The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic pO(2) and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear.
The effect of blood flow promoting drugs, such as hydroxyethyl starch (HES) either of low or high molecular weight (HES 70, HES 200), pentoxifylline, ginkgo biloba, naftidrofuryl and betahistine, and various combinations of the drugs was studied in unexposed and noise-exposed (broad-band noise, bandwidth 1-12 kHz, 106 dB SPL, 30 min) guinea pigs. The results were compared without therapy and placebo (isotonic saline, NaCl). The cochlear blood flow (CoBF) and the partial pressure of oxygen in the perilymph (PL-pO(2)) were continuously and simultaneously recorded over a period of 210 min. In addition, cochlear microphonics (CMs), compound action potentials of the auditory nerve (CAPs) and auditory brain stem responses (ABRs) were registered. Noise-induced hearing loss (NIHL) paralleled a decrease of PL-pO(2). Both were found to occur before evidence of reduced CoBF. PL-pO(2) and CoBF declined progressively post-exposure, while CMs, CAPs and ABRs showed no further deterioration or signs of recovery up to 180 min after cessation of noise. Treatment started 60 min post-exposure, respectively after 90 min, without manipulation in unexposed animals, and was then studied for a further 120 min. In unexposed animals, CoBF increased significantly during infusion of HES 70, HES 200, pentoxifylline and betahistine. NaCl, ginkgo biloba and naftidrofuryl did not alter CoBF. PL-pO(2) decreased significantly during infusion of all administered drugs and combinations, except for NaCl. CMs, CAPs and ABRs remained constant, with the exception of increased ABRs after infusion of HES 70 and HES 200. In noise-exposed animals, a sustained therapeutic effect on cochlear ischemia was achieved only by HES 200 and pentoxifylline. HES 70, betahistine and ginkgo biloba compensated cochlear ischemia only during infusion; however, 30-60 min after termination of therapy, no significant difference of values for CoBF was observed compared to the untreated noise-exposed groups. NaCl and naftidrofuryl showed no effect on CoBF. None of the applied drugs had a sustained compensatory effect on cochlear hypoxia. CMs, CAPs and ABRs improved significantly after HES 70, HES 200 and betahistine, resulting in partial recovery of CMs, and partial (betahistine) or even full (HES 70 and HES 200) recovery of CAPs and ABRs. In contrast, NaCl, pentoxifylline, ginkgo biloba and naftidrofuryl had no therapeutic effect on NIHL.
Lamm
K
K
Department of Otolaryngology, Head and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, D-81675, Munich, Germany. k.lamm@lrz.tu-muenchen.de
Arnold
W
W
D000818:Animals; D001621:Betahistine / Q000494:pharmacology; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects*; D007758:Ear, Inner / Q000098:blood supply; D005260:Female; D020441:Ginkgo biloba; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000503:physiopathology; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007511:Ischemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009257:Nafronyl / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D010498:Perilymph / Q000187:drug effects* / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D014665:Vasodilator Agents / Q000494:pharmacology*
D006895:Hydroxyethyl Starch Derivatives; D010936:Plant Extracts; D014665:Vasodilator Agents; D009257:Nafronyl; D010100:Oxygen; D010431:Pentoxifylline; D001621:Betahistine