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Circulation. 2002 Jan 22;105(3):367-72.

Mitochondrial preference for short chain fatty acid oxidation during coronary artery constriction.

Author information

1
Program in Integrative Cardiac Metabolism, Department of Physiology, University of Illinois at Chicago, USA. dougl@uic.edu

Abstract

BACKGROUND:

Reduced fatty acid oxidation in hypoperfused myocardium is believed to result from impaired oxidation in mitochondria. This study suggests another mechanism, that oxidative capacity exceeds regulated entry of long chain fatty acid (LCFA). The ability of myocardium to oxidize fatty acids and metabolize glucose during stenosis was examined in open chest, anesthetized pigs.

METHODS AND RESULTS:

The left anterior descending (LAD) coronary artery was infused for 40 minutes (5 mL/min LAD) with [2-(13)C] butyrate (4 mmol/L), a short chain fatty acid (SCFA), plus [2-(13)C] glucose (10 mmol/L) in either nonischemic controls (n=4) or at the end of 5 hours of LAD flow reduction (40%, n=7). With LAD constriction, left ventricular wall thickening fell 45+/-8% (P<0.01). Despite glycolytic production of lactate and alanine, hypoperfused myocardium preferentially oxidized SCFA over endogenous LCFA. SCFA accounted for 63+/-4% (mean+/-SEM) of carbon units entering oxidation in both ischemic epicardium and endocardium versus only 38+/-4% and 40+/-6% in respective samples from normal myocardium (P<0.002). Unexpectedly, SCFA contributions were elevated in both endocardium and epicardium despite preserved epicardial blood flow versus a 58+/-9% drop in endocardial flow (P<0.05). No significant oxidation of glucose was evident, indicating that unlabeled fuels were primarily LCFA.

CONCLUSIONS:

Because SCFA bypass LCFA transport into mitochondria, during LAD constriction, mitochondrial capacity to oxidize fatty acid exceeds LCFA entry for oxidation. Importantly, metabolic changes were disassociated from transmural tissue perfusion. These findings suggest that signals other than oxygen availability regulate fatty acid use during hypoperfusion.

PMID:
11804994
[Indexed for MEDLINE]

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