The effect of indomethacin on cardiovascular and lysosomal mechanisms during experimental myocardial ischemia.
The present study evaluated the effects of indomethacin (INDO) on cardiovascular and lysosomal mechanisms during experimental myocardial ischemia (MI). INDO (5 mg/kg) was infused IV prior to MI, and the results were compared to vehicle-treated and sham-operated dogs. INDO induced a slight hypertension after MI. Additionally, INDO attenuated the decline in coronary blood flow in the non-ischemic myocardium after MI. Myocardial lysosomes (biopsied three hours post-MI) were more labile in ischemic than in nonischemic tissue, and INDO had a stabilizing effect on lysosomes from ischemic tissue. Plasma activity of cathepsin was increased following MI, and INDO attenuated this increase. In the myocardium (biopsies three hours post-MI) prostaglandin A + E levels were suppressed 60% in both ischemic and nonischemic tissue with INDO treatment; prostaglandin F2 alpha levels were lower with INDO treatment but not significantly so. These results suggest that INDO has a stabilizing effect on lysosomes in vivo, possibly involving an endogenous prostaglandin mechanism, and this protective effect may attenuate lysosomal damage to the cardiovascular system during MI.
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects*; D008297:Male; D013997:Time Factors
D003402:Creatine Kinase; D007213:Indomethacin