Thorax: first published as 10.1136/thx.21.4.333 on 1 July 1966. Downloaded from
Thorax (1966), 21, 333.
Effect of norepinephrine and isoprenaline on the airway resistance of patients with chronic bronchial obstruction
NO1 ZAMEL, EDUARDO Z. FARACO, AND FLAVIO M. DE FREITAS From the Cardio-pulmonary Laboratory, Department of Clinical Therapeutics, Porto A legre Medical School, Untiversity of Rio Grantde do Sul, Brazil
The combination of isoprenaline with phenyl- calcified foci in the right upper lobe. In both, symptoms ephrine was recently suggested to have a more of chronic bronchitis had preceded the onset of pul- marked bronchodilator action in patients with monary tuberculosis. bronchial obstruction than isoprenaline alone. This None of the patients had received corticosteroids for to a period of at least 30 days before the test, and none increased action has been attributed the vaso- had received bronchodilators for at least 24 hours. A constrictive properties of phenylephrine, which Vaponefrin nebulizerl connected to a regulating flow may cause mucosal decongestion. The addition of valve of an air cylinder was used for the administration this effect to the bronchial muscle relaxation of the aerosols. The valve was set to deliver a flow of elicited by isoprenaline would allow a greater 6 1./minute. All patients were exposed to doses of increase of the internal diameter of the bronchi 10 mg. isoprenaline (5 mg./ml.) and 2 mg. norepin- (Cohen, 1962; Kallos and Kallos-Deffner, 1964; ephrine (1 mg./ml.). Each exposure lasted approxi-
Cohen and Hale, 1965). mately 10 minutes. The airway resistance and thoracic http://thorax.bmj.com/ Since is one of the most power- gas volume were measured by means of a 600-1. body norepinephrine plethysmograph by the method of DuBois, Botelho, ful vasoconstrictive substances presently available, and Comroe (1956). The loops were recorded by a the appraisal of its value as a bronchodilator cathode-ray photographic recording system2. At least would have both physiopathological and thera- six loops were selected to obtain the mean value of peutic implications. There are no references in the each determination. The patients panted at a frequency medical literature to the use of aerosols contain- of approximately 2 cycles/second and the airway ing norepinephrine. This study was therefore resistance was measured at flow rates of 0-5 l./second. undertaken in order to evaluate the effects of A control measurement was obtained in every norepinephrine before and after the administra- patient. Then one of the drugs was administered, and on September 24, 2021 by guest. Protected copyright. on the resistance of the determination of the airway resistance and thoracic tion of isoprenaline airway gas volume was repeated. As soon as a convenient patients with chronic bronchial obstruction. number of loops had been photographed, the second drug was given and a third determination was carried MATERIAL AND METHODS out. Since a random order in the administration of the drugs had been observed on the first day, the same Twenty patients (16 male and four female) aged 11 to procedure was repeated the following day, but the 66 years (average age 44 years) were studied. Ten drugs were used in reverse order. patients were diagnosed as having chronic bronchitis An interval of approximately five minutes was and 10 as having asthma, according to the criteria allowed to elapse between the end of each exposure of defined by the Ciba Guest Symposium (1959). The the patient to the aerosol and the beginning of the diagnosis of gross widespread pulmonary emphysema determination of the airway resistance and thoracic was made in five patients with chronic bronchitis and gas volume. Meanwhile the patient had been sitting in five with asthma. This diagnosis was based on the inside the body plethysmograph in order to achieve an radiographic examination of the lungs and in accor- appropriate warming up of the air in the box and its dance with the criteria of Simon and Galbraith (1953). sufficient saturation with water vapour. The same was One patient with a long history of chronic bronchitis done before the control measurement. Each complete had recently developed clinical and radiological signs suggesting bronchiectasis. Two patients had had pul- 'The Vaponefrin Co. Dist., Edison, New Jersey, U.S.A. monary tuberculosis; one had radiological signs of 2DR-8 Research Recorder, Electronics for Medicine Inc., White fibrous scarring in both upper lobes and the other had Plains, New York, U.S.A. 333 2D Thorax: first published as 10.1136/thx.21.4.333 on 1 July 1966. Downloaded from
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< 2 ON-2 U Cont'rol z FIG. 1. Behaviour of airway I I 2 4 6 8 10 2 4 6 After norepinephrine Atter isoprenoline AIRWAY RESISTANCE (cm.H20/1i./sec.) 10 http://thorax.bmj.com/ V .Cc cL cA. 6... ^_co _, on September 24, 2021 by guest. Protected copyright. -i 0 U) FIG. 2. Behaviour of thoracic 4( I C- gas volume during control and 13 test periods (see text). 4 X c 0. 0 0 .5 .5 8 10 2 4 e le After isoprenoline THORACIC GAS VOLUME (I.) Thorax: first published as 10.1136/thx.21.4.333 on 1 July 1966. Downloaded from Effect of norepinephrine and isoprenaline on the airway resistance of patients 335 determination of airway resistance and thoracic gas not significant when isoprenaline was used after volume consumed an additional five-minute period. norepinephrine (Table I, Fig. 2B). Student's t-test was used in the statistical analysis. The data obtained were arranged according to the 'paired technique', since each patient served as his own DISCUSSION control. RESULTS The relation between airway resistance and thoracic gas volume has been well established; Results for airway resistance and thoracic gas the airway resistance decreases when the lung volume are summarized in Table I and arranged volume increases (Briscoe and DuBois, 1958). It graphically in Figures 1 and 2. was also demonstrated by Butler, Caro, Alcala, and DuBois (1960) that this relationship is deter- TABLE I mined by the elastic properties of the lung. These EFFECTS OF NOREPINEPHRINE AND ISOPRENALINE ON authors found that, in patients with asthma and in AIRWAY RESISTANCE AND THORACIC GAS VOLUME patients with pulmonary emphysema, the change in airway resistance per unit change in lung Mean Mean Period of Study M±SaD±SD. Difference P volume was less than normal. They also found ±S.E.M. that the curve of airway resistance versus lung Airway Resistance (cm. H50' 1. sec.) volume could be altered in normal subjects, in Control .. 