This project has as long-term objective the differential control of conduction in peripheral nerve fibers. The goal of the continuation period (years 07-09) is to acquire the data necessary to realize an innovative pharmacokinetic method of accurately controlling clinical subarachnoid blockade. The guiding model comprises two compartments, the cerebrospinal fluid (CSF) and the nerve roots, and specifies conduction blockade by means of the equation of single myelinated fiber conduction block recently developed in this research. The model calculates the dosage that is necessary to depress and maintain the safety factor of conduction below criterion in the myelinated fibers of the highest segmental nerve root supplying the field of operation. Decremental conduction then automatically insures that blockade of the caudad segmental nerve roots is present as well. Prior to actual clinical application, however, the model requires much fresh information on several of the compartmental parameters, which will be obtained in this project as follows: (i) volume of the spinal CSF, derived from magnetic resonance imaging on volunteers (ii) lengths, weights and volumes of intrathecal thoracic, lumbar and sacral nerve roots, measured directly on human autopsy material; (iii) uptake of local anesthetic from CSF by spinal nerve roots and dura mater, measured on human autopsy material by tracer methods or combined gas chromatography-mass spectrometry, and calibrated on animal material taken before and after death; (iv) capillary density in the nerve roots, dura mater and spinal cord white matter, determined in sections stained for factor VIII by an immunohistochemical method, to serve as an index of relative elimination of drug from these tissues by the circulation. With these data the model will be able to calculate the dosages for single and continuous administration, and present them to the anesthesiologist on a simple pharmacokinetic diagram.
NIH ExPorter
NIH ExPorter