Dietrich Häfner

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

1 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. 2 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. 3 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). 4 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. 5 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.

Comparison of rSP-C surfactant with natural and synthetic surfactants after late treatment in a rat model of the acute respiratory distress syndrome

1 In a previous paper we showed that an SP‐C containing surfactant preparation has similar activity as bovine‐derived surfactants in a rat lung lavage model of the adult respiratory distress syndrome. In this study surfactant was given ten minutes after the last lavage (early treatment). In the present investigation we were interested how different surfactant preparations behave when they are administered 1 h after the last lavage (late treatment). 2 Four protein containing surfactants (rSP‐C surfactant, bLES, Infasurf and Survanta) were compared with three protein‐free surfactants (ALEC, Exosurf and the phospholipid (PL) mixture of the rSP‐C surfactant termed PL surfactant) with respect to their ability to improve gas exchange in this more stringent model when surfactant is given one hour after the last lavage. For better comparison of the surfactants the doses were related to phospholipids. The surfactants were given at doses of 25, 50 and 100 mg kg−1 body weight. The surfactants were compared to an untreated control group that was only ventilated for the whole experimental period. 3 Tracheotomized rats (8–12 per dose and surfactant) 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 of 28 cmH2O at positive endexpiratory pressure (PEEP) of 8 cmH2O. Animals were ventilated for one hour after the last lavage and thereafter the surfactants were intratracheally instilled. During the whole experimental period the ventilation was not changed. 4 Partial arterial oxygen pressures (Pao2, mmHg) at 30 min and 120 min after treatment were used for statistical comparison. All protein containing surfactants caused a dose‐dependent increase of the reduced Pao2 values at 30 min after treatment. The protein‐free surfactants showed only weak dose‐dependent increase in Pao2 values at this time. This difference between the protein‐containing and the protein‐free surfactants was even more pronounced when comparing the Pao2 values at 120 min after treatment. Only rSP‐C surfactant, bLES and Infasurf showed a dose‐dependent increase in Pao2 at this time. 5 With this animal model of late treatment it is possible even to differentiate between bovine derived surfactants. The differences between protein‐containing and protein‐free surfactants become even more pronounced. From the comparison of rSP‐C surfactant with bovine‐derived surfactants and the PL surfactant without rSP‐C, it can be concluded that addition of rSP‐C is sufficient to achieve the same activity as that of natural surfactants.