The metabolic fate of glucose in reversible low-flow ischemia of
the isolated working rat heart.
Bolukoglu, Hakki, Gary W. Goodwin, Patrick H. Guthrie, Sonya G.
Carmical, T. Minsue Chen, and Heinrich Taegtmeyer.
University of Texas Houston Medical School, Department of Internal
Medicine, Division of Cardiology, Houston,TX 77030
APStracts 2:0382H, 1995.
The acute adaptation of myocardial glucose metabolism in response to
low-flow ischemia and reperfusion was investigated in isolated
working rat hearts perfused with bicarbonate saline containing
glucose (10 mM), and insulin (40U/ml). Tritiated glucose (0.05
Ci/ml), labeled in the 2, 5 or 6 positions was used to assess rates
of glucose transport and phosphorylation, flux from glucose to
pyruvate, and oxidation of exogenous glucose, respectively. Rates of
glycogen synthesis and glycolysis were also assessed. Low-flow
ischemia was induced by reducing coronary perfusion pressure from 100
cmH2O to 35 cmH2O for 30 min. Preload was kept constant at 15 cmH2O
throughout the experiments. During low-flow ischemia coronary flow
and cardiac power decreased by more than two-thirds, while rates of
glucose uptake, and flux from glucose to pyruvate remained unchanged.
Glucose oxidation declined by 61% and rates of lactate release more
than doubled. Under aerobic conditions 57% of exogenous glucose was
oxidized, 29% was converted to lactate, and 14% was incorporated into
glycogen. During ischemia 29% of glucose was oxidized, and 57% was
converted to lactate. The fractional enrichment of glycogen remained
the same. During reperfusion, glucose oxidation returned to the
preischemic rates, while 24% of glucose was converted to lactate and
19% appeared in glycogen. With isoproterenol added during ischemia,
glucose uptake increased by 41%, glycogen fell by 44%, and lactate
release increased four-fold. No effect was seen with pacing. We
conclude that with short-term, low-flow reversible ischemia and
glucose as the only exogenous substrate, net glucose uptake remains
unchanged, while there is a reversible redirection between glycolysis
and glucose oxidation. Glycogen synthesis continues during ischemia
and is enhanced during reperfusion.
Received 29 March 1995; accepted in final form 11 August 1995.
APS Manuscript Number H302-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.