| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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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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