No effect of circulating drug upon isolated forearm block

Controversy exists as to whether the recovery of isolated arm blockade is primarily determined by resultant plasma drug concentrations, or by the affinity of the drug for the biophase. We have investigated the effect of the circulating drug produced by the isolated forearm experiment upon its recovery profile. Paralysis from retrograde spread of drug after the intravenous injection of 20 ml saline containing vecuronium 0.3 mg into a forearm isolated from the circulation was achieved in three groups of five experiments. Group 1 were used as controls, the tourniquet being released after 3-4 min and the recovery of block observed. In group 2 the tourniquet was similarly released but a repeat dose of vecuronium 0.3 mg was administered into the systemic circulation at 10% recovery. In group 3 the tourniquet was released at 50% twitch depression and the repeat dose of vecuronium 0.3 mg given when the twitch height had recovered to that level. The mean (SD) 25% to 75% recovery indices of groups 1, 2 and 3 were: 9.2 (2.4), 8.7 (1.2) and 9.9 (1.9) min. There was no noticeable effect on the recovery slope of any of the traces when the second dose of myoneural blocker was given systemically in groups 2 and 3. The findings indicate that the main determinant of recovery of the isolated forearm experiment is not its plasma drug concentration but a mechanism which maintains the drug in the effect compartment.