Antitussive effect of the inhibition of carbonic anhydrase

Abstract

In a preceding work (12) the authors have demostrated that breathing in CO2 supressed cough when light and brief coughing excitations are used. With relatively strong excitation, although the complete supression of cough is not reached, a more or less manifest dimminution is indubitable. The results of this work demonstrated that CO2 effect is a change of the muscular expiratory activity: expiration lost its rough and in a certain form convulsive feature that is peculiar to cough. On the neumotacogram during cough access show the followmg results: under CO2 the maximal expiration speed is not so high, and its elevation is gradual at the beginning of expiration. Initial aceleration of expiratory flow in CO2 cough is lower than on the control. On CO2 cough not only strenght of ex­ piratory muscular contraction decrease, but contraction does not appear so sharp also. It is possible to say that on control cough expiratory contraction show convulsive feature that has dissappear in CO2 cough. Relative lenght of respiratory cycle phases on CO2 cough, comparatively to control cough values, is another demostrative fact of exposed interpretation. Is typical of cough the increase of inspiration expiration time ratio, and it is evident the contrast of lengthening of inspiratory phase to fastness of expiratory phase. During CO2 respiration, this Iíndex decrease in relation to control cough and decreases with relation to respiratory movements of animal quiet respiration.

Effect of CO2 respiration over glottis is quite characteristic. Glottis expiratory constriction decreases shortly after inhalation beging and soon the rhytmic oscilation of resistance characte­ ristic of normal expiration disappear. Glottis relax represents a manifestation of CO2 action that appears precociously to the antitussive effect.

Antitussive effect of carbonic anhydrase inhibitors is studied in the present work. Investigations are carried out on unanesthetized dogs. Graphics: pleural pressure, neumotachogram, arterial pressure in the femoral and glottis resistance. Cough is produced by tracheal excitation.

Acetazolamide intravenous produce a characteristic change of respiratory movements. Initially, tidal volume, respiratory rate and minute volume iucreascs. And this effect begins sometimes before injection is finished, After this short phase, a slowness of respiratory rate, tidal volume decrease comparatively to initial effect (but always greater than control), and minute volu­ me decrease comparatively to control respiration, are observed. After about 10 minutes, respiratory rate increases but slower being this rate than control breathing rate. Tidal volume also, along with volume minute, increases comparatively to the con­trol. After initial phase muscular expiratory activity decreases which is noted by expiratory pleural pressure (fig. 1).

Figure 2 shows mean values of tidal volume — obtain from neumotachogram integration — and minute volume, the control valúes being of quiet respiration the unit.

Antitussive effect-. In all experiences cough decreased by acetazolamide. The effect is like the one which the authors have found out before with CO2, but more evident. The expiratory phase of fit of coughing-also CO2 effect-become less convulsive, untill expiratory effort disappear.

The oscillations of resistance of the glottis dimminish or disappear completely by the acetazolamide, as well as below the effect of the respiration of CO2.

The injection of acetazolamide produces an immediate hypotension arterial almost always quite marked with bradycardia, but the pressure become normal much before the effect in the respiratory movements.

By injection of intracisternal acetazolamide, like antitussive effect, is produced.