AJP - Regulatory, Integrative and Comparative Physiology, Vol 242, Issue 5 533-R544, Copyright © 1982 by American Physiological Society
Computer simulation of energy metabolism in acidotic cardiac ischemia
M. J. Achs and D. Garfinkel
Construction and fit to experimental data of a computer model of
glycolysis, the tricarboxylic acid cycle, and related metabolism in the
perfused rat heart involving 63 enzyme submodels is described. The
experimental preparation simulated is a rat heart perfused with Krebs
bicarbonate solution containing glucose and insulin whose pH was lowered to
6.6 by equilibration with 35% CO2-65% O2. The glycolytic rate falls sharply
and ischemia results, becoming apparent after 3.5 min. The model initially
ascribes the fall in glycolysis largely to inhibition of hexokinase by
accumulated glucose 6-phosphate and inactivation of phosphofructokinase by
the low pH and subsequently to cytoplasmic glucose depletion owing to
limitation of glucose uptake by the external acidosis. At the same time
there is insufficiently deep hypoxia to trigger substantial mobilization of
endogenous fuels (e.g., glycogenolysis or fatty acid mobilization, so that
these hearts become ischemic primarily owing to a shortage of metabolic
fuel.
