Contribution of protein kinases in the ischemic-induced dysfunction of cardiac sympathic innervation
| Project/Area Number |
08670755
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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 |
Circulatory organs internal medicine
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| Research Institution | Akita University |
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Principal Investigator |
ABE Toyohiko Akita Univ.School of Med.Assistant Professor, 医学部, 講師 (30231963)
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| Co-Investigator(Kenkyū-buntansha) |
KIBIRA Hitoshi Akita Univ.School of Med.Research Fellow, 医学部, 助手 (80234334)
SAITO Takashi Akita Univ.School of Med.Assistant Professor, 医学部, 講師 (90178484)
MIURA Mamoru Akita Univ.School of Med.Professor, 医学部, 教授 (10006710)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | TNF-alpha / neural stunning / 心臓交感神経 / 心筋虚血 / hydrocortisone / nerve growth factor / tumor necrosis factor-α / 副腎皮質ステロイド |
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| Research Abstract |
A brief period of myocardial ischemia is capable of producing transient dysfunction of cardiac sympathetic innervation. Tumor necrotizing facter-a (TNF-a) is a multifunctional cytokine that is also produced during myocardial ischemia and reperfusion. While TNF-a is reported to be a neurotrophic factor in the central nervous system, the protective role of TNF-a in cardiac neural stunning has not been determined. We examined the hypothesis that TNF-a attenuates post-ischemic reductions in sympathetic coronary constriction. Mongreldogs were anesthetized with a-chloralose and instrumented for recordings of heart rate (HR), arterial pressure (AP), LV dP dt, % segment length (%SL) and LAD and LCX coronary flow velocities (Doppler). After bilateral vagotomy and b-adrenergic blockade by propranolol, LAD was occluded for 15 min followed by reperfusion. Bilateral electrical stimulation of ansa subclavia was performed to evaluate % change in coronary resistance to sympathetic stimulation (D%CVR)
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before and after release of 15 min LAD occlusion. Intracoronary administration of TNF-a (6 ug/kg/min, n=6) or vehicle (n=5) was started 15 min before coronary occlusion to 5 min after reperfusion, In another dogs with intracoronary administration of anti-TNF-a antibody (60 nl/kg/mm, n=6) or vehicle (n=5), *%CVR was also estimated before and after release of 7 min LAD occlusion.
Results : 1) Sympathetic stimulation produced transient increase in coronary resistance in both LAD and LCX beds. *%CVR in the LAD bed before (40*8%, MSE) and 15 min after reperfusion (38*8%) was not different in dogs treated with TNF-a . This contrasts with the change in LAD resistance from dogs with vehicle (38*5% before and 162% after reperfusion ; p<0.05). 2) *%CVR in the LAD bed after release of 7 min LAD occlusion was not affected in dogs with vehicle, while it was decreased with anti-TNF-a antibody(38*5% before and 19* 8% after reperfusion ; p<0.05).
We conclude that TNF-a protects against post-ischemic neural stunning of sympathetic coronary innervation. Less
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Report
(4 results)
Research Products
(4 results)
