| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Seiji Kagawa Medical University Associate Professor, 医学部・附属病院, 講師 (60253267)
MIZUSHIGE Katsufumi Kagawa Medical University Associate Professor, 医学部, 助教授 (90166009)
SENDA Shoichi Kagawa Medical University Professor, 医学部附属病院, 教授 (30145049)
NOZAKI Shiro Kagawa Medical University Assistant Professor, 医学部・附属病院, 助手 (80243773)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Research Abstract |
1) Arterial Wall Distensibility During Prestage of Type 11 Diabetes Mellitus in Rats
Aortic damage during prestage of diabetes mellitus (DM) was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type 11 DM. Methods : In 30 OLETF and 30 nonDM rats, an oral glucose tolerance test was performed at 10, 20 and 30 weeks of age. At 15 and 30 weeks, intravascular ultrasound images and aortic pressure were recorded. Aortic diameter was measured on the largest and the smallest images during the cardiac cycle and the stiffness parameter β was calculated. The aortic walls were excised for histopathology and the measurement of hydroxyproline at 5, 15 and 30 weeks. At 10 weeks, blood glucose (mg/dl) levels of the OLETF (baseline; 115 ± 7, 2 hrs ; 168 ± 30) were higher than those of the nonDM rats (baseline ; 87 ± 5, 2 hrs ; 118 ± 15 ; p=.02), and plasma insulin concentrations (ng/ml) were higher in the OLETF rats (2 hrs ; 0.82 ± 0.15) than those in the nonDM rats (
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2 hrs ; 0. 16 ± 0.64 ; p=.003). At the prediabetic stage (15 weeks), P in OLETF rats (2.5 ± 0.9) was larger than in nonDM rats (1.4 ± 0.4; p=.0006), and the collagen (hydroxyproline) content /dry weight (mg/g) of the aortic wall was significantly higher in the OLETF rats (33.5 ± 3.1) than in the nonDM rats (28.7 ± 3.5 ; p<.05). Histopathological examination showed that from 15 weeks medial wall thickness increased gradually. Hyperinsulinemia may induce changes in the extracellular matrix and impair aortic wall distensibility prior to the development of type II DM..
2) Coronary Arterial Tone and Autonomic Nerve System
The purpose of this study was to assess the role of the autonomic nervous system in the regulation of basal coronary artery tone in normal and atheromatous segments using intravascular ultrasound in humans. In each of twenty two patients, one site of coronary artery was evaluated by means of a 3.2 F, 30-MHz intravascular ultrasound before and after intracoronary administration of 2 mg isosorbide dinitrate (ISDN). We identified the perimeter of the vessel wall with normal or atherosclerotic plaque on ultrasound image. Segmental perimeter for each normal or plaque segment at eccentric plaque site and circumferential perimeter at normal or concentric plaque site and circumferential perimeter at normal or concentric plaque site were measured, and percent change in each perimeter produced by ISDN was calculated. Using heart rate variability analysis on 512 seconds recorded immediately before ISDN administration, cardiac sympathetic and vagal activities were evaluated as the integrated power of the low-frequency (LF : 0.04 to 0.15 Hz ), and high-frequency (HF : 0.15 to 0.4 Hz) spectral components, respectively. ISDN produced increase in the perimeter of the vessel wall in all of 22 sites. A significant correlation of the increase in perimeter by ISDN to the power of HF (r=0.749, p<.001) was observed at 16 normal segments despite no significant correlation to LF. At 13 atheromatous segments, no significant correlation between the morphology and autonomic nerve activity was observed. Basal tone of normal coronary segments by ultrasound are regulated by parasympathetic nerve at rest, whereas the regulation is impaired in mild atherosclerotic segment. Less
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