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EFFECT OF ALMITRINE BISMESYLATE ON BREATHING PATTERN DURING HYPOXIA/HYPERCAPNIA IN RATS AND FERRETS
Author(s) -
Austin C. A.,
Wach R. A.,
Bee D.,
Finlay M.,
Emery C. J.,
Suggett A. J.,
Barer G. R.
Publication year - 1987
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1987.tb02420.x
Subject(s) - hypercapnia , plethysmograph , ventilation (architecture) , medicine , tidal volume , hypoxia (environmental) , anesthesia , dead space , respiratory minute volume , functional residual capacity , control of respiration , respiratory system , lung , lung volumes , chemistry , oxygen , mechanical engineering , organic chemistry , engineering
SUMMARY 1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead‐space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied. 2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (V E ) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine. 3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in V E . Slow infusions of almitrine caused a further increase in V E usually via an increase in tidal volume (V T ) but not frequency (f). 4. In two series of rats ( n = 9; n = 6) severe and moderate degrees of tracheal obstruction caused a fall in P aO 2 and a rise in P aCO 2 , a fall in V E due to both V T and f and large changes in oesophageal pressure ( P oes ), which often became positive on expiration. Almitrine infusions usually caused a rise in P aO 2 , a rise in V T and no change in f; with moderate obstruction, P oes also rose. The results were thought to depend on the balance between improved ventilation and increased O 2 demand of the respiratory muscles. 5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead‐space to the trachea. A slow infusion of almitrine caused a significant rise in P aO 2 before any significant change in V E was detected; P aCO 2 fell at some time during the infusion, but not significantly. The initial significant rise in P aO 2 , at 2.5 min, was not associated with significant changes in T I (time of inspiration) and V T /T I . At 5 min V T /T I , T I and P aO 2 were all significantly altered. 6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total V E . Possible conclusions with respect to the action of almitrine in patients with COAD are discussed.