{"doi":"10.3389/fphys.2025.1602578","title":"Computationally-directed mechanical ventilation in a porcine model of ARDS","abstract":"Background Despite the implementation of protective mechanical ventilation, ventilator-induced lung injury remains a significant driver of ARDS-associated morbidity and mortality. Mechanical ventilation must be personalized and adaptive for the patient and evolving disease course to achieve sustained improvements in patient outcomes. In this study, we modified a military-grade transport ventilator to deliver the airway pressure release ventilation (APRV) modality. We developed a computationally-directed (CD) method of adjusting the expiratory duration (T Low ) during APRV using physiologic feedback to reduce alveolar derecruitment and tested this modality in a porcine model of moderate-to-severe ARDS. Methods Female Yorkshire-cross pigs (n = 27) were ventilated using a ZOLL EMV+® 731 Series ventilator during general anesthesia and subjected to a heterogeneous Tween lung injury followed by injurious mechanical ventilation. Animals were subsequently ventilated for 6 hours under general anesthesia after randomization to one of three groups: V T 6 (n = 9) with a tidal volume (V T ) of 6 mL/kg and stepwise adjustments in PEEP and FiO 2 ; V T 10 (n = 9) with V T of 10 mL/kg and PEEP of 5 cmH 2 O; CD-APRV group (n = 9) with computationally-directed adjustments in T Low based on a nonlinear equation of motion to describe respiratory mechanics. Results are reported as median [interquartile range]. Results All groups developed moderate-to-severe ARDS and had similar recovery in lung injury, with all demonstrating final PaO 2 :FiO 2 > 300 mmHg (V T 6: 415.5 [383.0–443.4], V T 10: 353.3 [297.3–397.7], CD-APRV: 316.6 [269.8–362.4]; p = 0.12). PaCO 2 was significantly higher in the V T 6 group compared with the CD-APRV group (59.3 [52.3–60.1] mmHg vs. 38.5 [32.7–52.2] mmHg, p = 0.04) but not significantly different from the V T 10 group (47.5 [45.3–54.4] mmHg; p = 0.32 vs. V T 6) despite having a significantly higher respiratory rate (30.0 [30.0–32.0] breaths/min) compared with V T 10 (12.0 [12.0–15.0] breaths/min, p = 0.001) and CD-APRV (14.0 [14.0–14.0] breaths/min, p < 0.001) groups at the study end. Conclusion We successfully implemented a computationally directed APRV modality on a transport ventilator, adjusting T Low based on respiratory mechanics. This study demonstrated that CD-APRV can be safely used, with the advantage of guiding expiratory duration adjustments based on physiologic feedback from the lungs.","journal":"Frontiers in Physiology","year":2025,"id":583309,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1295771,"name":"A. Fonseca Cruz","orcid":"0000-0001-6969-1223","position":1,"is_corresponding":false},{"id":452602,"name":"Jacob Herrmann","orcid":"0000-0001-5046-5592","position":2,"is_corresponding":false},{"id":282284,"name":"Joshua Satalin","orcid":"0000-0002-7582-2493","position":3,"is_corresponding":false},{"id":1293188,"name":"Sarah Satalin","orcid":null,"position":4,"is_corresponding":false},{"id":1495917,"name":"Brian P. Harvey","orcid":null,"position":5,"is_corresponding":false},{"id":1495918,"name":"Dorian LeCroy","orcid":null,"position":6,"is_corresponding":false},{"id":1495919,"name":"George Beck","orcid":null,"position":7,"is_corresponding":false},{"id":1293187,"name":"Mark Lutz","orcid":null,"position":8,"is_corresponding":false},{"id":1495920,"name":"Jacob Charlamb","orcid":null,"position":9,"is_corresponding":false},{"id":1495921,"name":"Joshua R. Kenna","orcid":null,"position":10,"is_corresponding":false},{"id":148315,"name":"Mark S. Baker","orcid":"0000-0001-5858-4035","position":11,"is_corresponding":false},{"id":282281,"name":"Gary F. Nieman","orcid":"0000-0002-4541-4472","position":12,"is_corresponding":false},{"id":493577,"name":"David W. Kaczka","orcid":"0000-0003-4378-5242","position":13,"is_corresponding":false},{"id":282289,"name":"Michaela Kollisch‐Singule","orcid":"0000-0001-9422-1063","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:59:03.725721Z","pmid":"41384246","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}