Ikuo Ise

Effect of ethacrynic acid, furosemide, and ouabain upon the endolymphatic potential and upon high energy phosphates of the stria vascularis.

The loop diuretics ethacrynic acid (EA) and furosemide (FU) were applied systemically to guinea pigs at dosages from 10–100 mg/kg. At high dosages the endolymphatic potential (EP) invariably turned negative. When the EP had reached maximum negative values due to EA, the ATP levels of the stria vascularis were moderately reduced, but P‐creatine levels were normal. In the case of FU both high energy phosphates remained at normal levels. When EA and FU intoxicated ears were subjected to ischemia, the rate of decline of ATP and P‐creatine was markedly less than the ischemic decline in nonintoxicated ears. These results suggest a strong interference with energy utilization, and in the case of EA a moderate impairment of energy generation. In severe intoxication by perilymphatically applied ouabain (10−3 M) strial ATP remained normal but P‐creatine was significantly increased. The reduction of the ischemic decline rate in ouabain intoxicated ears was even more marked than in the case of EA or FU, indicating a very strong interference with energy utilization, presumably due to complete inhibition of Na+K+‐ATPase. The I50 of the endolymphatic potential with regard to perilymphatically applied EA and FU was found to be 10−5 M and 2 x 10−4 M respectively. By K contrast, strial Na+K+‐ATPase was 50% inhibited with 5 x 10−3 M EA and not inhibited at all by FU. It is therefore unlikely that the effect of loop diuretics upon the endolymphatic potential is due to interference with strial Na+K+‐ATPase.

Bone destruction due to the rupture of a cholesteatoma sac. A pathogenesis of bone destruction in aural cholesteatoma

Severe bone destruction in a cholesteatoma is one of the characteristic clinical features. To clarify the mechanism of bone destruction in cholesteatoma, the matrix of cholesteatoma and the attached bone, obtained during middle ear surgery, was observed by light microscope. Rupture of the epithelial lining in a cholesteatoma and the escaping contents (keratin), which gave rise to intense characteristic granulations in subepithelial tissue, were found. Furthermore bone destruction was always found at the site of subepithelial tissue of cholesteatoma. From these facts, the escape of contents from the sac of cholesteatoma into the subepithelial layer is considered to be an important factor in the mechanism of bone destruction.

Effect of iodoacetic acid upon cochlear potentials

Lotz et al. reported that perilymphatic application of 5 X 10(-3) M iodoacetic acid (IAA) in the guinea pig does not influence the first-order cochlear microphonics (CM1) under aerobic conditions. However, in ischemia the rate of decline of the second-order microphonics (CM II, also called postmortem CM) was significantly increased by IAA. The authors concluded that glycolysis plays no role in maintaining the CMI, but that it is responsible for supporting the CMII. In carefully controlled experiments we found that in the respiring guinea pig, perilymphatic application of 5 X 10(-3) M IAA produced a rapid and pronounced effect upon both the endolymphatic potential and the CM. In particular, the CM dropped to less than 0.5% of its initial level within 40 min, due to IAA, whereas it took 120 min to drop to the same level in total ischemia (without IAA). We therefore reject the above-mentioned proposition that IAA is ineffective upon cochlear potentials under aerobic conditions; moreover, we find that even under aerobic conditions, the CM drops well below the usual CM II level substantially faster than under anaerobic conditions (without IAA). Other important findings, including an anoxia-sensitive negative component of the endolymphatic potential due to severe intoxication with IAA, and the effects of pretreatment of the organ of Corti with low concentrations of IAA upon the CM II are discussed.