2000 Fiscal Year Final Research Report Summary
INTRACELLULAR EFFECTS OF ANESTHETICS ON THE CONTRACTION AND RELACATION OF VASCULAR SMOOTH MUSCLES
| Project/Area Number |
11671505
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
KANMURA Yuichi FACULTY OF MEDICINE, KAGOSHIMA UNIVERSITY, PROFESSOR, 歯学部, 教授 (30211189)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ANESTHETICS / VASCULAR SMOOTH MUSCLE / α2AGONIST / DEXMEDETOMIDINE / SEPTIC SHOCK / OLPRINONE |
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| Research Abstract |
To investigate the direct effects of dexmedetomidine(DEX) on human resistance arteries in vitro, mechanical responses evoked from human gastroepiploic arteries were recorded. In endothelium-denuded rings, DEX(in concentrations found in the plasma in clinical usage ; 10^<-10> to 10^<-8>M) neither elicited any direct vascular effect nor modified 1 μ M norepinephrine(NE)-, 1 μ M phenylephrine(PE)-, or 40mM K^+-induced contractions. A high concentration of DEX(10^<-5>M) induced a small contractile response weaker than that induced by clonidine. In higher doses(10^<-7> to 10^<-5>M), DEX enhanced both K^+-induced contraction and the contraction induced by Ca^<2+> during membrane depolarization, but it strongly attenuated both NE-induced and PE-induced contractions. These results indicate that in human vascular smooth muscle : 1) the plasma concentrations of DEX achieved in clinical usage may have a negligible direct vasoactive effect, and 2) pharmacological high dosed of DEX may modify vascular regulatory processes, presumably by enhancing Ca2+ influx and by blocking adrenergic agonist-mediated contractile pathway.
We also investigated the effects of endotoxin (lipopolysaccharide : LPS) on hepatic blood flow and systemic hemodynamics. Continuous infusion of LPS caused significant reductions in hemodynamic variables(cardiac output, systeic blood pressure, hepatic arterial blood flow, portal venous blood flow) and a significant increase in arterial lactate. Phosphodiesterase III inhibitor : olprenine halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery.
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