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The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-alpha production in myocardial ischaemia-reperfusion injury.
- Source :
-
Life sciences [Life Sci] 1993; Vol. 53 (4), pp. 341-55. - Publication Year :
- 1993
-
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 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (6.5 +/- 0.5 U x 10(-3)/g tissue). Furthermore, serum TNF-alpha was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-alpha 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 x 10(-3)/g tissue) and in necrotic area (2.2 +/- 0.3 U x 10(-3)/g tissue) and decreased the serum and macrophage levels of TNF-alpha. These data indicate that cloricromene exerts beneficial effects on myocardial ischaemia/reperfusion injury. Finally, since we measured increased serum levels of TNF-alpha that were blunted by the cloricromene treatment, our data are consistent with an involvement of TNF-alpha in the reperfusion injury induced by myocardial ischaemia.
- Subjects :
- Analysis of Variance
Animals
Chromonar pharmacology
Chromonar therapeutic use
Creatine Kinase blood
Male
Myocardial Reperfusion Injury blood
Myocardial Reperfusion Injury enzymology
Myocardial Reperfusion Injury pathology
Necrosis prevention & control
Peroxidase blood
Rats
Rats, Sprague-Dawley
Survival Analysis
Chromonar analogs & derivatives
Leukocytes drug effects
Myocardial Reperfusion Injury prevention & control
Tumor Necrosis Factor-alpha drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 53
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 8392130
- Full Text :
- https://doi.org/10.1016/0024-3205(93)90753-p