© 1997 American Heart Association, Inc.
Articles |
Altered Metabolite Exchange Between Subcellular Compartments in Intact Postischemic Rabbit Hearts
From the NMR Center (E.D.L., X.Y., L.T.W., J.M.O.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass, and the Department of Physiology (K.F.L., C.D.), Hershey Medical Center, Pennsylvania State University, Hershey.
Correspondence to E. Douglas Lewandowski, PhD, NMR Center, Massachusetts General Hospital, Building 149, 13th St, Charlestown, MA 02129. E-mail doug{at}nmr.mgh.harvard.edu
Abstract To examine metabolic regulation in
postischemic hearts, we examined oxidative recycling of
13C within the glutamate pool (GLU) of intact rabbit
hearts. Isolated hearts oxidized 2.5 mmol/L
[2-13C]acetate during normal conditions (n=6) or during
reperfusion after 10 minutes of ischemia (n=5).
13C-Nuclear magnetic resonance spectra were acquired every
1 minute. Kinetic analysis of 13C incorporation
into GLU provided both tricarboxylic acid (TCA) cycle flux and the
interconversion rate (F1) between the TCA cycle
intermediate, 
-ketoglutarate (-KG), and the largely cytosolic
GLU. The rate-pressure product in postischemic hearts
was 46% of normal (P<.05). No difference in substrate
utilization occurred between groups, with acetate accounting for 92%
of the carbon units entering the TCA cycle at the citrate synthase
step. TCA cycle flux in postischemic hearts was normal
(normal hearts, 10.7
µmol·min-1·g-1;
postischemic hearts, 9.4
µmol·min-1·g-1),
whereas F1 was 72% lower at 2.9±0.4 versus 10.2±2.5
µmol·min-1·g-1
(mean±SE) in normal hearts (P<.05). From additional hearts
perfused with 2.5 mmol/L [2-13C]acetate plus
supplemental 5 mmol/L glucose, any potential differences in
endogenous carbohydrate availability were proved not to
account for the reduced rate -KG and GLU exchange, which remained
depressed in postischemic hearts. However, specific
activities of the transaminase enzyme, catalyzing chemical exchange of
-KG and GLU, were the same, and transaminase flux was 100
µmol·min-1·g-1
in postischemic hearts versus 68
µmol·min-1·g-1
in normal hearts. Normal transaminase activity and the increased flux
in postischemic hearts are contrary to the reduced
F1. The findings indicate reduced metabolite transport
rates across the mitochondrial membranes of stunned
myocardium, particularly through the reversible
-KG–malate carrier.
Key Words: stunned myocardium • tricarboxylic acid cycle • mitochondria • reperfusion • nuclear magnetic resonance spectroscopy
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