Effects of blood flow on the in vivo recovery of a small diffusible molecule by microdialysis in human skin

被引:46
作者
Clough, GF
Boutsiouki, P
Church, MK
Michel, CC
机构
[1] Southampton Gen Hosp, Sch Med, Div Infect Inflammat & Repair, Southampton SO16 6YD, Hants, England
[2] Univ London Imperial Coll Sci Technol & Med, London, England
关键词
D O I
10.1124/jpet.102.035634
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to investigate the impact of changes in local blood flow on the recovery of a small, diffusible molecule (sodium fluorescein) from the extravascular tissue space of the skin, by microdialysis in vivo. Loss and recovery of fluorescein by linear microdialysis probes (5-kDa molecular mass cutoff, 0.2 mm diameter) inserted 1 mm apart in pairs, at three sites in the skin of the volar surface of the forearm of healthy volunteers, was measured under conditions of basal, reduced (noradrenaline, 0.005 mg/ml), and increased (glyceryl trinitrate, patch) blood flow. Whereas loss of tracer from the delivery probe appeared unaffected by changes in local blood flow, retrieval of fluorescein by the second probe was directly related to blood flux, measured using scanning laser Doppler imaging. Steady-state recovery at vasoconstricted sites was 4.0 +/- 0.7 mug . ml(-1) compared with 1.8 +/- 0.7 mug . ml(-1) at control sites (p < 0.001). Local vasodilatation reduced the retrieval of fluorescein by ∼50% to give a steady-state concentration of fluorescein in the dialysate at 40 to 50 min after the start of perfusion of 0.9 +/- 0.3 μg . ml(-1) (p = 0.05). These studies in the skin are consistent with microdialysis theory. They suggest that clearance of solute by the blood will have a significant impact on microdialysis probe recovery and that, in the skin, the magnitude of this clearance is directly related to blood flow.
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页码:681 / 686
页数:6
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