In vivo assessment of droperidol-induced bronchial relaxation in dogs using a superfine fibreoptic bronchoscope

Abstract

Droperidol has been reported to cause bronchodilatation but its mechanism(s) of action is unknown. We have evaluated the spasmolytic effect of droperidol on histamine- and serotonin (5-HT)-induced bronchoconstriction in dogs. Bronchial cross-sectional area was assessed with a superfine fibreoptic bronchoscope. Twenty-eight mongrel dogs were allocated randomly to one of two groups (histamine and 5-HT) to receive either histamine or 5-HT to induce bronchoconstriction. Changes in bronchial cross-sectional area were presented as percentage of basal bronchial cross-sectional area. Continuous i.v. infusion of histamine 500 micrograms kg-1 h-1 or 5-HT 500 micrograms kg-1 h-1 decreased percentage bronchial cross-sectional area by 46.4 (14.3)% or 68.9 (13.7)%, respectively. In both groups, droperidol reversed bronchoconstriction in a dose-dependent manner. In the histamine but not in the 5-HT group, plasma adrenaline and noradrenaline concentrations increased significantly after i.v. droperidol. In addition, propranolol antagonized droperidol-induced relaxation in the histamine but not in the 5-HT group. Our data indicate that the spasmolytic effect of droperidol on canine airway was caused, at least in part, by both catecholamine releases and 5-HT receptor antagonism.

Droperidol Attenuates Contractile and Phosphatidylinositol Responses of Rat Trachea

“…Muscarinic receptor agonists activate the PI response through Gprotein-coupled phospholipase C and subsequently increase the Ca 2+ release from sarcoplasmic reticulum and the Ca 2+ influx from extracellular fluid [9]. Droperidol is lipid soluble and inhibits CCh-, 5-HT-, and histaminereceptor-agonist-induced airway smooth muscle contractions [2][3][4][5]. In addition, it has been suggested that AF stimulates G proteins [10,11] and produces IP 3 [12].…”

“…In animal experiments [2][3][4][5], droperidol attenuated airway smooth muscle contraction induced by serotonin (5-HT), histamine, and carbachol (CCh) [2][3][4][5]. However, the intracellular mechanisms involved in the droperidolinduced attenuation of airway smooth muscle contraction are not fully understood.…”

In vivo spasmolytic effect of ketamine and adrenaline on histamine‐induced airway constriction

“…However, Brown's method requires the use of very large equipment. Therefore, we have developed a portable direct method using a superfine fibreoptic bronchoscope to assess changes in bronchial calibre (13)(14)(15). We have found that the bronchoscopic method is more specific to assess airway calibre than indirect methods as, when assessing Yobronchial cross-sectional area (BCA) completely returned to prehistamine value by adrenaline administration, yet %dynamic pulmonary compliance (C+) and %airway resistance (Raw) did not (15).…”

“…However, recent studies indicated that the indirect measurements are not quite reliable (11,12). Thus, we developed a new direct method to assess airway calibre, which is based on the use of a superfine fibreoptic bronchoscope (13)(14)(15). We employed this method to evaluate the effect of ketamine on bronchoconstriction induced by histamine in dogs.…”

Editorial II

“…Each research group in this area has their own research technique. Brown's group 3 (Johns Hopkins University, USA) and Hirota's group 4 (Hirosaki University, Japan) are measuring rather distal airway diameter using highresolution computed tomography (CT) and super®ne ®breoptic bronchoscope techniques, respectively (Fig. 1A).…”