We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage.
The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein‐free phospholipid based LSF (PL‐LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg−1 body weight and an untreated control group.
Tracheotomized rats (10–12 per dose) were pressure‐controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min−1, inspiration expiration ratio of 1: 2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end‐expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction).
Partial arterial oxygen pressure (Pao2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (Pao2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose‐dependent increase for the Pao2(120′), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose‐dependency. Exosurf did not increase Pao2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse. The bovine and the Recombinant LSF are superior to both synthetic LSF preparations.
In this animal model and under the described specific ventilatory settings, even between bovine LSF preparations there are detectable differences that are pronounced when compared to synthetic LSF without any surfactant proteins. We conclude that the difference between bovine and synthetic LSF preparations can be overcome by addition of the surfactant protein C.
Zardaverine (Byk Gulden, Konstanz, Germany) is a new selective phosphodiesterase (PDE) III/IV inhibitor. The bronchodilating and bronchoprotective potency of zardaverine and the nonselective PDE inhibitor theophylline was compared by measuring typical spontaneous and forced respiratory function parameters in anesthetized female Wistar rats using whole-body plethysmography. Zardaverine (3, 10, 30 mumol/kg) and theophylline (30, 100, 300 mumol/kg), respectively, were given orally in 4% Methocel/0.9% saline solution 20 min before measurement. One week before treatment, control measurements were performed in the same animals after administration of the vehicle. When spontaneously breathing, the 30 mumol/kg zardaverine- (300 mumol/kg theophylline-) treated animals showed significant changes: a 23% (14% ns) decrease in lung resistance and a 43% (25%) increase in dynamic compliance. These changes can be interpreted as an indication of bronchodilation, since quasistatic lung compliance was unchanged. In the acetylcholine challenge test, treatment with only 10 mumol/kg zardaverine (but 300 mumol/kg theophylline) revealed significant changes compared to control measurement: a 37% (28%) lower resistance and 85% (44%) higher compliance. It has been determined that zardaverine is more than 30 times as potent as theophylline in inhibiting acetylcholine-induced bronchospasms, which is also supported by forced expiratory flow data.
The new homoisoflavanone R(-)-3-(4-hydroxybenzyl)-5-hydroxy-6, 7,8-trimethoxychroman-4-one (1) was isolated from the petroleum ether and the diethyl ether extracts of the bulbs of Veltheimia viridifolia (Hyacinthaceae) together with the known homoisoflavanone muscomin (2). The structures of the compounds were elucidated by means of 1H-NMR, 2D 1H-1H-COSY, 13C-NMR, HMQC, HMBC, mass, and CD spectra. Pharmacological testings of the new homoisoflavanone are reported.
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