In vivo spasmolytic effect of ketamine and adrenaline on histamine-induced airway constriction. Direct visualization method with a superfine fibreoptic bronchoscope.

Abstract

Ketamine (K) has been reported to produce bronchodilation in patients suffering from asthma. Although most researchers have used indirect measurements to study the effect of K in vivo, the reliability of these indirect methods are controversial. We have developed a new technique to measure the bronchial cross-sectional area (BCA) in vivo with a superfine fibreoptic bronchoscope (SFB). Employing this method, we evaluated in vivo spasmolytic effect of K and adrenaline (A). Twenty-one mongrel dogs were anaesthetized with pentobarbitone (30 mg.kg-1) and paralyzed with pancuronium (200 micrograms.kg-1.h-1). The trachea was intubated with an endotracheal tube that has a second lumen for insertion of a SFB (OD: 2.2 mm) to measure the BCA continuously. The tip of the SFB was placed between the 2nd and 3rd bronchial bifurcation of the right lung. A videoprinter printed the BCA, which was then measured with NIH Image. Bronchoconstriction was produced with histamine (H: 10 micrograms.kg-1 + 500 micrograms.kg-1.h-1) which was administered until the end of the experiment. The BCA was assessed before and 30 min after the start of H infusion. The dogs were randomly allocated to 3 groups of 7 dogs each. In group K, K (0-10 mg.kg-1) was given i.v., and the BCA was measured 5 min after each K dose. In group A, A (0-0.4 microgram.kg-1) was given i.v., and the BCA was measured 1 min after each A dose. In group A + K, K (1 mg.kg-1 i.v. + 1 mg.kg-1.h-1 i.v.) was given followed, 30 min after, by A i.v. in the same doses as in group A. The BCA was assessed 30 min after the start of K and again 1 min after each A dose. K 10 mg.kg-1 reversed H-induced bronchoconstriction. A subthreshold dose of K significantly potentiated the effect of A, reversing the decrease in BCA by H. We have found that K could reverse the H-induced bronchoconstriction and potentiate the A-induced bronchial relaxation.