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 re...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-019-1144-5 |
| _version_ | 1818511263982944256 |
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| author | Riccardo Zecchi Pietro Franceschi Laura Tigli Francesca Ricci Francesca Boscaro Barbara Pioselli Valentina Mileo Xabier Murgia Federico Bianco Fabrizio Salomone Augusto F. Schmidt Noah H. Hillman Matthew W. Kemp Alan H. Jobe |
| author_facet | Riccardo Zecchi Pietro Franceschi Laura Tigli Francesca Ricci Francesca Boscaro Barbara Pioselli Valentina Mileo Xabier Murgia Federico Bianco Fabrizio Salomone Augusto F. Schmidt Noah H. Hillman Matthew W. Kemp Alan H. Jobe |
| author_sort | Riccardo Zecchi |
| collection | DOAJ |
| description | 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 < 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. |
| first_indexed | 2024-12-10T23:30:59Z |
| format | Article |
| id | doaj.art-979ca60013de43c6880ec022810ad441 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-10T23:30:59Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-979ca60013de43c6880ec022810ad4412022-12-22T01:29:23ZengBMCRespiratory Research1465-993X2019-08-0120111210.1186/s12931-019-1144-5Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambsRiccardo Zecchi0Pietro Franceschi1Laura Tigli2Francesca Ricci3Francesca Boscaro4Barbara Pioselli5Valentina Mileo6Xabier Murgia7Federico Bianco8Fabrizio Salomone9Augusto F. Schmidt10Noah H. Hillman11Matthew W. Kemp12Alan H. Jobe13Mass Spectrometry Service Center (CISM), University of FlorenceComputational Biology, Research and Innovation Centre, Fondazione Edmund MachPreclinical R&D, Chiesi FarmaceuticiPreclinical R&D, Chiesi FarmaceuticiMass Spectrometry Service Center (CISM), University of FlorencePreclinical R&D, Chiesi FarmaceuticiPreclinical R&D, Chiesi FarmaceuticiScientific ConsultancyPreclinical R&D, Chiesi FarmaceuticiPreclinical R&D, Chiesi FarmaceuticiDivision of Neonatology and Pulmonary Biology, Cincinnati Children’s HospitalDivision of Neonatology, Cardinal Glennon Children’s Hospital, Saint Louis UniversityDivision of Obstetrics and Gynecology, University of Western AustraliaDivision of Neonatology, Cardinal Glennon Children’s Hospital, Saint Louis UniversityAbstract 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 < 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.http://link.springer.com/article/10.1186/s12931-019-1144-5SurfactantCHF5633Mass spectrometry imagingRespiratory distress syndromePremature lambs |
| spellingShingle | Riccardo Zecchi Pietro Franceschi Laura Tigli Francesca Ricci Francesca Boscaro Barbara Pioselli Valentina Mileo Xabier Murgia Federico Bianco Fabrizio Salomone Augusto F. Schmidt Noah H. Hillman Matthew W. Kemp Alan H. Jobe Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs Respiratory Research Surfactant CHF5633 Mass spectrometry imaging Respiratory distress syndrome 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 | Surfactant CHF5633 Mass spectrometry imaging Respiratory distress syndrome Premature lambs |
| url | http://link.springer.com/article/10.1186/s12931-019-1144-5 |
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