Infarct-size limitation--real or artifactual. Studies with flurbiprofen using a reperfusion model

With the use of tetrazolium staining and risk-zone analysis, flurbiprofen has previously been shown to limit infarct size at 6 hr but not at 24 hr following coronary embolization in the dog heart. This study was designed to assess whether this delay in the development of a histologically defined infarct was real or an artifact arising from the effect of the drug on tetrazolium staining characteristics. With the use of a closed-chest bead-embolization model with a capability for reperfusion, hearts were made ischemic for 4 hr by injecting a 2.5 mm bead attached to a silk thread through a special cannula into the coronary vasculature. Immediately following occlusion, radioactive microspheres (141Ce) were administered to define the zone at risk of infarction. Hearts were divided into treatment (flurbiprofen, 1 mg/kg every 6 hr, N = 7) and control (saline, N = 7) groups. Following 4 hr of ischemia, the ischemic area was reperfused by withdrawing the thread and attached bead. Twenty hours later, the hearts were removed and transverse sections (3 mm) were prepared. The area of necrosis was visualized by tetrazolium staining and the risk zone by microsphere autoradiography. In control hearts, 24.7 +/- 5.0% of the zone at risk deteriorated to necrotic tissue; in the flurbiprofen-treated hearts, 17.4 +/- 4.3% of the risk zone became necrotic (NS, p greater than 0.10). Thus, despite earlier findings, these results suggest that the apparent delay in the development of tissue injury may be artifactual.