Effect of Postconditioning on Myocardial 99mTc-Annexin-V Uptake: Comparison with Ischemic Preconditioning and Caspase Inhibitor Treatment

Journal of Nuclear Medicine

Atsuhiro Kawashima¹  Takahiro Higuchi¹  Seigo Kinuya¹  Daiki Kayano¹  Kenichi Nakajima¹  Ichiro Matsunari¹  Jonathan F. Tait¹  Makoto Fukuoka¹  H. William Strauss¹  Junichi Taki¹ 

关键词: ^99mTc-annexin-V;    postconditioning;    ischemic preconditioning;    apoptosis imaging;    caspase inhibitor;   

DOI  :  10.2967/jnumed.106.037408

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

99mTc-Annexin-V imaging has been proved to be feasible to detect phosphatidylserine, which externalizes on the outer cell membrane early in the process of apoptosis. To determine whether postconditioning suppresses myocardial cell damage or apoptosis, we evaluated the intensity and distribution of 99mTc-annexin-V uptake after postconditioning in a rat model of ischemia and reperfusion and compared the effect to that of ischemic preconditioning and pretreatment with caspase inhibitor. Methods: In control rats (n = 13), after thoracotomy the left coronary artery was occluded for 20 min followed by reperfusion for 30 or 90 min and injection of 99mTc-annexin-V (80–150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just beyond the left coronary artery reocclusion, and the rats were sacrificed 1 min later. In the groups of rats with various interventions, postconditioning (n = 11) was performed just after the reperfusion, and preconditioning (n = 11) and caspase inhibitor treatment (n = 11) were performed before ischemia. Dual-tracer autoradiography was performed to assess 99mTc-annexin-V uptake and area at risk. Results: In all control rats, intense 99mTc-annexin-V uptake was observed in the area at risk (uptake ratios at 30 or 90 min after reperfusion, 4.15 ± 1.89 and 3.70 ± 1.41, respectively). Postconditioning suppressed 99mTc-annexin-V uptake (uptake ratios at 30 or 90 min after reperfusion, 2.09 ± 0.56, P < 0.05, and 1.88 ± 0.69, P < 0.05, respectively). Preconditioning also suppressed uptake (uptake ratios at 30 and 90 min after reperfusion, 1.17 ± 0.29, P < 0.005, and 1.33 ± 0.74, P < 0.01, respectively), as did caspase inhibitor (uptake ratios at 30 and 90 min after reperfusion, 2.08 ± 0.50, P < 0.05, and 1.27 ± 0.24, P < 0.005, respectively). In all interventions, the percentage of cells positive on deoxyuride-5′-triphosphate biotin nick end labeling and histologic changes with myocardial cell degeneration and cell infiltrations were suppressed markedly. Conclusion: These data indicate that 99mTc-annexin-V imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning, and antiapoptotic therapy.

【 授权许可】

Unknown