PMID- 30925204 OWN - NLM STAT- MEDLINE DCOM- 20200214 LR - 20200214 IS - 1742-7843 (Electronic) IS - 1742-7835 (Linking) VI - 125 IP - 3 DP - 2019 Sep TI - Retrograde perfusion in isolated perfused mouse lungs-Feasibility and effects on cytokine levels and pulmonary oedema formation. PG - 279-288 LID - 10.1111/bcpt.13236 [doi] AB - Retrograde lung vascular perfusion can appear in high-risk surgeries. The present report is the first to study long-term retrograde perfusion of isolated perfused mouse lungs (IPLs) and to use the tyrosine kinase ephB4 and its ligand ephrinB2 as potential markers for acute lung injury. Mouse lungs were subjected to anterograde or retrograde perfusion with normal-pressure ventilation (NV) or high-pressure ventilation (=overventilation, OV) for 4 hours. Outcome parameters were cytokine, ephrinB2 and ephB4 levels in perfusate samples and bronchoalveolar lavage (BAL), and the wet-to-dry ratio. Anterograde perfusion was feasible for 4 hours, while lungs receiving retrograde perfusion presented considerable collapse rates. Retrograde perfusion resulted in an increased wet-to-dry ratio when combined with high-pressure ventilation; other physiological parameters were not affected. Cytokine levels in BAL and perfusate, as well as levels of soluble ephB4 in BAL were increased in OV, while soluble ephrinB2 BAL levels were increased in retrograde perfusion. BAL levels of ephrinB2 and ephB4 were also determined in vivo, including mice ventilated for 7 hours with normal-volume ventilation (NVV) or high-volume ventilation (HVV) with increased levels of ephB4 in HVV BAL compared to NVV. Retrograde perfusion in IPL is limited as a routine method to investigate effects due to collapse for yet unclear reasons. If successful, retrograde perfusion has an influence on pulmonary oedema formation. In BAL, ephrinB2 seems to be up-regulated by flow reversal, while ephB4 is a marker for acute lung injury. CI - (c) 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). FAU - Krabbe, Julia AU - Krabbe J AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. AD - Medical Faculty, Institute of Occupational, Social and Environmental Medicine, RWTH Aachen University, Aachen, Germany. FAU - Ruske, Nadine AU - Ruske N AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. FAU - Kanzler, Stephanie AU - Kanzler S AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. FAU - Reiss, Lucy Kathleen AU - Reiss LK AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. FAU - Ludwig, Andreas AU - Ludwig A AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. FAU - Uhlig, Stefan AU - Uhlig S AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. FAU - Martin, Christian AU - Martin C AD - Medical Faculty, Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany. LA - eng GR - 114/16/RWTH Aachen University/ PT - Journal Article DEP - 20190421 PL - England TA - Basic Clin Pharmacol Toxicol JT - Basic & clinical pharmacology & toxicology JID - 101208422 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (EFNB2 protein, mouse) RN - 0 (Ephrin-B2) RN - EC 2.7.10.1 (Ephb4 protein, mouse) RN - EC 2.7.10.1 (Receptor, EphB4) SB - IM MH - Acute Lung Injury/*diagnosis/immunology MH - Animals MH - Biomarkers/analysis MH - Bronchoalveolar Lavage Fluid/chemistry/immunology MH - Cytokines/*analysis/immunology MH - Disease Models, Animal MH - Edema/*diagnosis/immunology MH - Ephrin-B2/analysis MH - Feasibility Studies MH - Female MH - Humans MH - In Vitro Techniques/methods MH - Lung/immunology/*surgery MH - Mice MH - Perfusion/*adverse effects/methods MH - Receptor, EphB4/analysis/immunology MH - Respiration, Artificial/adverse effects/methods MH - Time Factors MH - Up-Regulation OTO - NOTNLM OT - ephB4 OT - ephrinB2 OT - isolated perfused lungs OT - oedema formation OT - retrograde perfusion EDAT- 2019/03/30 06:00 MHDA- 2020/02/15 06:00 CRDT- 2019/03/30 06:00 PHST- 2018/10/12 00:00 [received] PHST- 2019/03/22 00:00 [accepted] PHST- 2019/03/30 06:00 [pubmed] PHST- 2020/02/15 06:00 [medline] PHST- 2019/03/30 06:00 [entrez] AID - 10.1111/bcpt.13236 [doi] PST - ppublish SO - Basic Clin Pharmacol Toxicol. 2019 Sep;125(3):279-288. doi: 10.1111/bcpt.13236. Epub 2019 Apr 21.