Circulation, Vol 87, 972-981, Copyright © 1993 by American Heart Association
TL Broderick, HA Quinney, CC Barker and GD Lopaschuk
BACKGROUND. We have previously shown that increasing myocardial carnitine
levels in fatty acid-perfused isolated working rat hearts dramatically
increases glucose oxidation rates. Since high levels of fatty acids depress
reperfusion recovery of ischemic hearts by inhibiting glucose oxidation, we
determined what effect carnitine has on glucose oxidation during
reperfusion of ischemic hearts. METHODS AND RESULTS. Isolated working rat
hearts were perfused with 11 mM [5-3H/ul- 14C]glucose, 1.2 mM palmitate,
and 100 microU/ml insulin and subjected to a 35-minute period of global
ischemia followed by aerobic reperfusion. Rates of glycolysis and glucose
oxidation were determined by measuring tritiated water and 14CO2
production, respectively. Before ischemia, myocardial carnitine content was
first increased by perfusing hearts during a 60-minute baseline aerobic
perfusion with 10 mM L- carnitine. This resulted in a significant increase
in total myocardial carnitine from 4,804 +/- 358 to 9,692 +/- 2,090 nmol/g
dry wt (mean +/- SD). Glycolysis rates in carnitine-treated hearts were not
significantly altered compared with control hearts during the aerobic
perfusion (2,482 +/- 1,173 versus 1,840 +/- 1,365 nmol glucose.g dry wt- 1
x min-1, respectively). In contrast, glucose oxidation rates in
carnitine-treated hearts were significantly increased before ischemia
compared with control hearts (471 +/- 209 versus 158 +/- 75 nmol glucose.g
dry wt-1 x min-1, respectively). During reperfusion of previously ischemic
hearts, glycolytic rates returned to preischemic values in both
carnitine-treated and control hearts. Glucose oxidation rates also
recovered to preischemic values in these hearts and remained significantly
elevated in carnitine-treated hearts compared with control hearts (283 +/-
113 versus 130 +/- 27 nmol glucose.g dry wt-1 x min-1, respectively).
Mechanical recovery in control hearts returned to 44% of preischemic values
(measured as heart rate-peak systolic pressure product), whereas in
carnitine-treated hearts, mechanical recovery returned to 71% of
preischemic values. CONCLUSIONS. These results suggest that the beneficial
effects of carnitine in the ischemic heart can be explained by the actions
of this compound on overcoming fatty acid inhibition of glucose oxidation.
ARTICLES
Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation
Department of Exercise Physiology, University of Alberta, Edmonton, Canada.
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