Morphological and immunohistochemical characterization of pulmonary vascular lesions in patients with pulmonary hypertension associated with left heart failure: clinical and hemodynamical correlations

Abstract

Patients with left cardiac dysfunction due to primary myocardial or valvar involvement may develop, especially in the advanced stages of the disease, passive pulmonary hypertension (PH). It is well recognized that the development of PH in these patients is associated with poor prognosis and also that it may impact on the indication and evolution after heart transplantation. However, data from literature about its incidence, physiopathology and treatment are lacking. Objectives: in patients with PH associated with left heart failure, characterize and quantify the morphological lesions of the pulmonary vasculature (veins, venules, resistance and muscular arteries) concerning collagen deposition in their walls and the expression of the endotelin-1 (ET1) and phosphodiesterase-5 (PDE5); correlate the above results with those obtained from the hemodynamic evaluation. Methodology: 20 patients with left heart failure and listed for heart transplantation who died before, or up 30 days after the procedure were selected. The presence of hemodynamic data for pulmonary artery pressure measurements, as part of the assessment for selection to cardiac transplantation, and collected within 6 months before death, was considered an inclusion criterion in our study. Besides that, all selected patients were subjected to autopsy at the Laboratory of Pathology-InCor/University of São Paulo Medical School. The obtained pulmonary tissue was fixed in 10% formalin solution and after conventional histological processing, sectioned at 5 micrometers for histological analysis. The Miller and Sirius red staining methods were used respectively for the assessment of elastic and collagen fibers. Immunohistochemistry reactions will be performed for the labeling of ET1 and PDE5 receptors. All the arteries and veins present in the pulmonary tissue will be analyzed, provided that they do not present artifacts. The linear measurements (percentage of medial thickness of arteries and veins) and area fraction of collagen will be assessed by an imaging computerized analysis system. The area occupied by the adventitial layer and by intimal proliferative lesions of the arteries and veins will be calculated. The tissues subjected to imunohistochesmitry reactions will be also assessed quantitative and qualitatively. The morphometric data will be correlated with the results of hemodynamic evaluation. (AU)