Antenatal Ambroxol Effects on Surfactant Pool Size and Postnatal Lung Function in Preterm Ventilated Rabbits

Abstract

Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool sizes were measured. One half of the ambroxol treated and control rabbits were given surfactant at delivery. Although surfactant improved lung function comparably for control and ambroxol treated rabbits, ambroxol treatments did not change ventilatory pressure requirements, compliances, or the recovery of intravascular labeled albumin in the lungs. Ambroxol treatments tended to increase lung volumes as evaluated by pressure-volume curves. The ambroxol treatments significantly increased lung tissue SatPC by 22 %, but there were no changes in alveolar SatPC pool values. These results do not indicate a large effect of ambroxol on lung function in preterm rabbits.

Changes in pulmonary function in preterm infants recovering from RDS following early treatment with ambroxol: Results of a randomized trial

“…There were no significant improvements in lung mechanics as evaluated by static pressure-volume curves and only a trend toward increased lung volumes. 7 In our clinical trial, ambroxol was given postnatally to newborns with established RDS, and we found a modest (but significant) improvement in lung mechanics immediately after extubation. The therapeutic benefits of ambroxol treatment on lung mechanics were not of the same magnitude as the effects achieved by surfactant replacement.…”

“…Up to now the effects of ambroxol on lung development in newborns with RDS are unknown in detail. Investigations by Sun et al 7 in preterm rabbits did not show a large effect of prenatal ambroxol treatment on lung maturation. In the ambroxol group, they found a modest increase in the lung tissue pool that is saturated with phosphatidylcholine.…”

“…5 + 0.5 ͱ1+ 2 и t L и VЈ A 4 и V D ). (7) These two formulas show that f* and V T * depend only on three parameters: pulmonary time constant (t L ), alveolar ventilation (VЈ A ), and dead space (V D ). Using this model, the effect of changes in the lung mechanics on the respiratory pattern can be approximated.…”

“…Numerous studies have demonstrated the efficacy of surfactant replacement therapy in RDS, [2][3][4][5] but only a few studies have tested the clinical efficacy of drugs that stimulate the synthesis or release of endogenous surfactant. [6][7][8] Previous studies on fetal animals 9 have shown that ambroxol (ambroxolhydrochlorid:trans-4-[(2-amino-3,5dibrom-benzyl)amino]cyclohexanol; Mucosolvan®, Thomae GmbH, Biberach a.R., Germany) improves the biosynthesis and secretion of surfactant by alveolar type II cells. Furthermore, ambroxol is concentrated in the lung tissue and may also have antioxidative and antiinflammatory properties.…”

Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?

“…In multiple trials, the early work by Liggins and Howie [82] has now been confirmed many times [7,11,45,63] proving that these reduce the frequency of respiratory distress syndrome, neonatal morbidity, and mortality in preterm gestation [17,32,82,113,135] . There has been ongoing discussion about the dose and type of steroid, the treatment interval, and whether repeat doses of GC are beneficial [20,22,36,58,59,65,87,105,136,152] .…”