CLORICROMENE REDUCES INFARCT SIZE AND ALTERS POSTISCHEMIC BLOOD-FLOW DEFECTS IN DOG MYOCARDIUM

1. The aim of the present investigation was to evaluate the effect of cloricromene on myocardial infarct size, regional myocardial blood flo w and neutrophil accumulation in a canine model of ischaemia-reperfusi on. 2. Dogs were instrumented to measure blood pressure, left anterior descending (LAD) coronary flow (flow probe) and regional myocardial b lood flow (coloured microspheres), Two groups were studied: (i) CLO (n = 8) received an infusion of cloricromene (15 mu g/kg per min); and ( ii) VEH (It = 8) received saline. Infusions began at the onset of isch aemia (60 min) and continued through reperfusion (180 min). 3. Haemody namic responses were not different between groups. CIoricromene reduce d the area of necrosis expressed as a percentage of the area at risk f rom 35 +/- 3% in the VEH group to 23 +/- 4% in the CLO group (P<0.05), Regional myocardial blood how in the ischaemic region was different b etween groups; VEH dogs showed an early reperfusion hyperaemia followe d by a progressive reduction in how while CLO dogs exhibited a gradual increase in reflow in the absence of an early hyperaemic response (P< 0.05). Left anterior descending how was enhanced during the reperfusio n period in the CLO group compared with VEH (P<0.05), Cloricromene red uced polymorphonuclear neutrophil (PMN) infiltration (myeloperoxidase activity) in all myocardial regions when compared with VEH (non-ischae mic zone, 0.34 +/- 0.54 vs 0.05 +/- 0.01 IU/100 mg; ischaemic zone, 2. 03 +/- 0.80 vs 0.24 +/- 0.08 IU/100 mg; and necrotic zone, 0.56 +/- 0. 04 vs 3.59 +/- 1,09 IU/100 mg for VEH vs CLO groups, respectively; P<0 ,01), In a separate in vitro preparation, cloricromene reduced adheren ce of platelet-activating factor (PAF)-stimulated PMN to canine corona ry endothelium. Stimulation of PMN by 100 nmol/L PAF resulted in adher ence of 176 +/- 36 compared with 48 +/- 12 cells/mm(2) in PAF-stimulat ed PMN treated with 100 mu mol cloricromene (P<0.001). 4. These data i ndicate that cloricromene reduces myocardial infarct size in a canine model of ischaemia-reperfusion injury. Postischaemic blood how pattern s are significantly different in cloricromene-treated dogs. Cloricrome ne-mediated reductions in infarct size, neutrophil accumulation and ad herence may play a role in this effect.