On the crucial ventilatory setting adjustment from two- to one-lung ventilation.

Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.

Effects of dexmedetomidine on respiratory mechanics and control of breathing in normal rats.

Dexmedetomidine is a highly selective and specific alpha(2)-adrenergic agonist, with sedative, analgesic, and sympatholytic activities. The aim of the present study was to define the effects of DMED in respiratory mechanics in normal rats. In addition, lung morphometry was studied to determine whether the physiological changes reflected underlying morphological changes defining the sites of action of dexmedetomidine. Arterial blood gases were also determined. Twelve adult Wistar rats were randomly assigned to two groups of six animals each: PENTO and DMED. In PENTO group animals were sedated (diazepam, 5mg, i.p.) and anaesthetised with pentobarbital sodium (20mgkg(-1) i.p.). The rats of the DMED group received dexmedetomidine (250mugkg(-1) i.p. followed by intravenous infusion of 0.5mugkg(-1)h(-1)). In spontaneously breathing rats, minute ventilation, respiratory frequency, and neuromuscular inspiratory drive were lower in dexmedetomidine group, which also presented hypercapnia, whereas tidal volume, inspiratory, expiratory, and total respiratory cycle times were higher in dexmedetomidine group compared to the PENTO group. During mechanical ventilation, respiratory mechanical parameters were similar in both groups. These findings were supported by the absence of histological changes. In conclusion, under the conditions studied, dexmedetomidine did not change respiratory mechanical parameters and lung histology, but induced ventilatory depression.

Lung parenchyma remodeling in a murine model of chronic allergic inflammation.

This study tested the hypotheses that chronic allergic inflammation induces not only bronchial but also lung parenchyma remodeling, and that these histologic changes are associated with concurrent changes in respiratory mechanics. For this purpose, airway and lung parenchyma remodeling were evaluated by quantitative analysis of collagen and elastin, immunohistochemistry (smooth-muscle actin expression, eosinophil, and dendritic cell densities), and electron microscopy. In vivo (airway resistance, viscoelastic pressure, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics were also analyzed. BALB/c mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. A marked eosinophilic infiltration was seen in lung parenchyma and in large and distal airways. Neutrophils, lymphocytes, and dendritic cells also infiltrated the lungs. There was subepithelial fibrosis, myocyte hypertrophy and hyperplasia, elastic fiber fragmentation, and increased numbers of myofibroblasts in airways and lung parenchyma. Collagen fiber content was increased in the alveolar walls. The volume proportion of smooth muscle-specific actin was augmented in distal airways and alveolar duct walls. Airway resistance, viscoelastic pressure, static elastance, and tissue elastance and resistance were significantly increased. In conclusion, prolonged allergen exposure induced remodeling not only of the airway wall but also of the lung parenchyma, leading to in vivo and in vitro mechanical changes.

Time course of respiratory mechanics and pulmonary structural remodelling in acute lung injury.

The aim of this study was to evaluate the time course of in vivo and in vitro respiratory mechanics and examine whether these parameters could reflect the temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.) injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue resistances increased from control in PQ1 and PQ3 and returned to control values in PQ8, in accordance with the magnitude of bronchoconstriction. Viscoelastic/inhomogeneous pressure, tissue elastance, the number of polymorphonuclear cells, and collagen fibre content in lung parenchyma increased in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1, returned to control values after 3 weeks, and was correlated with the volume fraction of collapsed alveoli. In conclusion, there is a restoration of normal alveolar-capillary lung units with a gradual improvement in airway and tissue resistances and static elastance. However, the on-going fibrotic process kept elevated tissue elastance and viscoelastic/inhomogeneous pressure.