| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Whether geranylgeranylacetone (GGA), an antulcer drug reported to induce the heat-shock protein 70 family, may produce mycardial protection was inverstigated using an in vivo model of rabbit. The influence of anesthetics on cardioprotection by GGA was also evaluated. The infact size and the area at risk of ischemia were measured by triphenyltetrazolium chloride and Evans blue dyeing. Integrated backscatter (IBS) images of left ventricular short-axis view level were obtained and myocardial tissue ultrastrucural integrity was evaluated using the magnitudes of cyclic variation of IBS (MCV).
[2001] Each of 1 mg/kg GGA was intravenously administered 12 hrs before and just before experiment (GGA group, n=6). The ischemic preconditioning (IP) group (n=8) was preteated with two 5-min anterolateral coronary occlusions interspersed with 15-min periods of reperfusion. All groups underwent 30 min of coronary occlusion, followed by 180 min of reperfusion. The ratios of infact size to risk area in GG
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A and IP groups (36.6^^+__-17.9%, 31.3^^+__-9.1%) were significantly lower than that in control group (59.2^^+__-18.3%, n=7). MCV significantly decreased after coronary occlusion in all groups, however there was no significant differenca between each group.
[2002] Vehicle or GGA at a dose of 10 mg/kg was intravenously given 24 hrs before experiment (GGA group, n=8, vehicle group, n=7). After pretreatment with GGA, GGA+5HD group (n=8) received the mitochondrial adenosine triphoshate-sensitive potassium (K_<ATP>) channel blocker, sodium 5-hydroxydecanote (5mg/kg) 30 min before coronary occlusion. In GGA+SEV group (n=8), sevoflurane (0.5 MAC) was administered 60 min before occlusion and continued for 30 min. all groups underwent 30 min of coronary occlusion, followed by 180 min of reperfusion. The ratios of infarct size to risk area in GGA and GGA+SEV groups (38.5^^+__-9.9%, 26.9^^+__-19.7%) were significantly lower compared with those in vehicle and GGA+5HT groups (59.2^^+__-9.4%, 55.2^^+__-13.7%).
GGA produced myocardial protection as IP, which was enhanced with sevoflurane inhalation. The mechanism of GGA-induced cardioprotection may involve the mitochondrial K_<ATP> channel. Less
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