Ganciclovir prophylaxis for cochlear pathophysiology during experimental guinea pig cytomegalovirus labyrinthitis.
The effectiveness of the antiviral agent ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) against guinea pig cytomegalovirus was tested in vitro in guinea pig embryonic fibroblasts and in vivo in an experimental guinea pig cytomegalovirus labyrinthitis model. In vitro, ganciclovir completely prevented guinea pig cytomegalovirus infection of guinea pig embryonic fibroblasts at concentrations above 32.6 micrograms/ml. In vivo, antibody-negative animals had an average 17-dB elevation in their auditory nerve compound action potential thresholds (P less than 0.01, t test) and showed signs bilaterally of guinea pig cytomegalovirus labyrinthitis 8 days after intrathecal inoculation of virus. Ganciclovir administration starting 1 day before inoculation prevented the development of both cochlear histopathologic change and hearing loss. Guinea pig cytomegalovirus meningitis was observed in both the drug-treated and untreated groups. High-pressure liquid chromatography confirmed the presence of ganciclovir in the serum, perilymph, and cerebrospinal fluid of the drug recipients. Prophylactic ganciclovir thus can protect the cochlea from the histopathologic changes and hearing loss normally associated with experimental guinea pig cytomegalovirus labyrinthitis.
Woolf
N K
NK
Department of Surgery, University of California San Diego Medical Center 92103.
Ochi
J W
JW
Silva
E J
EJ
Sharp
P A
PA
Harris
J P
JP
Richman
D D
DD
D000161:Acoustic Stimulation; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology*; D003586:Cytomegalovirus Infections / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir; D006168:Guinea Pigs; D007759:Labyrinth Diseases / Q000517:prevention & control*; D007762:Labyrinthitis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012684:Sensory Thresholds / Q000187:drug effects; D000159:Vestibulocochlear Nerve / Q000503:physiopathology
D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir