Defining the concentration-effect relationship of volatile anesthetics in vessels using an in vitro nonsteady-state...

We compared traditional steady-state experiments with nonsteady-state experiments in defining the vasodilating potency of isoflurane in isolated cerebral vessels. The effects of volatile anesthetics on isolated arterial vessel wall tension are typically examined by means of steady-state methodology. This requires the prolonged administration of the agent under study until a stable wall tension is achieved. An alternative, non-steady-state approach to such experiments is proposed as an adjunct technique to help simplify and in some cases evaluate more fully vascular response. Cylindrical segments of the rabbit basilar artery were placed into a perfused tissue bath, stretched to a resting tension of approximately 2000 dynes and then constricted with 30 nM K+. Thirty minutes later, 2.0 MAC of isoflurane was introduced into the fluid reservoir supplying the chamber. This administration was continued for 10 min, at which time isoflurane was discontinued and vessel tension was monitored for another 10 min. During this 20-min washin-washout period, samples of bath fluid were obtained q 1 min and isoflurane concentrations were subsequently determined by gas chromatography. After completion of these "nonsteady-state" measurements, another 30-min waiting period was allowed, after which vessels were exposed to stable concentrations of 0.5, 1.0, 1.5 and 2.0 MAC of isoflurane in varied order. Each exposure was for 15 min, with a 30-min agent-free rest period between exposures. An effect compartment model was selected for analysis of the nonsteady-state data. Ke0, a first order rate constant linking the concentrations in the bath to a theoretical effect compartment, was estimated by using a hysteresis minimization technique.(ABSTRACT TRUNCATED AT 250 WORDS)