232 - Preterm lambs delivered from 110d gestation and mechanically ventilated for 3d had more severe alveolar simplification and respiratory mechanics impairment than at later gestation ages

Publication Number: 232.6406

Andrew Rebentisch, University of Utah School of Medicine, Salt Lake CIty, UT, United States; Jakob Van Boerum, University of Utah Health, Salt Lake City, UT, United States; Zoe Vordos, University of Utah School of Medicine, Salt Lake City, UT, United States; Emily Major, University of Utah School of Medicine, Ogden, UT, United States; Linden Carter, University of Utah, Salt Lake City, UT, United States; Mike Borton, University of Utah School of Medicine, Boise, ID, United States; Chiara Veneroni, Politecnico di Milano, Milan, Lombardia, Italy; Davide Bizzotto, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Lombardia, Italy; Anna Lavizzari, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy; Raffaele L. Dellaca', Politecnico di Milano University, Milano, Lombardia, Italy; Kurt H.. Albertine, University of Utah, Salt Lake City, UT, United States; Matthew S. Douglass, University of Utah School of Medicine, Salt Lake City, UT, United States; Mar Janna Dahl, University of Utah School of Medicine, Salt Lake City, UT, United States

Background: A limitation of our preterm lamb model is that the lambs are delivered during the saccular stage of lung development. We showed that 3d of invasive mechanical ventilation (IMV) of lambs delivered at ~128-130d of gestation have alveolar simplification that persists to 2- and 5-months corrected postnatal age (Dahl, 2018, AJP 315:L816-L833; Dahl, 2021, AJP 32:L248-L262). Unknown is whether preterm lambs born earlier in gestation, during the canalicular stage of lung development, have more severe alveolar simplification at the end of 3d of mechanical ventilation.

Objective: The aim of the present study was to deliver preterm lambs at earlier gestational ages (110-120d), equivalent to 22-25 weeks human gestation.

Design/Methods: Preterm lambs were delivered by Cesarean-section at (1) 110d (n=3); (2) 115d (n=4); (3) 120d (n=8); or (4) 130d (n=4) gestation (Table). All lambs were exposed to antenatal steroids, given surfactant before delivery, and caffeine citrate after delivery. All lambs were intubated at birth, resuscitated by IMV, and continued IMV respiratory support for 3d. Respiratory mechanics were measured by forced oscillation technique (Resuscitator, Politecnico di Milano) and at the ventilator. Quantitative histology assessed indices of alveolar formation and smooth muscle area around terminal bronchioles.

Results: 110d gestation preterm lambs had significantly thicker distal airspace walls (8.5±1.1µm; *p < 0.05, Tukey ANOVA test) compared to 120d (6.1±1.3 µm) and 130d (5.6±0.7 µm) preterm lambs. 115d gestation preterm lambs also had significantly thicker distal airspace walls (8.3±0.6 µm; *p < 0.05) compared to 120d and 130d gestation preterm lambs. All preterm lambs had significantly lower volume density of secondary septa compared to term lambs (Reyburn, 2008, AJRCCM 178:407-418). However, no statistical differences were detected among the 4 groups for volume density of secondary septation or smooth muscle area around terminal bronchioles. Respiratory mechanics analyses are ongoing. Initial results for resistance and dynamic compliance are shown in the figure.

Conclusion(s): Preterm lambs delivered at the canalicular or early saccular stages of lung development and mechanically ventilated for 3d had more structural evidence of alveolar simplification than preterm lambs delivered at the saccular/alveolar stages and mechanically ventilated for 3d. The earlier gestation model provides a unique opportunity to assess consequences of treatments to minimize development of neonatal chronic lung disease in very preterm lambs.

Experimental groups and gestational ages
Experimental Groups

Early Gestation Ventilator Resistance and Compliance
Resistance and dynamic compliance (Cdyn)