© 1995 American Heart Association, Inc.
Articles |
Propionyl L-Carnitine Improvement of Hypertrophied Heart Function Is Accompanied by an Increase in Carbohydrate Oxidation
From the Cardiovascular Disease Research Group, Departments of Pharmacology and Pediatrics (B.O.S., G.D.L.), The University of Alberta, Edmonton, Canada, and the Cardiovascular Research Laboratory (M.F.A.), St Paul's Hospital, Vancouver, Canada.
Abstract Propionyl L-carnitine (PLC) is a
naturally occurring derivative of L-carnitine that can
improve hemodynamic function of hypertrophied rat
hearts. The mechanism(s) responsible for the beneficial effects of PLC
is not known, although improvement of myocardial energy
metabolism has been suggested. In this study, we determined
the effect of PLC on carbohydrate and fatty acid metabolism
in hypertrophied rat hearts. Myocardial hypertrophy was
produced by partial occlusion of the suprarenal aorta of juvenile rats.
Over a subsequent 8-week period, a mild hypertrophy
developed, resulting in a 17% increase in heart weight in these
animals compared with the sham-operated control animals. Myocardial
carnitine was decreased in hypertrophied hearts compared with hearts
from sham-operated animals (4155±383 versus 5924±570 nmol · g
dry wt-1, respectively; P
.05).
Perfusion of isolated working hearts for 60 minutes with buffer
containing 1 mmol/L PLC increased carnitine content in hypertrophied
hearts from 4155±383 to 7081±729 nmol · g dry wt-1
(P.05). In the presence of 1.2 mmol/L palmitate, fatty
acid oxidation rates were not decreased in the hypertrophied hearts
compared with control hearts. PLC treatment did not alter rates of
fatty acid oxidation in control hearts but did result in a small
increase in rates in the hypertrophied hearts. The most dramatic
effect of PLC treatment in hypertrophied hearts was an increase in
glucose oxidation rates from 137±25 to 627±110
nmol · min-1 · g dry wt-1
(P.05) and an increase in lactate oxidation rates from
119±17 to 252±47 nmol · min-1 · g dry
wt-1 (P.05). Glycolytic rates, which were
already significantly elevated in hypertrophied hearts compared with
control hearts, were not altered by PLC treatment. Overall ATP
production from exogenous sources was increased by 64% in
PLC-treated hypertrophic hearts and was accompanied by a significant
increase in cardiac work. The main effect of PLC treatment was to
increase the contribution of glucose oxidation to the relative rate of
ATP production from 11.6% to 21.6%. The contribution of
glucose and palmitate oxidation to ATP production was also
determined in aortic-banded animals treated with 60 mg/kg PLC for
an 8-week period. This treatment was also associated with a significant
improvement in mechanical function in hearts isolated from these
animals compared with untreated animals as well as an increase in the
contribution of glucose oxidation to ATP production. Despite
this improvement of cardiac work after chronic PLC treatment, no
increase in palmitate oxidation was observed in hypertrophied hearts.
These findings indicate that the beneficial effects of PLC in
hypertrophied hearts can be accounted for by a stimulation of ATP
production from carbohydrate oxidation rather than from fatty
acid oxidation. The increase in carbohydrate oxidation may be a
consequence of activation of the pyruvate dehydrogenase complex, by
means of a reduction in the ratio of intramitochondrial acetyl coenzyme
A to coenzyme A.
Key Words: propionyl L-carnitine • myocardial hypertrophy • fatty acid oxidation • glycolysis • glucose oxidation
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