The mitochondria harvested at the end of perfusion of control hearts and assayed for respiratory activity had a better function after
ischemia and reperfusion following
trimetazidine injection when
glutamate was used as substrate. The protective effect of
trimetazidine was enhanced when the mitochondria were isolated from hypertrophied perfused rat hearts. In fact the
drug improved both the RCI and QO2 parameters with
glutamate or
succinate as substrates and raised the
glutamate-induced QO2 value of mitochondria extracted from the hypertrophied heart perfused in aerobic conditions. In the aerobically perfused heart
trimetazidine did not change either the levels of tissue
malondialdehyde and
lipofuscin, or the rate of mitochondrial O.2 generation while it reduced the O.2 formation and
malondialdehyde content in the hypertrophied heart. After
ischemia and reperfusion, the
drug reproduced these protective effects in the hypertrophied hearts and reduced the level of tissue
malondialdehyde in control hearts. The protective effect of
trimetazidine against MDA formation was dose-dependent, being more evident at a higher dose (10 mumol/l). Preincubation of rat heart mitochondria with 0.1-10 mumol/l
trimetazidine did not affect
NADH oxidase,
NADH dehydrogenase and
NADH-cytochrome c reductase,
succinate oxidase and
cytochrome c oxidase activities. These results indicate that
trimetazidine injected into isolated rat hearts protects against the damage induced on cardiac energetics and oxidative injuries by moderate
ischemia and reperfusion stress, particularly in
monocrotaline-induced
hypertrophy in the rat heart. We suggest that
trimetazidine reduces the formation of oxidative damage by preserving cardiac mitochondrial function.