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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: The data indicate that Tc-A binding depends on the severity of ischemia even without a significant amount of histological change or infarction.