Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (FDC) (5:5), was investigated on the cholinergic contractile tone induced by the parasympathetic activation of equine isolated airways. The drug interaction was analysed by using the Bliss Independence and Unified Theory models. Both tiotropium and olodaterol induced a sub-maximal concentration-dependent inhibition of bronchial contractility (E: tiotropium 83.6 ± 14.8%, olodaterol 76.9 ± 17.9%; pEC: tiotropium 8.2 ± 0.5; olodaterol 8.3 ± 0.6). When administered at 5:5 concentration-ratio, tiotropium plus olodaterol completely inhibited the bronchial contractility (E 102.7 ± 8.4%; pEC 9.0 ± 0.7). Strong synergistic interaction was detected for tiotropium/olodaterol combination (combination index 0.011). When administered at low concentrations, the drug mixture elicited up to 94.6 ± 9.5% effect that was 36.0 ± 8.1% greater than the expected additive effect. The results of this study demonstrate that the co-administration of tiotropium plus olodaterol at 5:5 concentration-ratio leads to synergistic inhibition of equine bronchial contractility when compared with either drug administered alone. These findings suggest that the currently available LABA/LABA FDC may be effective in delivering tiotropium/olodaterol combination at equipotency concentrations of each monocomponent into the lung and, thus, inducing synergistic effect in the airways.
Objective. The aim of the study was to determinate whether maternal position during the non-stress test (NST) in different weeks of pregnancy influences fetal heart rate patterns. Materials and methods. A total of 1055 NST lasting 30 min were performed in 368 autochthonous mothers with low-risk pregnancies. On the basis of maternal position during the test we divided into three groups: reclining, sitting, and walking. The cardiotocographic parameters considered were: number of minutes of reactive NST with minimum length, number of fetal movements, fetal heart rate baseline, number of large accelerations, number of dubious NST, and number of variable decelerations. Results. Fetal heart rate patterns in low-risk pregnancies were studied using NST in different gestational ages and in different maternal positions. Differences in heart rate were found in relationship to both gestational age and maternal position. The minimum length of NST necessary to record at least three large accelerations was significantly different in relationship to both gestational age and maternal position. The number of fetal movements perceived by the mother was greater in the reclining position than in sitting or walking. Together with the progression of pregnancy, the number of dubious NST decreased in all subgroups, especially in the sitting position. The greatest number of variable decelerations was observed in the reclining position and it was increased with pregnancy progression. The NST duration did not vary greatly in the reclining position, but in the sitting position or during walking, the time taken to record the three large accelerations required to define the trace as reactive, decreased significantly with the progression of pregnancy Conclusions. Non-stress test in sitting position or during walking should be encouraged because fetal reactivity is more quickly observed.
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