Search

The authors study the changes in cardiopulmonary function after application of bromhexine metabolite VIII (NA 872) in an animal model of adult respiratory distress syndrome (ARDS) and bromhexine glucose solution (BGS) in ARDS patients. After damage of the lung alveolar surfactant by intratracheal atomization of 0.2 M HCl in LEWE Minipigs significant changes in lung compliance, dead space ventilation, venous admixture, alveolo-arterial oxygen tension difference, pulmonary vascular resistance, and oxygen uptake are present under application of NA 872 in comparison to untreated animals. In ARDS patients treated with BGS, pulmonary function is significantly ameliorated indicated by changes in static effective compliance, oxygen exchange ratio, and alveolo-arterial oxygen tension difference.

The effect of ambroxol and bromhexine on the yeast cell wall- and arachidonic acid (AA)-induced luminol-respectively lucigenin-dependent chemiluminescence (CL) of alveolar macrophages (AM) of patients with lung diseases has been investigated. Both drugs cause a suppression of the induced CL. These results suggest that ambroxol and bromhexine reduce the generation of reactive oxygen metabolites (ROM) by AM. The mechanism of action is thought to involve the activation of the acyl-CoA: lysophosphatide acyltransferase. The increase of this enzyme activity lowers probably the intracellular concentration of free AA and consequently also the production of ROM. The investigations show a new possibility for the influence of biosynthesis of ROM and likely of eicosanoids, which play an important role as pathogenetic mediators in different lung diseases.

The action of ambroxol was tested in an in vivo guinea pig asthma model. Ambroxol, a compound with antiallergic properties effects the mediator releasing cells in vitro and surfactant secretion from alveolar type II cells. This paper deals with the action of ambroxol in an in vivo asthma model in guinea pigs. Ovalbumin sensitized guinea pigs were artificially ventilated by negative chest wall pressure, using a tank respirator. Breathing parameters were measured pneumotachographically. The experimental animals were treated with 50 mg/kg ambroxol i.p. for 5 days; control animals received saline only. The results indicate that pretreatment with ambroxol had no significant effect on the allergic bronchial constriction, while in vitro ambroxol effects on mediator releasing cells and surfactant production point to antiallergic properties. An explanation of the failure of allergenic preventing effects of ambroxol in vivo may be its insufficient concentration in the tissue.

The increased generation of reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, X OH, OX-) by alveolar macrophages (AM) and neutrophils has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. With regard to a possible therapeutic application in this context the effect of bromhexine and ambroxol on the activity of AM of of guinea-pigs and of patients with lung diseases was investigated. The activity of AM, which were isolated by bronchoalveolar lavage, was determined by means of chemiluminescence (CL)-measuring. Ambroxol and bromhexine cause a depression of the spontaneous as well as of the induced CL [yeast cell walls, yeast glucan, exogenous arachidonic acid (AA)] of AM. AM from guinea-pigs and in some cases also from patients show primarily an increase of the CL-signal under the influence of bromhexine. These results suggest that ambroxol and bromhexine reduce the production of ROM by AM. The mechanism is possibly due to the activation of acyl-CoA-lysophosphatide acyltransferase. The increase of this enzyme activity lowers the intracellular concentration of the free AA, whereby the generation of ROM is diminished too. The investigations exhibit a new possibility of influence of respiratory burst and thus indirectly of AA-liberation from phospholipids. The probable reduction of AA-liberation by these drugs could also be of importance for other lung cells especially concerning the biosynthesis of eicosanoids (AA-metabolites), which play an important part as pathogenetic mediators in different lung diseases.