title: Low-dose adrenomedullin-2/intermedin(8-47) reduces pulmonary ischemia/reperfusion injury.
abstract: Adrenomedullin-2/intermedin stabilizes the pulmonary microvascular barrier challenged by application of thrombin ex vivo and by experimental ventilation in vivo. Here, we test the hypothesis that adrenomedullin-2/intermedin(8-47) protects mouse lungs from ischemia/reperfusion injury in vivo. C57BL/6 mice were anesthetized, intubated, ventilated, and heparinized. Blood vessels and the main bronchus of the left lung were clamped for 90min. Thereafter, lungs were reperfused for 120min. Five min before clamping and before reperfusion, mice obtained intravenous injections of adrenomedullin-2/intermedin(8-47). After reperfusion, mice were sacrificed and bronchoalveolar lavage of the left and the right lung was performed separately. The integrity of the blood-air barrier was investigated by electron microscopy using stereological methods. In response to ischemia/reperfusion injury, intraalveolar leukocytes accumulated in the ischemic lung. Two applications of 10ng/kg body weight adrenomedullin-2/intermedin(8-47) dramatically reduced leukocyte infiltration to about 15% (p≤0.001). Also the proportion of the subpopulation of neutrophil granulocytes decreased (12% vs 5%, p=0.013). Electron microscopy revealed a protection of the blood-air barrier by adrenomedullin-2/intermedin(8-47). Adrenomedullin-2/intermedin(8-47) ameliorates early ischemia/reperfusion injury in mouse lungs by protecting the integrity of the blood-air barrier and by potently reducing leukocyte influx into the alveolar space. Adrenomedullin-2/intermedin(8-47) might be of therapeutic interest in lung transplantation and cardiopulmonary bypass.
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany. Electronic address: Christian.Koerner@chiru.med.uni-giessen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kuchenbuch
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University Giessen, UGMLC, Member of the DZL, Giessen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfeil
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University Giessen, UGMLC, Member of the DZL, Giessen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Jung
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Padberg
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University Giessen, UGMLC, Member of the DZL, Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University Giessen, UGMLC, Member of the DZL, Giessen, Germany; Institute of Functional and Applied Anatomy, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the DZL, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Grau
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D015824:Blood-Air Barrier / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D055370:Lung Injury / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009479:Neuropeptides / Q000008:administration & dosage*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009479:Neuropeptides; C514552:intermedin protein, mouse
keywords: Blood–air barrier; Bronchoalveolar lavage; Intermedin; Leukocyte; Stereology