Cardiac responses to induced lactate oxidation: nmr analysis of
metabolic equilibria.
Lewandowski, E. Douglas, Lisa A. Damico, Lawrence T. White, and Xin
Yu.
NMR Center, Department of Radiology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA
APStracts 2:0048H, 1995.
The role of lactate, as a source of pyruvate oxidation in supporting
cardiac work, energetics, and formation of oxidative metabolites, was
examined in normal myocardium. 13C and 31P NMR spectra were acquired
from isolated rabbit hearts supplied 2.5 mM [3-13C] lactate or
[3-13C] pyruvate with or without stimulation of pyruvate
dehydrogenase (PDH) by dichloroacetate (DCA). Similar workloads
determined by rate pressure products were noted with pyruvate
(21700+2400; Mean+SE) and lactate (18970+1510). Oxygen consumption
was similar in all four groups with means between 19.0 - 22.2
[mu]mol/min/g dry weight (SE= 1.6-2.0) as was the ratio of
phosphocreatine to ATP with means between 1.8 - 2.1 (SE = 0.1 - 0.6).
Intracellular pH, determined from 31P NMR spectra, was essentially
the same with pyruvate (7.06 +/- 0.02) and lactate (7.05 +/- 0.04). 13C
enrichment of glutamate was higher with lactate (92%) than pyruvate
(70%). Pyruvate plus DCA induced no change in glutamate content at 9
-10 [mu]mol/g, but 13C-enrichment increased to 83%, while lactate plus
DCA maintained enrichment at 90%. Levels of [alpha]-ketoglutarate were
lower with lactate (1.81 [mu]mol/g) than with pyruvate (2.36 [mu]mol/g).
Lactate plus DCA elevated glutamate by 60% with a proportional
increase in [alpha]-ketoglutarate. Thus, the balance between glutamate and
[alpha]-ketoglutarate was affected by substrate supply only and not by PDH
activation. The results suggest that the equilibrium between [alpha]
-ketoglutarate and glutamate is sensitive to cytosolic redox state, an
important consideration for 13C NMR analyses that rely on glutamate.
In conclusion, lactate and pyruvate are able to support similar
function and energetics through differences in the balance of
oxidative, intermediary metabolites.
Received 17 October 1994; accepted in final form 31 January 1995.
APS Manuscript Number H932-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.