Respiratory Physiology & Neurobiology 179 (2011) 326–333 Contents lists available at SciVerse ScienceDirect Respiratory Physiology & Neurobiology jou rn al h om epa ge: www.elsevier.com/locate/resphysiol Respiratory mechanics and lung tissue remodeling in a hepatopulmonary syndrome rat model César Augusto Melo-Silva a,∗ , Eduardo Gaio a , José E. Trevizoli b , Caio S. Souza a , Alessandra S. Gonc ¸ alves a , Guilherme C.C. Sousa a , Gustavo Takano c , Paulo Tavares a , Veronica M. Amado a a Laboratory of Respiratory Physiology, Universidade de Brasília, Brasília – DF, Brazil b Division of Gastroenterology, Hospital de Base do Distrito Federal, Brasília – DF, Brazil c Division of Pathology, Hospital Universitário de Brasília, Brasília – DF, Brazil a r t i c l e i n f o Article history: Accepted 4 October 2011 Keywords: Respiratory mechanics Airway remodeling Pulmonary vascular remodeling Morphometry Inflammation Common bile duct ligation a b s t r a c t Intrapulmonary vasodilation is a hallmark of the hepatopulmonary syndrome (HPS). However, its effects on respiratory mechanical properties and lung morphology are unknown. To determine these effects, 28 rats were randomly divided to control and experimental HPS groups (eHPS). The spontaneous breath- ing pattern, gas exchange, respiratory system mechanical properties, and lung and liver morphology of the rats were evaluated. Tidal volume, minute ventilation and mean inspiratory flow were signifi- cantly reduced in the eHPS group. Chest wall pressure dissipation against the resistive and viscoelastic components and elastic elastance were increased in the eHPS group. The lung resistive pressure dis- sipation was lower but the viscoelastic pressure was higher in the eHPS group. The airway volume proportion of collagen and elastic fibers was increased in the eHPS animals (16% and 51.7%; P < 0.05 and P < 0.001, respectively). The proportion of collagen volume in the vasculature increased 29% in the eHPS animals (P < 0.01). HPS presents with respiratory system mechanical disarray as well as airway and vascular remodeling. © 2011 Elsevier B.V. All rights reserved. 1. Introduction The hepatopulmonary syndrome (HPS) is a condition charac- terized by pulmonary vascular dilation, arterial hypoxemia and liver disease (Rodríguez-Roisin and Krowka, 2008). The preva- lence of HPS in patients with cirrhosis is approximately 10 to 20%, which increases morbidity and mortality (Fallon and Abrams, 2000; Schenk et al., 2003). The pathogenesis of this syndrome is still not completely understood, but some pulmonary vasodilators such as nitric oxide (NO) may be an important contributor to pulmonary vasodilation (Nunes et al., 2001). Current evidences suggest that liver disease leads to pulmonary complications (Fallon and Abrams, 2000). It has been demonstrated that hepatic production of cytokines (Zhang et al., 2003) and growth factors (Zhang et al., 2009) are involved in the pathophysiology of HPS and portopulmonary hypertension suggesting a liver-induced lung injury (Spagnolo et al., 2010). It is well documented in clinical (Freezer et al., 1993; Griifin et al., 1972) and experimental studies (Peták et al., 2002, 2004, ∗ Corresponding author at: Laboratório de Fisiologia Respiratória, Faculdade de Medicina, Campus Universitário Darcy Ribeiro, Universidade de Brasília, Brasília – DF 70910-900, Brazil. Tel.: +55 61 3032 7640; fax: +55 61 3307 2267. E-mail address: camelo@me.com (C.A. Melo-Silva). 2009) that lung mechanical properties, parenchyma stability and lung structure are profoundly influenced by pulmonary hemo- dynamics (primarily pulmonary capillary pressure). It has been established that elevated and very low capillary pressures increase lung impedance and modify alveolar architecture and mechanical properties (Silva et al., 2010; West, 2000). The association between high intrapulmonary vascular flow and low pulmonary vascular resistance is well established in the lit- erature on HPS respiratory pathophysiology (Palma and Fallon, 2006). However, its impact on pulmonary mechanical properties and on lung tissue structure as well as composition requires fur- ther elucidation. In the present study, we evaluated respiratory system mechanical properties as well as lung parenchyma mor- phology, the pulmonary airways and the vasculature in a rat model of HPS. 2. Materials and methods Our institutional animal care committee approved this study. All animals received human care in compliance with the “Prin- ciples of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences, USA. 1569-9048/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2011.10.001