| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
We examined whether a caspase inhibitor can block apoptotic death of granulation tissue cells. myofibroblasts in particular, which proliferate in myocardial infarct area during subacute phase of myocardial infarction(MI)and disappear via apoptosis at chronic phase of MI, and thereby whether the blockade can prevent post-infarct heart failure accompanied by left ventricular(LV)remodeling. Intraperitoneal injection of pan-caspase inhibitor, Boc-Asp-FMK(BAT, 10 microg/kg)was started on the 3rd day after MI, which was produad by 60-min left coronary ligation and reperfusion using rats. BAF was injected every day until the rats were sacrificed on 2 weeks(n=5), or until 4 weeks post-MI in case the rats were sacrificed on12 weeks after MI(n=5). Controls was the rats with MI treated with vehide(n=5, each). At 2 weeks after MI, infarct area of the rats treated with BAF had significantly fewer TUNEL-positive granulation tissue cells(0.69 ± 0.03%)compared with that of controls(1.87 ± 0.30%), indicating that BAF is effective in blockade of apoptosis of granulation tissue cells. At 12 weeks after MI, examinations by echocardiography and Millar transducer catheter revealed that contorol rats showed severe heart failure with LV remodeling while BAF treatment significandy attenuated it as indicated by improved parameters of LV wall thickness(0.80±0.10 vs 1.06±0.20 mm), LV dilatation(12.2±0.57 vs 9.53±0.41 mm), LV contractility(%FS : 10.5 ± 2.7 vs 15.4 ± 2.1%, dP/dt : 4116 ± 622 vs 5159 ± 679 mmHg/sec), and LV end-diastolic(19.5 ± 6.02 vs 11.2 ± 1.92 mmHg)and central venous pressures(5.7 ± 1.0 vs 1.8 ± 0.8 mmHg). The present findings suggest that treatment with caspase inhibitor to subacute phase MI may be beneficial to prevent post-infarct heart failure accompanied with LV remodeling.
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