TY - JOUR
TI - Trimetazidine protects isolated rat hearts against ischemia-reperfusion
injury in an experimental timing-dependent manner
AU - Pantos, C
AU - Bescond-Jacquet, A
AU - Tzeis, S
AU - Paizis, I and
AU - Mourouzis, I
AU - Moraitis, P
AU - Malliopoulou, V
AU - Politi, ED and
AU - Karageorgiou, H
AU - Varonos, D
AU - Cokkinos, DV
JO - Basic Research in Cardiology
PY - 2005
VL - 100
TODO - 2
SP - 154-160
PB - Springer Berlin Heidelberg
SN - 0300-8428, 1435-1803
TODO - 10.1007/s00395-004-0505-4
TODO - trimetazidine; ischemia-reperfusion injury; metabolism; MAPK kinases
TODO - The present study investigated the tolerance of the isolated rat heart
to ischemia - reperfusion after administration of trimetazidine (TMZ) at
different experimental phases, as well as the possible involvement of
p38 MAPK and JNKs in this response. Isolated rat hearts were perfused in
Langendorff mode. Untreated hearts after stabilization ( S) were
subjected to 20 min of zero-flow global ischemia ( I) and 45 min of
reperfusion ( R), ( NORM), n = 9. TMZ (10(-5) M) was administered ( in
the perfusate): a) only at S phase, (TMZ-STAB), n = 8, b) only at R,
(TMZ-REP), n = 8 and c) during both S and R, (TMZ-STAB+ REP), n = 8.
Recovery of left ventricular developed pressure at 45 min of R (Rec) was
significantly higher in TMZ-STAB and TMZ-STAB+ REP and LDH release was
lower in TMZ-STAB+ REP and TMZ-STAB than NORM, [1153.2 (121.0) and
1152.1 (86.8) vs 1573.5 (138.2), P < 0.05]. TMZ induced cardioprotection
did not involve p38 MAPK and JNKs. Phospho-p38 MAPK and JNKs levels
after I/R were not changed with TMZ treatment. In TMZ-REP, Rec and LDH
release were similar to NORM, but the rate of functional recovery (
ratio of Rec at 10 min of R to Rec) was 86.7% (13.3) for TMZ-REP vs
53.8% (7.7) for NORM, P < 0.05. This effect was associated with
decreased myocardial lactate content early at reperfusion. In
conclusion, preischemic administration of TMZ protects against I/R
injury while TMZ given only at reperfusion accelerates recovery of
function without reducing the extent of injury.
ER -