Effects of flurbiprofen in altering the size of myocardial infarcts in dogs: reduction or delay?
Anti-inflammatory agents such as flurbiprofen have been claimed to reduce infarct size in a number of models of coronary artery occlusion. However, several of the studies are controversial and also do not allow the critical distinction between reducing and delaying injury. In the present study, a closed chest method of coronary occlusion was used to generate small areas of regional myocardial ischemia in dogs. The method involved cannulation of the coronary ostium by way of the carotid artery and coronary embolization with 2.5 mm diameter beads. Flurbiprofen (1 mg/kg) was given immediately after occlusion and thereafter every 6 hours. Groups of dogs were subjected to either 6 or 24 hours of elapsed ischemia, after which time the hearts were removed and sectioned. Frozen-tissue slices were stained with triphenyl tetrazolium in order to delineate infarct size. After staining the tissue slices were subjected to autoradiography in which microspheres given immediately after occlusion were visualized to delineate the perfusion bed served by the occluded coronary artery (zone at risk). Risk zone to infarct size ratios for drug treated and control animals revealed that flurbiprofen treatment had no effect upon infarct size as determined 24 hours after occlusion. Despite significant residual coronary flow in the ischemic area, virtually all of the risk zone deteriorated to necrotic tissue. By contrast, after 6 hours of elapsed ischemia, infarct size was considerably reduced in the flurbiprofen-treated group. With the proviso that the drug might have affected only the sensitivity to tetrazolium staining, these results indicate that in severe ischemia, flurbiprofen can greatly delay but not prevent tissue necrosis.
D000818:Animals; D001345:Autoradiography; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D005480:Flurbiprofen / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D011422:Propionates / Q000627:therapeutic use*
D011422:Propionates; D005480:Flurbiprofen