Continuous recording of intrapulmonary "compressed air" as a sensitive noninvasive method of measuring bronchial obstruction in guinea pigs

Abstract

The method presented is based on whole-body plethysmography. The apparatus consisted of two chambers (a = respiratory, b = body chamber) separated by a tight water-filled rubber cuff which was fixed around the head of the animal. Experiments were performed under constant gas conditions: temperature 30 degrees C, 100% relative humidity, the volumes of the two chamber being identical. Volume changes in the chamber (delta Va, delta Vb) were recorded continuously by means of pressure transducers. Respiratory flow was calculated by differentiation of delta Va with respect to time. The three parameters delta Va, delta Vb and respiratory flow allowed the calculation of breathing frequency, inspiration/expiration ratio, (peak) expiratory flow and specific airway conductance. In addition we describe a new parameter indicating bronchial obstruction: a graphical plot of delta Vb against delta Va produces a closed loop, the area of which reflects the degree of airway obstruction, and we read off the parameter we term "compressed air" from this graph. In our hands this parameter was more than ten times as sensitive as other measures of bronchial obstruction. Using this new technique we have carried out pharmacological studies with eicosatetraynoic acid (ETYA), 2-aminomethyl 4-t-butyl-6-iodophenol (MK 447 = radical scavenger), the histamine antagonist clemastine and the histamine antagonist cimetidine. In allergen-tested animals we observed mild protective effects of ETYA when given as an aerosol (3 mg) and pronounced effects of MK 447 (4 mg i.p.). Combined H1 H2-antagonism was much more effective in preventing allergen-induced bronchial obstruction than H1-antagonism alone.