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. 1993 Sep;110(1):275–280. doi: 10.1111/j.1476-5381.1993.tb13805.x

Dissociation of the anti-ischaemic effects of cloricromene from its anti-platelet activity.

P S Lidbury 1, R Cirillo 1, J R Vane 1
PMCID: PMC2176012  PMID: 8220889

Abstract

1. Cloricromene is a non-anticoagulant coumarin derivative with anti-platelet and anti-leukocyte properties, which has beneficial effects in various models of ischaemia and shock. 2. We have assessed the effects of cloricromene on (a) ex vivo platelet aggregation, and (b) infarct size using a model of myocardial ischaemia in the anaesthetized rabbit. 3. Cloricromene (1-1000 micrograms kg-1 min-1 for 15 min) induced a dose-dependent inhibition of ex vivo platelet aggregation, causing only a minimal increase in heart rate and no change in mean arterial blood pressure. The inhibitory activity was considerably stronger when platelet aggregation was induced by collagen than by ADP. 4. Cloricromene inhibited ex vivo platelet aggregation in rabbits pretreated with indomethacin (5 mg kg-1) and this inhibition persisted for 30-60 min. 5. The model of myocardial ischaemia involved 1 h occlusion of the first antero-lateral branch of the left coronary artery followed by 2 h of reperfusion. Infusion of cloricromene (30 or 300 micrograms kg-1 min-1), ibuprofen (80 micrograms kg-1 min-1) or vehicle began 15 min prior to occlusion, and continued throughout the experiment. 6. While area at risk was similar for all groups studied, cloricromene (30 or 300 micrograms kg-1 min-1) or ibuprofen caused a reduction in infarct size, and decreased myeloperoxidase activity in the tissue of the infarcted myocardium. 7. Cloricromene at 300 micrograms kg-1 min-1 also reduced the occlusion-induced elevation of the ST-segment of the rabbit electrocardiogram, and inhibited platelet aggregation ex vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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