
JP
Schwinn
Debra A
DA
Glower
Donald D
DD
Newgard
Christopher B
CB
Podgoreanu
Mihai V
MV
D000368:Aged; D015308:Anaerobic Threshold / Q000502:physiology; D002302:Cardiac Output; D002315:Cardiopulmonary Bypass; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D003324:Coronary Artery Disease / Q000378:metabolism / Q000601:surgery; D005260:Female; D006321:Heart / Q000502:physiology; D006324:Heart Arrest, Induced; D006331:Heart Diseases / Q000378:metabolism* / Q000601:surgery*; D006801:Humans; D007431:Intraoperative Complications / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000502:physiology*; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000601:surgery; D009206:Myocardium / Q000378:metabolism; D011183:Postoperative Complications / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000601:surgery
C116917:acylcarnitine; D019344:Lactic Acid; D002331:Carnitine