| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
To determine whether cardio-protective interventions such as ischemic preconditioning, postconditioning, and suppression of apoptosis by caspase inhibitor suppress myocardial apoptosis, Tc-99m-annexin V (Tc-AV) imaging was performed in a rat model of 20min ischemia and reperfusion. After 20min of coronary occlusion and reperfusion, Tc-AV was injected at 30min and 90min after reperfusion. One hour later the coronary artery was re-occluded and thallium-201 was injected to delineated area at risk and the rats were sacrificed 1 min later. Dual tracer autoradiography was performed to assess Tc-AV uptake and area at risk. In control rats, significant Tc-AV uptake was observed within ischemic area (Tc-AV uptake ratio (ischemic to normal area's count density ratio) was 4.15±1.89, 3.70±1.41 at 30min and 90min after reperfusion, respectively). In rats with ischemic preconditioning the uptake ratio decreased significantly (1.17±0.29, 1.33±0.74, respectively). By postconditioning the Tc-AV uptake was also suppressed (2.09±0.56, 1.88±0.69, respectively). Caspase inhibitor treatment also reduced the uptake (2.08±0.50, 1.27±0.24, respectively). Two weeks after reperfusion, Tc-AV uptake was not observed in rats without myocardial thinning (1.01± 0.29), however, the significant Tc-AV uptake was observed in the area of wall thinning or remodeling (1.71± 0.34). In conclusion, myocardial remodeling after ischemia may be related to apoptosis. Apoptosis can be suppressed by the cardio-protective interventions and Tc-AV imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning and antiapoptotic therapy.
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