Lm. King et al., Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-flow ischemia, AM J P-HEAR, 280(3), 2001, pp. H1173-H1181
Citations number
38
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
To determine whether the effects of fatty acids on the diabetic heart durin
g ischemia involve altered glycolytic ATP and proton production, we measure
d energetics and intracellular pH (pH(i)) by using P-31 NMR spectroscopy pl
us [2-H-3] glucose uptake in isolated rat hearts. Hearts from 7-wk streptoz
otocin diabetic and control rats, perfused with buffer containing 11 mM glu
cose, with or without 1.2 mM palmitate or the ketone bodies, 4 mM beta -hyd
roxybutyrate plus 1 mM acetoacetate, were subjected to 32 min of low-flow (
0.3 ml . g wet wt(-1).min(-1)) ischemia, followed by 32 min of reperfusion.
In control rat hearts, neither palmitate nor ketone bodies altered the rec
overy of contractile function. Diabetic rat hearts perfused with glucose al
one or with ketone bodies, had functional recoveries 50% lower than those o
f the control hearts, but palmitate restored recovery to control levels. In
a parallel group with the functional recoveries, palmitate prevented the 5
4% faster loss of ATP in the diabetic, glucose-perfused rat hearts during i
schemia, but had no effect on the rate of ATP depletion in control hearts.
Palmitate decreased total glucose uptake in control rat hearts during low-f
low ischemia, from 106 +/- 17 to 52 +/- 12 mu mol/g wet wt, but did not alt
er the total glucose uptake in the diabetic rat hearts, which was 42 +/- 5
mu mol/g wet wt. Recovery of contractile function was unrelated to pHi duri
ng ischemia; the glucose-perfused control and palmitate-perfused diabetic h
earts had end-ischemic pH(i) values that were significantly different at 6.
36 +/- 0.04 and 6.60 +/- 0.02, respectively, but had similar functional rec
overies, whereas the glucose-perfused diabetic hearts had significantly low
er functional recoveries, but their pHi was 6.49 +/- 0.04. We conclude that
fatty acids, but not ketone bodies, protect the diabetic heart by decreasi
ng ATP depletion, with neither having detrimental effects on the normal rat
heart during low-flow ischemia.