Reply to Bogaard et al.: Emphysema Is—at the Most—Only a Mild Phenotype in the Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension

Abstract

volume, in the absence of a pleural leakage. In summary, based on a search of the literature and on the analysis of our own SuHx rat studies (Table 1 and Figure 1), we cannot confirm the presence of moderate or severe emphysema in the established SuHx rat model of PAH. At most, there may be mild enlargement of intraalveolar spaces depending on rat strain, number of SU5146 doses, and timing of lung harvest. In contrast, there is ample evidence that repetitive SU5416 injections alone (i.e., blockade of VEGFR2 and other kinases), in the absence of hypoxia, can produce an emphysema-like lung phenotype, but the latter mainly occurs in younger rats in which postnatal lung development may still be ongoing (3). Our data provide evidence that the SuHx rat model, when yielding RVSP consistently .60 mm Hg, using adequate controls and standardized lung inflation, is currently one of the best rodent models for studying PAH and pulmonary vascular disease. The SuHx rat model allows the study of the mechanisms of cardiovascular remodeling, vessel loss and RV failure, and lacks a biologically relevant emphysemalike lung phenotype. n