[The broncholytic effect of buffers applied by inhalation. A new pharmacological concept (author's transl)]. / Broncholytische Wirkung inhalativ applizierter Puffersubstanzen. Ein neues pharmakologisches Wirkingsprinzip.

A new method was developed by which the tone of bronchial smooth muscle can be measured breath by breath in man. Thereby state and reactions of bronchial smooth muscle can be studied. Former investigations had shown that carbonic anhydrase inhibitors have a broncholytic effect. The mechanism of action presumably is the prevention by carbonic anhydrase inhibitors of CO2 induced changes of pH within the bronchial epithelium occurring breath by breath with different partial pressures of CO2. Principally a stabilisation of pH can also be achieved by buffers. Therefore the broncholytic effect of buffers was tested and a 10% buffer solution of phosphat and Tris (THAM) buffer applied by inhalation in two healthy volunteers. In both cases a significant bronchodilation was seen, which in case of phosphate was substantially greater than in case of conventional broncholytics (e.g., fenoterol). As concerns onset and duration of the broncholytic effect, buffers are similar to conventional broncholytics. It is great advantage that buffers do not stimulate bronchial peristalsis and do not have cardiac side effects, contrary to conventional broncholytics.

[Two new characteristic quantities for characterization of the bronchial state in vivo and of pharmacological effects. The discordant behaviour of the bronchial system (author's transl)]. / Zwei neue Kenngrössen zur Charakterisierung des bronchialen Status in vivo und bronchial wirksamer Substanzen.

The classical quantity to characterize the state of the human bronchial system is the airway resistance (Raw). We have developed a new method for measuring the anatomical dead space (VD) and we have shown that the bronchial system may be characterized by the anatomical VD as well. Both Raw and VD are taken as mean values. In systematic investigations with our new VD method we found two facts: (1) under certain conditions VD depends unequivocally on the tidal volume (VT), the socalled VT gradient, and (2) VD varies periodically (bronchial peristalsis). The same is valid for Raw. From these observations one can derive two new characteristic quantities for the human bronchial system: (1) the standard deviation of the oscillations (sigma) as a measure of the bronchial motility and (2) the VT gradient as a measure of the bronchial compliance. With the aid of the two new characteristic quantities two types of bronchial reactions are defined: the concordant and the discordant reaction. Concordant means: VD increases (Raw decreases, respectively), sigma decreases, and the absolute value of the VT gradient increases or all effects are inverted. Discordant means: deviations from the concordant behaviour. All given examples but one show a discordant reaction. The new characteristic quantities improve the possibility to discriminate bronchial reactions, e.g., on drugs. The discordant behaviour is an expression for the complexity of the bronchial system.

[Dependence of the anatomical dead space on the tidal volume and on the endexpiratory lung volume: dynamic behaviour and stabilization of the bronchiolar tone (author's transl)]. / Die Abhängigkeit des anatomischen Totraumvolumens vom Atemzugvolumen und vom endexpiratorischen Lungenvolumen: Das dynamische Verhalten und die Stabilisation des Bronchialtonus.

The anatomical dead space was measured in dependence on the tidal volume and on the endexpiratory lung volume (respiratory level). A new method, the method of dead air plateau, was employed. The dead space increases with tidal volume (4 ml/100 ml). It is not dependent on the respiratory level. This was also directly shown in breathing manoeuvres changing the respiratory level rectangularly. In such manoeuvres a stabilization process can be seen. The same results give resistance measurements (oscillatory method). Values are taken in the endinspiratory state. This corresponds to the dead space volume. The 70% time of the stabilization reaction can be estimated, it is 20 sec. Taking this time into account, it is well understood that dead space volume is dependent on the tidal volume, but not dependent on the respiratory level. This time also makes evident that the often mentioned history of lung parameters lasts approximately 20 sec. The biological significance of the stabilization is discussed.

[The broncholytic effect of carboanhydrase inhibitors in subjects with healthy lungs (author's transl)]. / Die broncholytische Wirkung von Carboanhydrase-Hemmern bei Lungengesunden.

Carboanhydrase inhibitors are said to have a positive effect on respiratory insufficiency. We examined this, especially regarding the bronchial system. Actions and reactions of the human bronchial system can be followed by measurement of the anatomical dead space breath by breath. We have developed a new method which was tested by classical broncho-effective substances. Our experiments show in case of two men with healthy lungs that the three carboanhydrase inhibitors acetazolamide, methazolamide, and dichlorphenamide have a pronounced broncholytic effect. The effect is greater than that of fenoterol. In addition the bronchial peristalsis and the bronchial compliance are increased. In contrast to fenoterol carboanhydrase inhibitors have no cardiac side effect.

[Polarographic measurements of PO2 with a 95% response time of 7-10 msec (author's transl)]. / Polarographische Messungen des O2-Partialdruckes in der Gasphase mit einer 95%-Einstellzeit von 7-10 msec.

A fast PO2 tracing with 95% delay times of 15-20 msec in routine is necessary for measurement of the PO2 jumps in the expired air, particularly for the precise measurement of the so-called dead-air plateau. A Clark type PO2 electrode has been developed which has the demanded property. This electrode has four characteristic features: (1) a glasscoated Pt cathode with a tip diameter of 0.3 mm (diameter of the Pt wire = 0.1 mm); (2) a differential screwdrive for feeding the cathode 50 micrometer per turn; (3) a 0.2- to 0.3-micrometer-thin polytetrafluorethylene membrane, and (4) a special polishment of the surface of the cathode. The electrode has a 95% response time of 15-20 msec in routine when tracing PO2 changes from 150 to 750 mm Hg. About 30% of the prepared electrodes have response times of 7-10 msec. The output of the electrode in air is stable within the first 3 h (deviation smaller than 0.2%) and then decreases within 10 h approximately 1% per hour. The response times are constant for more than 48 h. The output of the electrode is linear from 0 to 760 mm Hg PO2. Within the accuracy of measurement the output is independent of PCO2.