Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2004
Randomized Controlled Trial Clinical TrialRelationship between neutrophil elastase and acute lung injury in humans.
We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. ⋯ VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans.
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Pulm Pharmacol Ther · Jan 2004
Comparative StudyComparative effects of dopamine and dobutamine on hypercapnic depression of diaphragmatic contractility in dogs.
The present study was undertaken to evaluate the effects of dopamine and dobutamine on diaphragmatic contractility in dogs with induced hypercapnia. Animals were divided into three groups of ten each. In each group, hypercapnia (80-90 mmHg) was produced by adding 10% CO2 to the inspired gas. ⋯ The increase in Pdi was more than in Group III than in Group II (P<0.05). In Group I, Pdi to each stimulus did not change from hypercapnia-induced values. In conclusion, compared with dopamine, dobutamine is effective in improving hypercapnic depression of diaphragmatic contractility in dogs.
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Pulm Pharmacol Ther · Jan 2004
Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.
In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. ⋯ In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO.
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Pulm Pharmacol Ther · Jan 2004
Inhaled milrinone for the improvement of contractility of fatigued diaphragm in dogs: a dose-ranging study.
The present study was undertaken to evaluate the efficacy of inhaled milrinone on contractility of fatigued diaphragm in dogs. Animals were divided into four groups of seven each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. ⋯ The increase in Pdi was more in Group IV than in Group III (P<0.05). Compared with Group I, Pdi to each stimulus did not change in Group II. In conclusion, inhaled milrinone, in doses more than 0.2 mg/ml, is effective for improving contractility of fatigued diaphragm in dogs.
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Pulm Pharmacol Ther · Jan 2003
ReviewThe effect of anti-integrin monoclonal antibodies on antigen-induced pulmonary inflammation in allergic rabbits.
The integrin adhesion molecules are involved in the recruitment and activation of inflammatory cells at sites of inflammation in a variety of diseases. In the present study, we have investigated the effects of blocking monoclonal antibodies (mAbs) directed against CD49d (alpha(4) integrin), CD18 (beta(2) integrin) and the alpha sub-units of beta(2) integrin CD11a (LFA-1 integrin) and CD11b (Mac-1 integrin), on antigen (Ag)-induced acute bronchoconstriction and cellular recruitment in allergic rabbits in vivo. Inhaled Ag (Alternaria tenuis) challenge of neonatally sensitised rabbits caused an acute bronchoconstriction demonstrated by an increase in lung resistance (R(L)) and decrease in dynamic compliance (C(dyn)) and pulmonary inflammation characterised by an increase in bronchoalveolar lavage (BAL) inflammatory cells, particularly eosinophils, 24 h after challenge. ⋯ The data show that in the allergic rabbit model of asthma, VLA-4 (CD49d/CD29) only, is involved in the acute bronchoconstriction, suggesting an involvement of mast cell degranulation. Furthermore, eosinophil recruitment and activation appears to be mediated by a combination of VLA-4 (CD49d/CD29) and LFA-1 (CD18/CD11a). However in contrast, lymphocyte recruitment appears to be mediated by a combination of LFA-1 (CD18/CD11a) and Mac-1 (CD18/CD11b).