Osmotic pump implant for chronic infusion of drugs into the inner ear.
Continuous long-term delivery of experimental drugs to the cochlea of a small animal, such as a young guinea pig, presents several technical problems. A method of placing and securing a cannula-osmotic pump system is described in this paper. Guinea pigs (225-410 g) were unilaterally implanted with an Alzet micro-pump and cannula for delivery of 20 mM tetrodotoxin (TTX) (six animals) or saline (three animals) for three days (1 microliter/h). Auditory brainstem responses (ABRs) were recorded under light anesthesia on post-implant day 1 and day 3 and compared with pre-implant baseline values. In all six cochleas infused with TTX, most frequencies showed a 30-60dB decrease in sensitivity within 24 h. Saline control animals showed little or no change from baseline sensitivity for most frequencies. In three TTX-infused animals, the cannula-pump unit was removed on day 3, and ABRs were followed during recovery. Most frequencies returned to, or near, pre-implant levels after pump removal but recovery times varied. By day 6, all animals had recovered post-surgical weight loss and showed a gain of 10-40 g. Brains and cochleas were removed and processed for sectioning. Assessment of the cochlear nucleus of non-recovery TTX-treated animals showed a deafness-related flattening of auditory nerve active zones on the treated side.
Brown
J N
JN
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-05065.
Miller
J M
JM
Altschuler
R A
RA
Nuttall
A L
AL
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems; D005260:Female; D006168:Guinea Pigs; D015918:Infusion Pumps, Implantable; D008297:Male; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000008:administration & dosage*; D000159:Vestibulocochlear Nerve / Q000187:drug effects* / Q000502:physiology
D012462:Saline Solution, Hypertonic; D013779:Tetrodotoxin