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

Abstract

99m Tc-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 99m Tc-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 5 13), after thoracotomy the left coronary artery was occluded for 20 min followed by reperfusion for 30 or 90 min and injection of 99m Tc-annexin-V (80-150 MBq). One hour later, to verify the area at risk, 201 Tl (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 5 11) was performed just after the reperfusion, and preconditioning (n 5 11) and caspase inhibitor treatment (n 5 11) were performed before ischemia. Dual-tracer autoradiography was performed to assess 99m Tc-annexin-V uptake and area at risk. Results: In all control rats, intense 99m Tc-annexin-V uptake was observed in the area at risk (uptake ratios at 30 or 90 min after reperfusion, 4.15 6 1.89 and 3.70 6 1.41, respectively). Postconditioning suppressed 99m Tc-annexin-V uptake (uptake ratios at 30 or 90 min after reperfusion, 2.09 6 0.56, P , 0.05, and 1.88 6 0.69, P , 0.05, respectively). Preconditioning also suppressed uptake (uptake ratios at 30 and 90 min after reperfusion, 1.17 6 0.29, P , 0.005, and 1.33 6 0.74, P , 0.01, respectively), as did caspase inhibitor (uptake ratios at 30 and 90 min after reperfusion, 2.08 6 0.50, P , 0.05, and 1.27 6 0.24, P , 0.005, respectively). In all interventions, the percentage of cells positive on deoxyuride-59-triphosphate biotin nick end labeling and histologic changes with myocardial cell degeneration and cell infiltrations were suppressed markedly. Conclusion: These data indicate that 99m Tcannexin-V imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning, and antiapoptotic therapy.

14C-Methionine Uptake as a Potential Marker of Inflammatory Processes After Myocardial Ischemia and Reperfusion

“…After a 30-min interval of LCA occlusion, reperfusion was obtained by release of the snare and confirmed by a myocardial blush over the area at risk. The snare was left loose on the surface of the heart until just before sacrifice, when it was retightened to identify the area at risk (10). Groups of animals were studied at 1 (n 5 6), 3 (n 5 5), 7 (n 5 5), 14 (n 5 6), and 28 d (n 5 6) after reperfusion.…”

Dynamic Expression of Tenascin-C After Myocardial Ischemia and Reperfusion: Assessment by 125I-Anti–Tenascin-C Antibody Imaging

“…The 125 I-TNC-Ab uptake ratio was calculated by dividing the uptake value in an ischemic area by that of a normally perfused area. The ratio of a 125 I-TNC-Ab uptake ROI to an ischemic ROI was defined as the percentage of the 125 I-TNCAb uptake area (18). All parameters in each rat were expressed as the average value obtained from the analysis of 3 representative slices.…”

“…Reperfusion was obtained by release of the snare and was confirmed by a myocardial blush over the area at risk. The snare was left loose on the surface of the heart until repeated thoracotomy for reocclusion of the LCA just before sacrifice to identify the area at risk (18). Groups of animals with 20 min of occlusion were studied at 1 d (n 5 6), 3 d (n 5 5), and 7 d (n 5 5) after reperfusion, and groups of animals with 30 min of occlusion were studied at 1 d (n 5 6), 3 d (n 5 6), 7 d (n 5 5), 14 d (n 5 6), and 28 d (n 5 6) after reperfusion.…”

Creation of clinically relevant model of chronic heart failure: Application of multi-modality imaging to define physiology

“…Additionally, due to the non-invasive technique of these imaging tools, their model and imaging approach can provide a means to evaluate the progression of HF and to quantify the temporal changes in flow and metabolism. In addition to the information provided on perfusion and metabolic outcomes, additional imaging could be applied to interrogate regional activation of critical receptors or enzymes within the myocardium, [24][25][26][27][28] neurohormonal changes, [29][30][31][32][33] along with regional changes in myocardial hypoxia, 34 apoptosis, 35,36 necrosis, 37 and fibrosis. 38 Unfortunately, the current study reported a high attrition (overall survival rate of 26%) with a major cause of death attributable to lethal arrhythmias during the perioperative period.…”