Cargando…
Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs
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 su...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683365/ https://www.ncbi.nlm.nih.gov/pubmed/31382955 http://dx.doi.org/10.1186/s12931-019-1144-5 |
_version_ | 1783442076253290496 |
---|---|
author | Zecchi, Riccardo Franceschi, Pietro Tigli, Laura Ricci, Francesca Boscaro, Francesca Pioselli, Barbara Mileo, Valentina Murgia, Xabier Bianco, Federico Salomone, Fabrizio Schmidt, Augusto F. Hillman, Noah H. Kemp, Matthew W. Jobe, Alan H. |
author_facet | Zecchi, Riccardo Franceschi, Pietro Tigli, Laura Ricci, Francesca Boscaro, Francesca Pioselli, Barbara Mileo, Valentina Murgia, Xabier Bianco, Federico Salomone, Fabrizio Schmidt, Augusto F. Hillman, Noah H. Kemp, Matthew W. Jobe, Alan H. |
author_sort | Zecchi, Riccardo |
collection | PubMed |
description | 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 cmH(2)O 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 < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. CONCLUSIONS: Applying 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1144-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6683365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66833652019-08-09 Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs Zecchi, Riccardo Franceschi, Pietro Tigli, Laura Ricci, Francesca Boscaro, Francesca Pioselli, Barbara Mileo, Valentina Murgia, Xabier Bianco, Federico Salomone, Fabrizio Schmidt, Augusto F. Hillman, Noah H. Kemp, Matthew W. Jobe, Alan H. Respir Res Research 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 cmH(2)O 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 < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. CONCLUSIONS: Applying 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1144-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-05 2019 /pmc/articles/PMC6683365/ /pubmed/31382955 http://dx.doi.org/10.1186/s12931-019-1144-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zecchi, Riccardo Franceschi, Pietro Tigli, Laura Ricci, Francesca Boscaro, Francesca Pioselli, Barbara Mileo, Valentina Murgia, Xabier Bianco, Federico Salomone, Fabrizio Schmidt, Augusto F. Hillman, Noah H. Kemp, Matthew W. Jobe, Alan H. Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title | Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title_full | Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title_fullStr | Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title_full_unstemmed | Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title_short | Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
title_sort | mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683365/ https://www.ncbi.nlm.nih.gov/pubmed/31382955 http://dx.doi.org/10.1186/s12931-019-1144-5 |
work_keys_str_mv | AT zecchiriccardo massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT franceschipietro massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT tiglilaura massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT riccifrancesca massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT boscarofrancesca massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT piosellibarbara massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT mileovalentina massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT murgiaxabier massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT biancofederico massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT salomonefabrizio massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT schmidtaugustof massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT hillmannoahh massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT kempmattheww massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs AT jobealanh massspectrometryimagingasatoolforevaluatingthepulmonarydistributionofexogenoussurfactantinprematurelambs |