Cochlear Fluids Simulator - Example Output

Mini-Osmotic Pump Simulation

1) Simulation of drug delivery by mini-osmotic pump into scala tympani of the guinea pig cochlea. Diffusion is based on a solute with formula weight of 1000 (a small peptide) with diffusion coefficient estimated to be 0.54 x 10-5 cm2/s. The gray triangle shows the site of fluid entry delivered by the pump, 4 mm from the base of scala tympani. The gray rectangle indicates the site of fluid exit, assumed to be the cochlear aqueduct at the base of scala tympani. An application rate of 0.1 ul/min (i.e. 6 ul/hour) is simulated. The distrubution of drug is shown at 60 minutes after injection starts (longer times can also be simulated) The orange triangle indicate the site at which solute concentration is measured as a function of time (data not shown).

The figure shows that diffusion towards the apical regions of the cochlea is extremely slow. As a result, if there is any clearance of the drug (by metabolism, binding to tissues, clearance to other scalae or to the vasculature) then the drug may never reach the apical regions of the cochlea in appreciable concentrations. The simulator allows the effects of different clearance rates to be evaluated.

 

2) Same conditions as Figure 1, above, but showing the simulator's display of concentration as a function of distance along each scala. The numeral at the left of each plot indicates the full-scale concentration for that plot in arbitrary units. The injection solution has a concentration of 1000 Units/volume (e.g. 1000 uM). The solute present in scala vestibuli is the result of the known cross-communication between ST and SV across the spiral ligament, which has been incorporated into this simulation.

 

3) Same simulation as Figure 1, above with an added small perilymph leak at the site of entry of the cannula in scala tympani. A perilymph leak rate of 0.2 ul/min is simulated, with perilymph replaced by cerebrospinal fluid entering the base of scala tympani via the cochlear aqueduct. Note that a small leak will have a dramatic effect on the drug concentration achieved.