AJP - Cell Physiology, Vol 263, Issue 1 C17-C23, Copyright © 1992 by American Physiological Society
Metabolic substrates can alter postischemic recovery in preconditioned ischemic heart
T. A. Fralix, C. Steenbergen, R. E. London and E. Murphy
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park 27709.
The mechanisms that contribute to myocardial cell injury are not well
understood. Furthermore, the ability of reperfusion conditions to modify
ischemic injury is unclear. Recent studies have indicated that glucose
utilization may improve ionic homeostasis. Because considerable derangement
of ion concentrations occurs during ischemia, glucose utilization may be
beneficial when stimulated during the reperfusion period. The effects of
glycolytic vs. mitochondrial substrates on postischemic contractile
function, high-energy phosphates and ion balance (intracellular Ca2+ and
pH) were determined. Reperfusion conditions were compared in the
"preconditioned ischemic" heart where baseline contractile recovery during
reperfusion with glucose as the sole exogenous substrate was 74 +/- 5% (n =
10). Contractile recovery was determined for reperfusion with pyruvate (14
+/- 2%, n = 10), pyruvate+glucose (23 +/- 4%, n = 10), deoxyglucose+acetate
(25 +/- 4%, n = 10), and lactate+glucose (60 +/- 11%, n = 10). Contractile
dysfunction could not be attributed to differences in high-energy phosphate
contents. Elevated levels of intracellular Ca2+ during reperfusion were,
however, correlated with poor contractile function. After 20 min of
reperfusion, the mean time-averaged intracellular Ca2+ values, measured
with 19F-nuclear magnetic resonance of
5-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded
hearts, were 994 +/- 110 nM (glucose, n = 5), 2,270 +/- 494 nM (pyruvate, n
= 5), 2,671 +/- 419 nM (pyruvate+glucose, n = 5), 2,382 +/- 480 nM
(deoxyglucose+acetate, n = 5), and 1,019 +/- 33 nM (lactate+glucose, n =
5). These results are consistent with a beneficial role for glucose
utilization during reperfusion, where enhanced recovery of contractile
function and ionic homeostasis were observed.
