Myocardial glycogen depletion contributes to the protective effects
of ischemic preconditioning in the rat heart in vivo.
McNulty, Patrick H., Alisa Darling, Jennifer M. Whiting.
Section of Cardiovascular Medicine, VA Connecticut Medical Center
and Yale University School of Medicine, New Haven CT 06520
APStracts 3:0269H, 1996.
Ischemic preconditioning depletes the myocardium of glycogen, thus
blunting lactic acidosis during subsequent episodes of ischemia.
Preconditioning also protects against reperfusion arrhythmias and
infarction. To test whether glycogen depletion is necessary for this
ischemic tolerance, we preconditioned two groups of intact rats with
a series of 3-minute coronary artery occlusions. In one group,
preconditioning lowered the glycogen concentration of the ischemic
region by 50% (24.9 + 2.5 to 12.5 + 1.8 [mu]mol/g, p<0.01). In
the other, the heart was first loaded with glycogen via glucose
-insulin infusion, so that preconditioning merely reduced its glycogen
concentration back to normal physiologic levels. Compared to non
-preconditioned controls, preconditioned rats with both normal and
subnormal glycogen concentrations were protected from reperfusion
arrhythmias following a 6-minute coronary occlusion (incidence:
controls = 100%; normal glycogen = 11%; reduced glycogen = 11%). In
contrast, only rats with subnormal glycogen concentration after
preconditioning exhibited reduced lactate formation and infarct size
following a 45-minute coronary occlusion (infarct size (% of risk
area): controls = 53 + 10% ; normal glycogen = 50 + 16%, p = NS;
subnormal glycogen = 18 + 10%, p<0.01). Thus in the intact rat,
myocardial glycogen depletion appears to be necessary for the infarct
limiting, but not the anti-arrhythmic, effects of ischemic
preconditioning.
Received 3 October 1995; accepted in final form 7 May 1996.
APS Manuscript Number H931-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96