Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs.
CHF5633
Mass spectrometry imaging
Premature lambs
Respiratory distress syndrome
Surfactant
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
05 Aug 2019
05 Aug 2019
Historique:
received:
07
05
2019
accepted:
24
07
2019
entrez:
7
8
2019
pubmed:
7
8
2019
medline:
29
1
2020
Statut:
epublish
Résumé
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. 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 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. 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.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
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.
Identifiants
pubmed: 31382955
doi: 10.1186/s12931-019-1144-5
pii: 10.1186/s12931-019-1144-5
pmc: PMC6683365
doi:
Substances chimiques
CHF5633
0
Peptide Fragments
0
Phosphatidylcholines
0
Pulmonary Surfactant-Associated Protein B
0
Pulmonary Surfactant-Associated Protein C
0
Pulmonary Surfactants
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
175Références
J Biol Chem. 2001 May 4;276(18):14658-64
pubmed: 11278984
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6366-71
pubmed: 11344267
Crit Care Med. 2002 May;30(5):1083-90
pubmed: 12006806
J Proteome Res. 2004 Mar-Apr;3(2):289-95
pubmed: 15113106
J Proteome Res. 2006 Feb;5(2):262-9
pubmed: 16457591
Curr Opin Chem Biol. 2007 Feb;11(1):29-35
pubmed: 17185024
Pediatrics. 1992 Jan;89(1):13-20
pubmed: 1727997
Pediatr Res. 2010 Sep;68(3):193-8
pubmed: 20531255
Biophys J. 2010 Nov 17;99(10):3290-9
pubmed: 21081077
Pediatr Pulmonol. 2011 Oct;46(10):991-9
pubmed: 21520434
Pediatr Res. 2012 Jul;72(1):32-7
pubmed: 22465908
Reprod Toxicol. 2012 Sep;34(2):204-15
pubmed: 22659287
PLoS One. 2012;7(7):e39392
pubmed: 22808033
J Proteomics. 2012 Aug 30;75(16):5106-5110
pubmed: 22842151
PLoS One. 2012;7(10):e47631
pubmed: 23091635
Pediatr Res. 2013 May;73(5):639-46
pubmed: 23403804
Neonatology. 2015;107(4):277-82
pubmed: 25765935
Bioanalysis. 2015;7(20):2649-56
pubmed: 26495807
Pediatr Res. 2017 Feb;81(2):369-375
pubmed: 27973472
Pediatr Pulmonol. 2017 Jul;52(7):929-938
pubmed: 28221717
Arch Dis Child Fetal Neonatal Ed. 2017 Nov;102(6):F497-F503
pubmed: 28465315
J Biophotonics. 2019 Jun;12(6):e201800052
pubmed: 30597770
Am J Physiol Lung Cell Mol Physiol. 2019 Apr 1;316(4):L589-L597
pubmed: 30675804
Eur J Biochem. 1988 Mar 15;172(3):521-5
pubmed: 3350011
J Clin Invest. 1984 Mar;73(3):848-56
pubmed: 6546766
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7794-8
pubmed: 7644495
J Appl Physiol (1985). 1994 Jan;76(1):45-55
pubmed: 8175544
Pediatr Res. 1993 Aug;34(2):154-8
pubmed: 8233717
Pediatr Res. 1993 Oct;34(4):490-4
pubmed: 8255683
Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):366-75
pubmed: 8756808
Lung. 1997;175(1):1-39
pubmed: 8959671
Anal Chem. 1997 Dec 1;69(23):4751-60
pubmed: 9406525
Intensive Care Med. 1997 Oct;23(10):1070-6
pubmed: 9407243