Respiratory changes in a murine model of spontaneous systemic lupus erythematosus.

The pathophysiology of systemic lupus erythematosus (SLE) has been very well described in many organs. However, the relation between extracellular matrix changes and lung dynamic mechanical behaviour deserves elucidation. To that end, pulmonary mechanics, lung morphometry and the amount of collagen and elastic fibres in the alveolar septa were analysed in mice with SLE [NZB/W (New Zealand Black/White) F1] and non-diseased NZW mice (control). Static (E(st)) and dynamic (E(dyn)) elastances, difference between dynamic and static elastances (DeltaE), airway resistance (R(aw)) and viscoelastic/inhomogeneous pressure (DeltaP(2)) were determined by the end-inflation occlusion method. Lungs were removed and prepared for histology. E(st), E(dyn), DeltaE and DeltaP(2) were higher in SLE than in control group, while R(aw) was similar in both groups. SLE group showed alveolar collapse and increased amount of elastic and collagen fibres. In conclusion, SLE mice showed an increase in elastic and viscoelastic/inhomogeneous pressures that was accompanied by deposition of collagen and elastic fibres in the alveolar septa.

Evaluation of respiratory mechanics and lung histology in a model of atelectasis.

To develop a reproducible model of atelectasis, 15 mechanically ventilated Wistar rats were wrapped around the thorax/abdomen with a sphygmomanometer. The cuff was inflated to transpulmonary pressures (PL) of -4 cmH2O (group A) and -8 cmH2O (group B) for 5 sec. Group C was not compressed. Airflow, volume, tracheal and oesophageal pressures were registered. Respiratory system (rs), lung (L), and chest wall resistive (DeltaP1), viscoelastic/inhomogeneous pressures (DeltaP2), DeltaPtot (=DeltaP1 + DeltaP2), static (Est) and dynamic (Edyn) elastances, and DeltaE (=Edyn - Est) were determined before and after compression. In A, respiratory mechanics remained unaltered. In B, Est,rs (+99%), Est,L (+111%), DeltaE,rs (+41%), DeltaE,L (+73%), DeltaP1,rs (+45%), DeltaP1,L (+44%), DeltaP2,rs (+41%), DeltaP2,L (+69%), DeltaPtot,rs (+40%), and DeltaPtot,L (+58%) increased after compression. Mean alveolar diameter and bronchiolar lumen decreased in A, and were even smaller in B. In conclusion, chest wall compression with PL of -8 cmH2O yielded a reproducible alveolar collapse, which resulted in increased elastic, resistive and viscoelastic/inhomogeneous pressures.

Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury.

In vivo (lung resistive and viscoelastic pressures and static elastance) and in vitro (tissue resistance, elastance, and hysteresivity) respiratory mechanics were analyzed 1 and 30 days after saline (control) or paraquat (P [10 and 25 mg/kg intraperitoneally]) injection in rats. Additionally, P10 and P25 were treated with methylprednisolone (2 mg/kg intravenously) at 1 or 6 hours after acute lung injury (ALI) induction. Collagen and elastic fibers were quantified. Lung resistive and viscoelastic pressures and static elastance were higher in P10 and P25 than in the control. Tissue elastance and resistance augmented from control to P10 (1 and 30 days) and P25. Hysteresivity increased in only P25. Methylprednisolone at 1 or 6 hours attenuated in vivo and in vitro mechanical changes in P25, whereas P10 parameters were similar to the control. Collagen increment was dose and time dependent. Elastic fibers increased in P25 and at 30 days in P10. Corticosteroid prevented collagen increment and avoided elastogenesis. In conclusion, methylprednisolone led to a complete maintenance of in vivo and in vitro respiratory mechanics in mild lesion, whereas it minimized the changes in tissue impedance and extracellular matrix in severe ALI. The beneficial effects of the early use of steroids in ALI remained unaltered at Day 30.