Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits.
Interventions that inhibit neutrophil infiltration into myocardial tissue after ischaemia and reperfusion are reported to reduce the size of the infarct. We examined whether administration of trimetazidine, which is reported to reduce myocardial infarct size, affects this process. [111In]Neutrophils and [125I]albumin were administered intravenously (i.v.) to anaesthetized rabbits to allow measurement of cell accumulation and changes in microvascular plasma protein leakage. A 30-min period of coronary artery occlusion followed by 3-h reperfusion was used, 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 coronary artery occlusion; the 13 controls received saline. In the control group, the number of [111In]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 number of [111In]neutrophils in the AR was significantly lower than in the control group (12,717 +/- 1,958 [111In]neutrophils/g, p < 0.01). There was no significant difference in neutrophil content of the NZ (7,832 +/- 1,117 [111In]neutrophils/g) in treated animals as compared with that in control. Accumulation of [111In]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 post-ischaemic reperfused myocardium therefore does not appear to result from a direct action on the neutrophil.
Williams
F M
FM
Department of Applied Pharmacology, National Heart & Lung Institute, London, England.
Tanda
K
K
Kus
M
M
Williams
T J
TJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects*; D011817:Rabbits; D014292:Trimetazidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015054:Zymosan / Q000008:administration & dosage / Q000494:pharmacology
D016209:Interleukin-8; D007975:Leukotriene B4; D015054:Zymosan; D014292:Trimetazidine