| Project/Area Number |
10671091
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SATO Akira Graduate Sch. of Medicine, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (20250764)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Syukichi Graduate Sch. of Medicine, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (50282075)
KUROKAWA Yoshimochi Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (80215087)
OHKOHCHI Nobuhiro Graduate Sch. of Medicine, Tohoku Univ., Associate Prof., 大学院・医学系研究科, 助教授 (40213673)
ANDO Kenjiro Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (40261614)
桜田 正寿 東北大学, 医学部附属病院, 助手 (40292320)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Nitroglycerin / Peripheral vascular disease / Chronic limb ischemia / transdermal administration / Transcutaneous oxygen tension / Transcutaneous bicarbonate tension / Laser Doppler velocimetry / Near-infrared spectroscopy / 経皮投与 |
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| Research Abstract |
We evaluated the effects of locally applied transdermal nitroglycerin (NTG) for the treatment of chronic limb ischemia due to peripheral vascular disease, using 1) transcutaneous PO2/PCO2 tension (tcPO2/tcPCO2) measurement in 15 patients, 2) treadmill walking test with near-infrared spectroscopy (NIRS) in 25 patients, 3) cutaneous blood flow and temperature measurement using laser Doppler velocimeter in 9 patients, and 4) measurement of blood concentration of NTG, simultaneously with tcPO2/PCO2 and cutaneous blood flow measurements. Five milligram NTG patches or 12 mg NTG ointments were applied to the ischemic legs.
TcPO2 significantly increased from 24.3【minus-plus】19.6 mmHG to 41.1【minus-plus】22.0 mmHg (p<0.0001) and tcPCO2 significantly decreased from 50.1【minus-plus】8.54 mmHg to 44.5【minus-plus】5.53 mmHg (p<0.001) by local application of NTG patches. Recovery-time of oxyHb measured by NIRS significantly reduced, when NTG patches were applied to measured legs (3.65【minus-plus】2.06 mi
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nutes, p<0.05) and contralateral legs (3.84【minus-plus】2.20 min., p<0.05), compared with when which were not (4.26【minus-plus】2.60 min.). The cutaneous blood flow of the NTG applied legs significantly increased from 101±66 BPU to 196±116 BPU (p<0.01) and the cutaneous temperature significantly elevated from 30.5【minus-plus】1.0℃ to 34.2【minus-plus】1.2℃ (p<0.001) by application of NTG ointments. The cutaneous blood flow of the contralateral legs with no treatment did not significantly changed by application of NTG ointments, while the temperature significantly elevated from 32.0【minus-plus】1.0℃ to 34.2【minus-plus】1.3℃ (p<0.05). The NTG blood concentration of the femoral vein of the patches applied legs was 1.69【minus-plus】1.67 ng/ml and 9.99【minus-plus】7.16 ng/mg, respectively 30 min. and 120 min. after the application, whereas that of the cubital vein was not detectable. The NTG blood concentration of the femoral vein of the ointments applied legs was 23.55【minus-plus】27.46 ng/ml 120 min. after the application, significantly higher than that of the cubital vein (0.40【minus-plus】0.22 ng/ml), (p<0.05).
We speculate that nitric oxide produced from NTG, which exists in high concentration within ischemic legs, enhances circulation and provided beneficial effects. In conclusion, the local transdermal administration of NTG to ischemic limb is a useful therapeutic method for the treatment of peripheral vascular disease, and the administration at the site of ischemia could provides larger effects than that at other sites. Less
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