The effects of moderate ischemia pretreatment on myocardial
substrate utilization.
Liedtke, A. James, M. D., Britta Renstrom, Ph. D., Timothy A. Hacker,
M. S., Stephen H. Nellis, Ph. D. With The Technical Assistance Of
Daniel K. Paulson, Emanual Scarbrough, Larry F. Whitesell, and
Catherine R. Kidd.
A. James Liedtke, M.D., Cardiology Section, University of Wisconsin
Hospital and Clinics, 600 Highland Avenue, H6/339, Madison, WI 53792
-3248, Phone: (608) 263-1531, FAX: (608) 263-0405
APStracts 2:0021H, 1995.
The purpose of this report was to directly measure the influence of
ischemia pretreatment on intermediary metabolism, specifically
exogenous glucose utilization and fatty acid oxidation, using
myocardial equilibrium-labeling with [U-14C] palmitate and
[5-3H] glucose. Twenty-one intact, working, extracorporeally
perfused pig hearts were prepared and divided into three groups: 7
CONTROL hearts and 14 pretreated hearts exposed to either one cycle
(n=7) or four cycles (n=7) moderate myocardial ischemia with
preserved coronary washout (PRETREAT1 and PRETREAT4, respectively).
One pretreatment cycle consisted of transient (either 10 min for
PRETREAT1 or 5 min for PRETREAT4) reductions in anterior descending
(LAD) coronary flow (-70_% below aerobic levels) followed by aerobic
reperfusion (20 min for PRETREAT1, 5 min between the first 3 cycles
in PRETREAT4, and 20 min after the fourth cycle). All groups then
underwent 40 min of sustained LAD ischemia (-60_% below aerobic
levels) and 40 min aerobic reperfusion. Regional systolic shortening
and myocardial oxygen consumption declined as expected in CONTROL (
-76 and -46_%, respectively), PRETREAT1 (-107 and -45_%,
respectively), and PRETREAT4 hearts (-59 and -42_%, respectively)
during sustained ischemia. Recovery of myocardial oxygen consumption
was near complete in all groups (82% of preischemic values) whereas
mechanical recovery was delayed in PRETREAT1 hearts (p<0.022 from
CONTROL hearts) during reflow. Pretreatment with one cycle transient
ischemia did not significantly prevent accelerated glycolytic flux
during sustained ischemia (nearly ten-fold increase in CONTROL
hearts) but demonstrably attenuated glycolytic flux in PRETREAT4
hearts (-45% from CONTROL hearts, p<0.046). Glucose utilization
rapidly returned to near aerobic values in all three groups during
reperfusion but was appreciably lower (p<0.004 from control values)
in PRETREAT4 hearts. Fatty acid oxidation averaged 12.3 +/- 1.2 _mol
hr-1 g dry wt-1 in all three groups during sustained ischemia and
21.3 +/- 2.0 _mol hr-1 g dry wt-1 during reperfusion (NS among groups
for either perfusion interval). In conclusion, the effects of
pretreatment with transient, moderate ischemia was dependent on cycle
number, and in the four-cycle group resulted in a clear reduction of
glycolysis noted both during sustained ischemia and reperfusion. In
neither pretreated group was there an influence on regional
mechanical function, oxidative metabolism or fatty acid oxidation.
Received 4 October 1994; accepted in final form 17 January 1995.
APS Manuscript Number H923-4.
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.