99mTc-Annexin-V Uptake in a Rat Model of Variable Ischemic Severity and Reperfusion Time

Abstract

To determine whether mild to moderate ischemia that is not severe enough to induce myocardial infarction will cause myocardial cell damage or apoptosis, the (99m)Tc-Annexin-V (Tc-A) uptake was studied in groups of rats with various intervals of coronary occlusion and reperfusion times. After left coronary artery occlusion for 15 min (n=23), 10 min (n=23), or 5 min (n=12), Tc-A (80-150 MBq) was injected at 0.5, 1.5, 6, or 24 h after reperfusion. One hour later, to verify the area at risk, (201)Tl (0.74 MBq) was injected just after left coronary artery re-occlusion and the rats were killed 1 min later. Dual tracer autoradiography was performed to assess Tc-A uptake and area at risk. In all 5-min occlusion and reperfusion models, no significant Tc-A uptake was observed in the area at risk. Tc-A uptake ratios in the 15-min and 10-min ischemia models were 4.46+/-3.16 and 2.02+/-0.47 (p=0.078) at 0.5 h after reperfusion, 3.49+/-1.78 and 1.47+/-0.11 (p<0.05) at 1.5 h after reperfusion, 1.60+/-0.43 and 1.34+/-0.23 (p=0.24) at 6 h after reperfusion, 1.50+/-0.33 and 1.28+/-0.33 (p=0.099) at 24 h after reperfusion, respectively. With 15-min ischemia, in 3 of the 5 rats there were a few micro-foci of myocardial cell degeneration and cell infiltration in less than 1% of the ischemic area at 24 h after reperfusion. No significant histological change was observed in rats with 10-min or 5-min ischemia. The data indicate that Tc-A binding depends on the severity of ischemia even without a significant amount of histological change or infarction.