Contribution of leukocyte infiltration to lipoperoxidation occurring in the non-ischemic region of the rat heart submitted to permanent left coronary artery occlusion.
Previous studies have shown that during regional myocardial ischemia, the non-ischemic zone may be submitted to metabolic and structural alterations. In the present study, we have examined whether an inflammatory process could be responsible for increased lipoperoxidation in the non-ischemic zone of the rat heart subjected to permanent coronary artery ligation. Forty-eight hours after coronary artery ligation, tissue levels of malondialdehyde (MDA), taken as an index of lipoperoxidation, measured in the non-ischemic zone was increased by 25% when compared to sham operated hearts. Furthermore, an infiltration of polymorphonuclears was observed by immunofluorescence in the non-ischemic zone, while the activity of the neutrophil-specific myeloperoxidase enzyme (MPO) was significantly increased in that same zone (ligated 1.26 +/- 0.17 U/100 mg wet wt. v sham 0.33 +/- 0.01 U/100 mg wet wt.; P < 0.01). Examination of the temporal changes in MDA content and of MPO activity showed a significant linear decrease in both parameters of 6 to 48 h post-ligation. When compared to placebo, treatment with indomethacin (1 mg/kg, 5 min prior to ligation, then at 12 h intervals up to the harvesting of the hearts) led to a significant reduction in MDA content measured 6, 24 or 48 h after ligation. The treatment had no effect on infarct size measured 48 h after ligation. These results suggest that in the rat heart, permanent regional ischemia is associated with the rapid development of an inflammatory process in the non-ischemic zone which could in part account for the accumulation of lipoperoxidation products in that region.
Physiopathologie Cellulaire Cardiaque, URA CNRS 1287, Université Joseph Fourier, Grenoble, France.
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Sulpice
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Boucher
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Pucheu
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de Leiris
D000818:Animals; D003250:Constriction; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008315:Malondialdehyde; D009195:Peroxidase; D007213:Indomethacin