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.