title: Effect of postconditioning on myocardial 99mTc-annexin-V uptake: comparison with ischemic preconditioning and caspase inhibitor treatment.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan. taki@med.kanazawa-u.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Taki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kawashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Daiki
authors.initials: D
authors.lastname: Kayano
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Tait
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsunari
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Seigo
authors.initials: S
authors.lastname: Kinuya
authors.forename: H William
authors.initials: HW
authors.lastname: Strauss
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats
chemical_list: D017304:Annexin A5; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C417036:technetium Tc 99m annexin V