Dataset Information

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs.

ABSTRACT:

Background

The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb.

Methods

Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200?mg/kg) and 5 lambs were managed with mechanical ventilation for 120?min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH₂O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant.

Results

Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p?ConclusionsApplying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

SUBMITTER: Zecchi R

PROVIDER: S-EPMC6683365 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs.

Zecchi Riccardo R Franceschi Pietro P Tigli Laura L Ricci Francesca F Boscaro Francesca F Pioselli Barbara B Mileo Valentina V Murgia Xabier X Bianco Federico F Salomone Fabrizio F Schmidt Augusto F AF Hillman Noah H NH Kemp Matthew W MW Jobe Alan H AH

Respiratory research 20190805 1

<h4>Background</h4>The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant ...[more]

PMID: 31382955

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Project description:In mammals, oleic acid (OA) induces pulmonary edema (PE), which can initiate acute lung injury (ALI) and lead to acute respiratory distress syndrome (ARDS). Pulmonary surfactant (PS) plays a key role in a broad range of treatments for ARDS. The aim of the present investigation was to assess changes in the synthesis of phosphatidylcholine (PC) from choline and determine the effect of exogenous PS on its de novo synthesis in rats with OA-induced PE. Experimental rats were randomized into three groups, including a control group, OA-induced PE group, and OA-induced group treated with exogenous PS (OA-PS). Twenty-four rats were sacrificed 4 h after induction of the OA model, and tissue was examined by light and electron microscopy to assess the severity of ALI using an established scoring system at the end of the experiment. After 15 ?Ci 3H-choline chloride was injected intravenously, eight rats in each group were sacrificed at 4, 8, and 16 h. The radioactivity of 3H incorporated into total phospholipid (TPL) and desaturated phosphatidylcholine (DSPC) was measured in bronchoalveolar lavage fluid (BALF) and lung tissue (LT) using a liquid scintillation counter and was expressed as counts per minute (CPM). Results showed that TPL, DSPC, and the ratio of DSPC/total protein (TP) in lung tissue decreased 4 h after challenge with OA, but the levels recovered after 8 and 16 h. At 8 h after injection, 3H-TPL and 3H-DSPC radioactivity in the lungs reached its peak. Importantly, 3H-DSPC CPM were significantly lower in the PS treatment group (LT: Control: 62327 ± 9108; OA-PE: 97315 ± 10083; OA-PS: 45127 ± 10034, P < 0.05; BALF: Control: 7771 ± 1768; OA-PE: 8097 ± 1799; OA-PE: 3651 ± 1027, P < 0.05). Furthermore, DSPC secretory rate (SR) in the lungs was significantly lower in the PS treatment group at 4 h after injection (Control: 0.014 ± 0.003; OA-PE: 0.011 ± 0.004; OA-PS: 0.023 ± 0.006, P < 0.05). Therefore, we hypothesize that exogenous PS treatments may adversely affect endogenous de novo synthetic and secretory phospholipid pathways via feedback inhibition. This novel finding reveals the specific involvement of exogenous PS in endogenous synthetic and secretory phospholipid pathways during the treatment of ARDS. This information improves our understanding of how PS treatment is beneficial against ARDS and opens new opportunities for expanding its use.

Dataset Information

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs.

Background

Methods

Results

Publications

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs.

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