Dose‐response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS)

Abstract

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.

Secretion of Surfactant Protein C, an Integral Membrane Protein, Requires the N-terminal Propeptide

“…The importance of SP-C for normal lung function is inferred from experiments in which intratracheal administration of surfactant containing SP-C as the sole protein component to preterm animals restored lung function to values comparable with animals treated with native surfactant (3)(4)(5). Collectively, these results suggest that SP-C and SP-B are functionally interchangeable with respect to biophysical activity.…”

Expression of a Human Surfactant Protein C Mutation Associated with Interstitial Lung Disease Disrupts Lung Development in Transgenic Mice

“…Surfactant forms a bioactive film that effectively reduces the amount of work required during inspiration and prevents alveolar collapse at end expiration. The protein components of surfactant, in particular the lipophilic proteins surfactant protein B (SP-B) 1 and surfactant protein C (SP-C), facilitate the adsorption and spreading of lipids during the respiratory cycle and are critical for the formation and maintenance of the surfactant film. The importance of SP-C in mediating this process is underscored by the efficacy of exogenous surfactant preparations containing SP-C as the sole protein component (1)(2)(3).…”

Hot Topics in and New Strategies for Surfactant Research

“…However, mice and humans that lack SP-B also have a deficiency of mature SP-C in their alveoli, because SP-B deficiency disrupts lamellar body formation and the processing of SP-C [6]. Therefore SP-B deficiency results in a combined deficiency of SP-B and SP-C. Surfactants that contain only recombinant SP-C or SP-C analogs can function extremely well in lung injury models of RDS and acute RDS [7,8]. Infants that lack SP-C also have a lethal RDS-like syndrome [9].…”