Effects of nafazatrom and indomethacin on experimental myocardial ischemia in the anesthetized dog.
The anti-ischemic effects of nafazatrom (10 mg/kg intraduodenally) have been studied in a canine model of myocardial infarction. Nafazatrom was given 30 min before and 2 h after occlusion of the left anterior descending coronary artery (LAD). Effects were compared with those after intravenous indomethacin (10 mg/kg) treatment. Infarct size was measured at 6 h of coronary occlusion by postmortem tetrazolium staining. Myocardial ischemia was reduced after nafazatrom administration, whether related to total left ventricle (18 +/- 3.3 vs. 30.7 +/- 4.8%; p less than 0.05) or to the LAD vessel area at risk for infarction (51.4 +/- 4.0 vs. 82.5 +/- 4.5%; p less than 0.01). Salvage with nafazatrom occurred in the subepicardial and endomural tissues without lateral protection. Indomethacin had no effects on infarction. The LAD occlusion-induced hemodynamic consequences were reduced at 15 min by nafazatrom and remained unchanged by indomethacin. During the following experimental course, no differences were noted between the groups. At 6 h, blood flow in the nonoccluded circumflex artery increased by 12.6 +/- 3.2 ml/min (p less than 0.05) following nafazatrom treatment. Thus, nafazatrom reduced ischemia by a mechanism unrelated to changes in hemodynamics. Most likely, this was due to 5-lipoxygenase inhibition. This may shift arachidonic acid metabolism to cyclooxygenase products and prevent release of deleterious lipoxygenase products by neutrophils during ischemic injury.
Fiedler
V B
VB
Mardin
M
M
D000758:Anesthesia; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D011720:Pyrazoles / Q000627:therapeutic use*; D047069:Pyrazolones
D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; C018845:nafazatrom; D007213:Indomethacin