450±170 After 1 47±029 <0 001 patients with asthma, and in patients with pul- norepinephrine 3 03±1 17 Plus 0 67±0 14 <0 001 monary emphysema by the administration of isoprenaline.. 2-36±0-78 bronchodilator agents without any evidence of an Control . 4-12±157 increase in lung elastic pressure. Therefore the After 1-88 ±0-32 <0-001 isoprenaline.. 2-24±0 70 relation of airway resistance to lung volume is Plus 0-06±0-09 Not significant conditioned by the distensibility of the lung tissue norepinephrine 2-30±0 80 and of the airway walls, and the correction of Thoracic Gas Volume (1.) airway resistance measurements for lung volume Control .. 5 24±2 22 After 0-41±0-22 Not significant changes is not possible if these factors are not norepinephrine 4-83±1i84 considered. http://thorax.bmj.com/ Plus 0-20- 0-14 Not significant isoprenaline .. 4-63 ±1t98 In the present series, the fall in airway resis- Control .. 493±2-03 tance after the administration of norepinephrine After 0-43±0-16 <0-02 and isoprenaline was not dependent on changes in isoprenaline .. 450±1-65 Plus 0 05±0 08 Not significant the thoracic gas volume, since this variable did norepinephrine 4-45 ± 1-65 not increase. Thus it may be postulated that the decrease in the airway resistance was occasioned AIRWAY RESISTANCE When norepinephrine was by an active increase of the bronchial lumen due used in the first place, there was a significant to the action of the drugs. on September 24, 2021 by guest. Protected copyright. decrease (P<0 001) of the airway resistance in The results of this study indicate that norepi- comparison with the control values (Table I, Fig. nephrine is an efficient bronchodilator agent. Its IA). The same occurred (P<0 001) with isopren- effects are proobably due to its vasoconstrictive aline (Table I, Fig. IC). Results for airway resis- properties, which can diminish the mucosal con- tance obtained when norepinephrine was admin- gestion component of bronchial obstruction. In istered after isoprenaline were not significantly the doses used, norepinephrine did not elicit a different from those obtained with isoprenaline further increase of the bronchial lumen when alone (Table I, Fig. ID). However, when this last administered after isoprenaline. Moreover, iso- drug was given after norepinephrine there was a prenaline caused an additional fall of the airway further significant decrease (P<0 001) of the air- resistance when given after norepinephrine. Since way resistance (Table I, Fig. IB). the average results for airway resistance and thoracic gas volume were about the same after THORACIC GAS VOLUME The administration of the cumulative use of both drugs (Table I), what- norepinephrine either before or after isoprenaline ever the order of their administration, it can be did not change appreciably the thoracic gas concluded that the limit of drop of airway resis- volume (Table I, Figs 2A and 2D). A slight but tance was determined by isoprenaline. A possible significant decrease (P<002) of the thoracic gas explanation for this observation could be the volume was noted when isoprenaline was used as stretching of the mucosa occasioned by the the first drug (Table I, Fig. 2C). Changes were muscular relaxation and consequent bronchiali Thorax: first published as 10.1136/thx.21.4.333 on 1 July 1966. Downloaded from 336 Noe Zamel and others dilatation induced by isoprenaline, which would REFERENCES minimize the importance of the component of Briscoe, W. A., and DuBois, A. B. (1958). The relationship between mucosal congestion. airway resistance, airway conductance and lung volume in sub- jects of different age and body size. J. clin. Invest., 37, 1279. Butler, J., Caro, C. G., Alcala, R., and DuBois, A. B. (1960). Physio- SUMMARY logical factors affecting airway resistance in normal subjects and in patients with obstructive respiratory disease. Ibid., 39, 584. Ciba Guest Symposium (1959). Terminology, definitions, and classifi- Twenty patients with long-standing bronchial cation of chronic pulmonary emphysema and related conditions. obstruction were exposed to aerosols of norepi- Thorax, 14, 286. Cohen, A. A., and Hale, F. C. (1965). Comparative effects of isopro- nephrine and isoprenaline, used in alternate terenol aerosols on airway resistance in obstructive pulmonary sequence. Both drugs elicited a significant decrease diseases. Amer. J. med. Sci., 249, 309. Cohen, B. M. (1962). Ventilatory responses to aerosols ofisoproterenol of the airway resistance. The results for airway and isoproterenol-phenylephrine. Curr. ther. Res., 4, 601. resistance obtained when norepinephrine was DuBois, A. B., Botelho, S. Y., and Comroe, J. H., Jr. (1956). A new method for measuring airway resistance in man using a body administered after isoprenaline were not signi- plethysmograph: values in normal subjects and in patients with ficantly different from those obtained with respiratory disease. J. clin. Invest., 35, 327. Kall6s, P., and Kall6s-Deffner, L. (1964). Comparison of the protec- isoprenaline alone. Isoprenaline caused an addi- tive effect of isoproterenol with isoproterenol-phenylephrine tional fall of the airway resistance when given aerosols in asthmatics. Int. Arch. Allergy, 24, 17. Simon, G., and Galbraith, H. J. B. (1953). Radiology of chronic after norepinephrine. bronchitis. Lancet, 2, 850. http://thorax.bmj.com/ on September 24, 2021 by guest. Protected copyright.