A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-Csurfactant

The influence of lavage volume, and ravage repetition with physiological sa line solution (groups 1-3: 3x4, 4x4, 5x4, groups 7-9. 3x8, 5x8, 7x8, mt per animal) was studied in a rat lung lavage model of the acute respiratory di stress syndrome (ARDS). Anesthetized and tracheotomized rats (12 rats/group ) were pressure-controlled ventilated with 100% oxygen at a respiratory rat e of 30 breaths/min, inspiration: expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure of 8 cm H2O duri ng the whole experimental period. To investigate the influence of therapeut ic treatment, a recombinant surfactant protein C (rSP-C) containing surfact ant was used. Therefore, rats which received a lavage of 4x4 mt per animal (groups 4 to 6) or 7x8 mt per animal (groups 10-12) were treated intratrach eally with surfactant doses of 12.5, 25, or 100 mg phospholipids (PL) per k g body weight (bw). In all groups, partial arterial oxygen pressures (PaO2, mm Hg) and partial arterial carbon dioxide pressures (PaCO2, mm Hg) were d etermined 30 min before, directly after, and 5, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. Additionally, animals were euthanized 21 0 min after the last lavage for semiquantitative histopathological grading of coded lung slides. Grading was performed with respect to the severity of hyaline membrane formation (HM), margination and infiltration of polymorph onuclear neutrophil leukocytes (PMNL) into the lung alveoli and interstitia l and intraalveolar edema (E). The intrapulmonary distribution of intratrac heally applied rSP-C was estimated in selected lung slides stained with pol yclonal anti-rSP-C antibody and was compared to unlavaged control rats and unlavaged rats which received 100 mg/kg bw rSP-C. The repetitive lavage dep leted the lung from its natural surfactant resources leading to a pathophys iological cascade similar to that of the acute respiratory distress syndrom e. PaO2 levels and HM formation showed a ravage-induced decrease. Both chan ges were significantly dependent on the repetition and volume of the lavage ; however, the parameters PMNL and E did not show such a dependence. Treatm ent with rSP-C surfactant significantly improved oxygenation and reduced HM -formation in a dose-dependent manner independent from the lavage volume. A ll doses of rSP-C surfactant showed no clear influence on the parameters PM NL and E independently from the lavage volume. In lavaged rat lungs (ARDS-m odel), the exogenously applied rSP-C was distributed homogeneously along th e alveolar lining. Unlavaged rats that received a similar dose of rSP-C sho wed a marked inhomogeneous extracellular distribution, mainly associated wi th larger bronchi, while the type II pneumocytes were stained positively in unlavaged control and unlavaged rSP-C treated rats. Conclusion: This model mimics very closely the wide spectrum of the clinica l situation of human acute lung injury (ALI) because the variation of lavag e volume and repetition lead to reproducible different severity grades and states of ALI. The significant reduction of pathognomic changes due to trea tment with rSP-C surfactant showed that this is a useful model to estimate the influence of therapeutic concepts in ALI and ARDS. (C) 1999 Elsevier Sc ience Inc. All rights reserved.