Low Dose Betahistine in Combination With Selegiline Increases Cochlear Blood Flow in Guinea Pigs

Abstract

Objective: Betahistine is frequently used in the pharmacotherapy for Menière's Disease (MD). Little is known about its mode of action and prescribed dosages vary. While betahistine had an increasing effect on cochlear microcirculation in earlier studies, low dose betahistine of 0.01 mg/kg bw or less was not able to effect this. Selegiline inhibits monoaminooxidase B and therefore potentially the breakdown of betahistine. The goal of this study was to examine whether the addition of selegiline to low dose betahistine leads to increased cochlear blood flow.

Methods: Twelve Dunkin-Hartley guinea pigs were anesthetized, the cochlea was exposed and a window opened to the stria vascularis. Blood plasma was visualized by injecting fluoresceinisothiocyanate-dextrane and vessel diameter and erythrocyte velocity were evaluated over 20 minutes. One group received low dose betahistine (0.01 mg/kg bw) and selegiline (1 mg/kg bw) i.v. while the other group received only selegiline (1 mg/kg bw) and saline (0.9% NaCl) as placebo i.v.

Results: Cochlear microcirculation increased significantly (P < .001) in guinea pigs treated with low dose betahistine combined with selegiline by up to 58.3 ± 38.7% above baseline over a period of up to 11 minutes. In one guinea pig, the increase was 104.6%. Treatment with Selegiline alone did not affect microcirculation significantly.

Conclusions: Low dose betahistine increased cochlear microcirculation significantly when combined with selegiline. This should be investigated in further studies regarding dose-effect relation in comparison to betahistine alone. Side effects, in particular regarding circulation, should be considered carefully in view of the clinical applicability of a combination therapy in patients with MD.

Keywords: Menière’s disease; betahistine; cochlea; guinea pig; microcirculation; selegiline.

Figure 1.

Betahistine effect on cochlear microcirculation by Ihler et al: Betahistine (0.01 mg/kg bw) alone was not able to increase cochlear blood flow significantly. Image extracted from Ihler et al.

Figure 2.

Cochlear fenestration: Image (A) shows the protruding left cochlea of a guinea pig into the tympanic cavity (3.2× magnification) before the outer vessels are removed with a microsponge (lateral view). The rectangle indicates the window which is carved into the outer bony layer of the cochlea wall. The second turn of the cochlea is marked by broken lines. Image (B) outlines the area of fenestration. The cochlea is innervated by the cochlear nerve (1), whose fibers run in between the scala media (2) and scala tympani (3) along the basilar membrane (4) to the organ of Corti (5) with inner and outer hair cells and the tectorial membrane. Between the scala vestibuli (6) and the scala media is Reissner’s membrane (7). The stria vascularis (8) lateral to the scala media is accessed by carefully removing the upper bony layer of the cochlear wall.

Figure 3.

Cochlear blood flow after baseline recordings in absolute values in individual animals from the groups B + S (black lines, n = 6, treatment) and S + S (gray lines, n = 5, control). While most animals treated in B + S showed a marked increase in cochlear blood flow, values in the whole S + S group stayed within a small range.

Figure 4.

Relative change of cochlear blood flow after baseline recordings on average in both groups. Mean values ± standard deviation. Brackets: significant difference at respective timepoints between groups, level of significance denoted by asterisk (** = P < .01, * = P < .05). Group B + S (black diamonds, treatment, n = 6) showed a significant increase in cochlear blood flow compared to group S + S (white diamonds, control, n = 5).