The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-α production in myocardial ischaemia-reperfusion injury

Abstract

The effects of cloricromene, a coumarine derivative, were studied in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 68 ± 4 %; necrotic area/total area = 48 ± 3 %) high serum creatinphosphokinase activity (Sham MI/R = 29 ± 8 U/ml; MI/R = 205 ± 11 U/ml) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation), in the area-at-risk (6.3 ± 0.5 U × 10 −3/g tissue). necrotic area (6.5 ± 0.5 U × 10 −3/g tissue). Furthermore, serum TNF-α was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-α was also enhanced. The administration of cloricromene (2 mg/kg, 5 minutes after the onset of reperfusion) significantly reduced myocardial injury (necrotic area/area-at-risk 30 ± 1.3 %; necrotic area/total area = 25 ± 1.5) blunted the increase in serum creatinphosphokinase activity (92 ± 5 U/ml) and lowered myeloperoxidase activity in area-at-risk (2.5 ± 0.2 U × 10 −3/g tissue) and in necrotic area (2.2 ± 0.3 U × 10 −3/g tissue) and decreased the serum and macrophage levels of TNF-α.