TY - JOUR
T1 - Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart
AU - Barak, Chen
AU - Reed, Mark K.
AU - Maniscalco, Stephen P.
AU - Sherry, Dean
AU - Malloy, Craig R
AU - Jessen, Michael E
PY - 1998/3
Y1 - 1998/3
N2 - The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen- consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 ± 0.28 to 5.81 ± 1.16 μmol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 ± 0.42 μmol/min/g dry weight) compared with untreated ischemic hearts (0.87 ± 0.28 μmol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.
AB - The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen- consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 ± 0.28 to 5.81 ± 1.16 μmol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 ± 0.42 μmol/min/g dry weight) compared with untreated ischemic hearts (0.87 ± 0.28 μmol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.
KW - C Nuclear magnetic resonance
KW - Dichloroacetate
KW - Ischemia
KW - Myocardial metabolism
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U2 - 10.1097/00005344-199803000-00002
DO - 10.1097/00005344-199803000-00002
M3 - Article
C2 - 9514176
AN - SCOPUS:0031916203
SN - 0160-2446
VL - 31
SP - 336
EP - 344
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -