| Project/Area Number |
03670431
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Hokkaido Univ. |
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Principal Investigator |
KOHYA Tetsuro Hokkaido Univ. School of Med. Instructor Medical Hospital, 医学部附属病院, 助手 (70205350)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAGUCHI Hideaki Hokkaido Univ. School of Med. Instructor Medical Hospital, 医学部附属病院, 助手 (70161297)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | hypertrophy (LVH) / SHR / regression of LVH / hypertension / sudden death / ACE inhibitor / Vf / アンジオテンシン変換酵素阻害薬 / 肥大の退縮 |
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| Research Abstract |
The purpose of the study is to test the hypothesis that regression of left ventricular hypertrophy (LVH) prevents sudden cardiac death caused by lethal ventricular tachyarrhytmias during acute ischemia. Hearts from spontaneously hypertensive rats (SIIR) were used as a model of hypertensive LVH and those from Wistar-Kyoto rats (WKY) were served as normotensive hearts. SHRs were divided into 3 groups, as follows: 1) SHRs with no treatment (SHR), 2) SHRs treated with captopril (SHR-C), 3) SHRs treated with hydralazine (SHR-H). The antihypertensive agents were given for 6 weeks, from 12 to 18 weeks of age. Experiments were performed at 18 weeks of age. Although blood pressure in SHR-C and SHR-H were equally lowered to normal level, only SHR-C showed regression of LVH. Lethal ventricular tachyarrhythmias induced during 30 minutes after ligation of the left coronary artery were studied in the 4 groups (WKY, SHR, SHR-C and SHR-H). The incidence of sustained ventricular tachycardia (VT) and ve
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ntricular fibrillation (Vf) was significantly higher in SHR with LVH than in WKY. Treatment with captopril significantly reduced the incidence of VT/Vf although hydralazine failed to reduce the incidence. The electrophysiological study using conventional microelectrode techniques revealed that in SHR and SHR-H with LVH, action potential duration (APD) was much more prolonged than in WKY while resting potential, action potential amplitude and maximum upstroke velocity of depolarization did not change significantly. The APDs in SHR and SHR-H with LVH shortened to a greater extent during simulated ischemia, while in SHR-C with regressed LVH APD shortened only a little similar to that in WKY. These results suggest that hypertrophied hearts have a greater susceptibility to lethal ventricular tachyarrhythmias during acute ischemia because of greater APDs dispersion between the normal and ischemic zone. The reduction of electrical inhomogeneity in regressd hypertrophied hearts may prevent sudden cardiac death caused by lethal ventricular tachyarrhythmias. Less
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