Effects of lung surfactant factor (LSF) treatment on gas exchange and histopathological changes in an animal model of adult respiratory distress syndrome (ARDS): comparison of recombinant LSF with bovine LSF.
Repetitive lung lavage of adult rats leads to lung injury similar to ARDS resulting in poor gas exchange, protein leakage and infiltration of polymorphonuclear neutrophils (PMN) into the alveolar spaces (J Appl Physiol 1983; 55: 131-138). In a previous dose response comparison we have demonstrated that poor gas exchange could be improved by lung surfactant factor (LSF) instillation soon after lavage. Since Surfacten (Tokyo Tanabe Co. Ltd., Tokyo, Japan) was described in vitro to inhibit PMN activity, we compared this preparation with a Recombinant LSF preparation (Byk Gulden, Konstanz, Germany; phospholipids plus human identical surfactant protein C) at doses of 25, 50 and 100 mg/kg body weight. Their efficacy was compared with an untreated control group with respect to improving gas exchange, inhibition of hyaline membrane formation and inhibition of the inflammatory response after multiple lavage. Tracheotomized rats were pressure-controlled ventilated (Siemens Servo Ventilator 900C, Sweden) with 100% oxygen at a respiratory rate of 30 breaths/min, 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 was reduced from 8 to 6 cmH2O (first PEEP-reduction), from 6 to 3 (second reduction) and from 3 to 0 cmH2O (third reduction) and finally raised to 8 cmH2O. Results for the averaged partial arterial oxygen pressure [PaO2 (mmHg)] of the 2 h period [PaO2(5'-120')] and for the PaO2 during the second PEEP reduction [PaO2(PEEP23/3] were calculated. Both LSF preparations caused a dose-dependent increase of the PaO2 (5'-120') and the PaO2(PEEP23/3). Similarly, the formation of hyaline membranes was inhibited by both LSF preparations in a dose-dependent manner. Inhibition of the inflammatory response (infiltration of PMN) was not effected by either of the LSF preparations at any dose level. The described variations in ventilator settings are useful to evaluate the deflation stability and re-expansion potential of different LSF preparations. The reported results give evidence that prevention of atelectasis by LSF treatment improves gas exchange and inhibits formation of hyaline membranes, leading to the conclusion that LSF treatment may be a promising therapy in ARDS patients.
Häfner
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Germann
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Hauschke
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D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D001261:Pulmonary Atelectasis / Q000517:prevention & control; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D011663:Pulmonary Surfactants; D011994:Recombinant Proteins