Paradoxical conducting airway responses and heterogeneous regional ventilation after histamine inhalation in rabbit studied by synchrotron radiation CT

1 Department of Physiology, EA4285, Université de Picardie Jules Verne Medical School, and Paediatric Cardiology and Pulmonary Medicine, Centre Hospitalier Universitaire d'Amiens, Amiens, France; 2 European Synchrotron Radiation Facility, Biomedical Beamline - ID17, Grenoble, France; 3 Department of Physics, University of Helsinki, Helsinki; and 4 Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland Submitted 21 April 2008 ; accepted in final form 5 April 2009 We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon-enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals ( n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (s m ), but an increase in s m in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as coefficient of variation (CV) of s m significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree. airways; asthma; histamine; xenon; tomography; X-ray computed; synchrotrons; rabbit Address for reprint requests and other correspondence: S. Bayat, Centre Hospitalier Universitaire d'Amiens, Cardiologie et Pneumo-Allergologie Pédiatriques, 1 Place Victor Pauchet, 80054 Amiens Cedex 1, France (e-mail: bayat.sam{at}chu-amiens.fr )