G J Carvalho1, A K Lalwani. 1. Department of Otolaryngology-Head & Neck Surgery, University of California, San Francicso, USA.
Abstract
HYPOTHESIS: Cochleostomy followed by intracochlear infusion, as a model system for continuous drug delivery, may be well tolerated by the auditory system with preservation of hearing. BACKGROUND: The infusion of therapeutic agents, such as neurotrophins, growth factors, anti-inflammatory drugs, and viral gene therapy vectors, into the cochlea over a prolonged period of time may be desirable to reduce cochlear damage after auditory insult. However, the effects of continuous cochlear infusion have not been studied adequately. METHODS: Eight Hartley guinea pigs underwent left cochleostomy with infusion of artificial perilymph (n = 7) or 0.85% saline (n = 1). The artificial perilymph or 0.85% saline was administered by an osmotic minipump (Alza, Palo Alto, CA, U.S.A., model 2002; infusion rate 0.5 microL/hr, mean pumping duration of 2.5 weeks) connected to the cochlea by a fine plastic cannula (Inner Diameter = 0.28 mm, Outer Diameter = 0.61 mm) that enters the scala tympani via a cochleostomy. Hearing was assessed by determining auditory brain stem response (ABR) thresholds before surgery and on postoperative days 3 and 7 for artificial perilymph infused animals and before surgery and on postoperative days 3, 7, 14, 21, and 28 for the single saline-infused animal. The ABR thresholds were determined with a click and at the following frequencies: 1 kHz, 2 kHz, 4 kHz, 8 kHz, 16 kHz, 20 kHz, and 30 kHz. RESULTS: There was a preservation of preoperative ABR thresholds in the lower frequencies (1, 2 kHz), mild elevation (< or =10 dB) in the midfrequencies (4, 8 kHz), and marked rise > or =>30 dB) in the ABR thresholds at higher frequencies (>16 kHz). Surprisingly, the single long-term animal showed recovery of hearing in midfrequencies and high frequencies with the passage of time. CONCLUSIONS: Cochleostomy and intracochlear infusion result in auditory insult limited largely to the region of surgical trauma. Demonstration of hearing preservation after surgical breach of the cochlea should encourage further development of potential diagnostic and therapeutic intervention into the inner ear.
HYPOTHESIS: Cochleostomy followed by intracochlear infusion, as a model system for continuous drug delivery, may be well tolerated by the auditory system with preservation of hearing. BACKGROUND: The infusion of therapeutic agents, such as neurotrophins, growth factors, anti-inflammatory drugs, and viral gene therapy vectors, into the cochlea over a prolonged period of time may be desirable to reduce cochlear damage after auditory insult. However, the effects of continuous cochlear infusion have not been studied adequately. METHODS: Eight Hartley guinea pigs underwent left cochleostomy with infusion of artificial perilymph (n = 7) or 0.85% saline (n = 1). The artificial perilymph or 0.85% saline was administered by an osmotic minipump (Alza, Palo Alto, CA, U.S.A., model 2002; infusion rate 0.5 microL/hr, mean pumping duration of 2.5 weeks) connected to the cochlea by a fine plastic cannula (Inner Diameter = 0.28 mm, Outer Diameter = 0.61 mm) that enters the scala tympani via a cochleostomy. Hearing was assessed by determining auditory brain stem response (ABR) thresholds before surgery and on postoperative days 3 and 7 for artificial perilymph infused animals and before surgery and on postoperative days 3, 7, 14, 21, and 28 for the single saline-infused animal. The ABR thresholds were determined with a click and at the following frequencies: 1 kHz, 2 kHz, 4 kHz, 8 kHz, 16 kHz, 20 kHz, and 30 kHz. RESULTS: There was a preservation of preoperative ABR thresholds in the lower frequencies (1, 2 kHz), mild elevation (< or =10 dB) in the midfrequencies (4, 8 kHz), and marked rise > or =>30 dB) in the ABR thresholds at higher frequencies (>16 kHz). Surprisingly, the single long-term animal showed recovery of hearing in midfrequencies and high frequencies with the passage of time. CONCLUSIONS: Cochleostomy and intracochlear infusion result in auditory insult limited largely to the region of surgical trauma. Demonstration of hearing preservation after surgical breach of the cochlea should encourage further development of potential diagnostic and therapeutic intervention into the inner ear.
Authors: Seiji B Shibata; Sarah R Cortez; James A Wiler; Donald L Swiderski; Yehoash Raphael Journal: Hum Gene Ther Date: 2012-02-08 Impact factor: 5.695
Authors: Zhiqiang Chen; Sharon G Kujawa; Michael J McKenna; Jason O Fiering; Mark J Mescher; Jeffrey T Borenstein; Erin E Leary Swan; William F Sewell Journal: J Control Release Date: 2005-11-07 Impact factor: 9.776
Authors: H Wang; R Murphy; D Taaffe; S Yin; L Xia; W W Hauswirth; M Bance; G S Robertson; J Wang Journal: Gene Ther Date: 2011-06-23 Impact factor: 5.250
Authors: David Lobo; Almudena Trinidad; José Ramón García-Berrocal; Jose María Verdaguer; Rafael Ramírez-Camacho Journal: Eur Arch Otorhinolaryngol Date: 2006-03-18 Impact factor: 2.503
Authors: Erin E Leary Swan; Mark J Mescher; William F Sewell; Sarah L Tao; Jeffrey T Borenstein Journal: Adv Drug Deliv Rev Date: 2008-09-21 Impact factor: 15.470