Labyrinthine barriers and cochlear homeostasis.

The blood-labyrinth barrier is a concept used to explain the stability of composition of the labyrinthine fluids in spite of systemic alterations in blood composition. This blood-labyrinth barrier concept was tested by injecting various test substances into the systemic circulation of experimental animals and recovering these compounds in perilymph. The concentration of each test substance in perilymph lagged behind that of serum, and the transport of a series of test substances was found to be inversely related to the molecular weight and diameter. Among the osmotic agents injected, glycerol and urea penetrated into perilymph to a considerable degree, however, mannitol did not enter perilymph in any significant amount. This may explain the clinical differences noted with these agents in testing for Meniere's disease. Furosemide, an ototoxic diuretic, was found to penetrate into perilymph after intravenous injection into chinchillas. The concentration of furosemide, measured by high pressure liquid chromatography, was fairly constant at the time of full recovery of endocochlear potential after doses of 50-200 mg/kg. The principle of correlating drug concentration in serum and in inner ear fluids with pathophysiologic effect may provide a prediction of threshold concentration of ototoxic effect by measurement of serum concentration of the drug. More extensive studies are necessary to clarify the role of the blood-labyrinth barrier in the regulatory mechanisms which maintain the homeostasis in the inner ear and the pathology which may follow when this homeostasis is disrupted.