Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension

Primary pulmonary hypertension (PPH) is associated with a spectrum of structural changes in the pulmonary arteries: increased medial thickness, eccentric and concentric intimal thickening, obliteration and recanalization of arteries, and appearance of plexiform and dilatation lesions. The purpose of the present study was to further characterize these structural changes with particular emphasis on arterial adventitial thickness and alterations in the walls of the pulmonary veins. In addition, to determine whether the characteristic structural changes of PPH were size related, each was related to external diameter. With quantitative techniques, the pulmonary vasculature of 19 patients with PPH and 7 controls was examined by light microscopy. In all 19 patients, we found a striking increase in adventitial, as well as intimal and medial, thickness in arteries of all sizes when compared with controls (P < 0.05). In addition, we found intimal and adventitial thickening of pulmonary veins < 250 mu in diameter in approximately half of the PPH cases (P < 0.05). The frequency of arterial obliteration, concentric intimal thickening, and recanalization was 16, 18, and 11 of 19 cases, respectively. These changes were most prevalent in arteries less than 200 mu in diameter whereas eccentric intimal thickening and plexiform lesions occurred in 15 and 6 of the patients, respectively, and were most widespread in arteries > 200 mu. We conclude that remodeling of the pulmonary vasculature in PPH routinely includes thickening of the arterial adventitia and frequently also includes changes in the walls of the pulmonary veins. The finding that recanalization occurs predominantly in the smaller arteries whereas eccentric intimal thickening occurs mainly in the larger ones suggests that recanalization should not be considered a consequence of thromboemboli but may also occur at sites of more fibrotic intimal change.