Search

Aspiration pneumonitis can lead to alveolar surfactant dysfunction. We employed a murine model of unilateral aspiration to compare surfactant synthesis in the injured (I) and noninjured (NI) contralateral lung. Mice were instilled with hydrochloric acid in the right bronchus and, after 18 h, an intraperitoneal dose of deuterated water was administered as precursor of disaturated phosphatidylcholine (DSPC)-palmitate. Selected bronchoalveolar lavage fluid (BALF) was collected at scheduled time points and lungs were removed. We measured DSPC-palmitate synthesis in lung tissue and secretion in BALF by gas chromatographyisotope ratio mass spectrometry, together with total proteins and myeloperoxidase activity (MPO) by spectrophotometry. BALF total proteins and MPO were significantly increased in the I lungs compared with NI and naïve control lungs. The DSPC pool size was significantly lower in the BALF of the I lungs compared with naïve controls. DSPC synthesis was accelerated in the I and NI lungs. DSPC secretion of the I lungs was similar to their respective naïve controls, and it was markedly lower compared with their respective NI contralateral lungs. DSPC synthesis and secretion were faster, especially in the NI lungs, compared with naïve control lungs, as a possible compensatory mechanism due to a cross-talk between the lungs triggered by inflammation, hyperventilation, and/or undetermined type II cell reaction to the injury. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. Methods: Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[F]fluorine-2-deoxy- d-glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. Results: Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [F]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. Conclusions: This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury. [ABSTRACT FROM AUTHOR]

Abstract: Aspiration pneumonitis, a direct cause of acute lung injury, is associated to a severe deterioration of lung function due in part to endogenous surfactant system impairment. We evaluated the effects of selective exogenous surfactant administration in a murine model of acid-induced lung injury both at short and long term. Hydrochloric acid was instilled into the right bronchus of the mice (0.1 M, 1.5 ml/kg). Six hours from acid instillation, they received, in the injured lung, a 1 ml/kg bolus of porcine surfactant (Curosurf®) 40 or 80 mg phospholipids/ml (Surf40 or Surf80), or saline (0.9% NaCl, vehicle) Functional, biochemical, histological and inflammatory results were obtained 24 h after injury. In the Surf80 and vehicle group, lung mechanics and histology were assessed again after two weeks. Micro-Computed Tomography scans were performed at 24 h and two weeks. 24 h after injury in the Surf80 group respiratory system compliance and oxygenation were significantly improved compared to the vehicle, while neutrophilic fraction in bronchoalveolar lavage was significantly lower. Surfactant-treated mice maintained a better compliance and a significantly reduced inflammatory infiltrate also two weeks after treatment compared to vehicle. Micro-Computed Tomography scan suggested a more pronounced reduction of injury in surfactant-treated animals two weeks after injury (p = 0.09). We showed a beneficial effect on lung function of a single bolus of exogenous surfactant in unilateral acid-induced lung injury up to two weeks after treatment. Our results may suggest a role of surfactant replacement in modulating spontaneous evolution of injury. [Copyright &y& Elsevier]