Limiting lipid peroxidation in the nonischemic zone of infarcted rat hearts by indomethacin improves left ventricular function without affecting myocardial healing and remodeling.
We recently showed that indomethacin reduces lipoperoxidation occurring in the nonischemic zone (right ventricle + septum; RVS) of rat hearts with permanent coronary occlusion. The purpose of this study was to determine whether this biochemical effect is associated with an improvement of residual cardiac function or with modifications of delayed ventricular remodeling, or both. Rats received either indomethacin (1 mg/kg i.p.) or a placebo 5 min before coronary occlusion, and then twice a day for 48 hours. Six hours after ligation, myeloperoxidase (MPO) activity (leukocyte infiltration index) was measured in the ischemic zone (left ventricle; LV) and in RVS. Forty-eight hours after ligation, left ventricular function was assessed in vivo. Alterations in myocardial geometry were estimated 21 days after ligation on histologic cross-sections. In the indomethacin group, cardiac function was improved compared with that with placebo, and the indexes of ventricular remodeling were not affected by the treatment. Finally, indomethacin at the dose used did not affect MPO activity in the LV. It is concluded that indomethacin treatment leads to a better maintenance of residual nonischemic tissue contractility without worsening late ventricular shape changes. These results could in part be explained by the ability of the treatment to decrease inflammatory mediator-induced oxidative stress in RVS without affecting infarct healing caused by leukocyte infiltration in LV.
Sulpice
T
T
Physiopathologie Cellulaire Cardiaque, Université Joseph Fourier, France.
Boucher
F
F
de Leiris
J
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D007213:Indomethacin / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects; D008026:Ligation; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin