CALCULATION OF PLASMA-CONCENTRATIONS OF INTRAARTERIALLY INFUSED COMPOUNDS IN FOREARM PLETHYSMOGRAPHY

Objective: Forearm blood flow plethysmography is a widely accepted in vivo technique for pharmacologic and functional studies in peripheral resistance vessels and veins. Pharmacological effects on forearm blood flow (FBF) are usually expressed by means of dose-response relationsh ips. This approach does not consider the influence of variations in FB F on the actual plasma concentrations of compounds infused, and is les s suitable for quantitative comparison of the pharmacologic characteri stics of different compounds. The aim of this study was to validate an equation to estimate the plasma concentrations of intra-arterially in fused compounds. This was done at different levels of FBF, using an in dicator dilution technique with constant rate infusions of indocyanine green (ICG) and inulin, Methods: ICG (0.5 mg/min) and inulin (5 mg/mi n) were infused into the brachial artery in the presence of sodium nit roprusside (10 ng/kg/min; to obtain high FBF), vehicle (0.9% saline; f or intermediate FBF), and methoxamine (1 mu g/kg/min; for low FBF). FB F was measured using venous occlusion plethysmography in six healthy m ale volunteers. Plasma concentrations of the indicators, measured in v enous blood samples, were compared with the calculated values. Results : Excellent correspondence was observed between calculated and measure d plasma concentrations for both ICG and inulin. Venous plasma concent rations of ICG (greater than or equal to 95% protein binding) reached steady-state within four min independent of FBF. Alternatively, the ti me required for venous plasma concentrations of inulin (not bound to p rotein) to reach steady-state appeared dependent on FBF. Conclusion: T otal plasma concentrations of intra-arterially infused drugs can be ap propriately estimated at the level of the arterioles by the proposed e quation. (C) 1998 Elsevier Science B.V.