Fm. Williams et al., TRIMETAZIDINE INHIBITS NEUTROPHIL ACCUMULATION AFTER MYOCARDIAL-ISCHEMIA AND REPERFUSION IN RABBITS, Journal of cardiovascular pharmacology, 22(6), 1993, pp. 828-833
Interventions that inhibit neutrophil infiltration into myocardial tis
sue after ischaemia and reperfusion are reported to reduce the size of
the infarct. We examined whether administration of trimetazidine, whi
ch is reported to reduce myocardial infarct size, affects this process
. [In-111]Neutrophils and [I-125]albumin were administered intravenous
ly (i.v.) to anaesthetized rabbits to allow measurement of cell accumu
lation and changes in microvascular plasma protein leakage. A 30-min p
eriod of coronary artery occlusion followed by 3-h reperfusion was use
d, and the area at risk (AR) myocardium was defined by dye exclusion.
Twelve rabbits received 2.5 mg/kg trimetazidine i.v., 10 min before co
ronary artery occlusion; the 13 controls received saline. In the contr
ol group, the number of [In-111]neutrophils/g tissue in the AR (30,591
+/- 6,725) was significantly greater than in the normal zone (NZ, 11,
519 +/- 1,605, p < 0.01). In the trimetazidine-treated group, the numb
er of [In-111]neutrophils in the AR was significantly lower than in th
e control group (12,717 +/- 1,958 [In-111]neutrophils/g, p < 0.01). Th
ere was no significant difference in neutrophil content of the NZ (7,8
32 +/- 1,117 [In-111]neutrophils/g) in treated animals as compared wit
h that in control. Accumulation of [In-111]neutrophils in response to
intradermal administration of leukotriene B4, interleukin-8 (IL-8), or
zymosan-activated plasma was not affected by the drug. The effect of
trimetazidine on neutrophil accumulation into postischemic reperfused
myocardium therefore does not appear to result from a direct action on
the neutrophil.