A rabbit model of pulmonary hypertension induced by the synthetic platelet-activating factor acetylglyceryl ether phosphorylcholine

Abstract

Development of effective treatment for human pulmonary hypertension (PHT) has been hampered by an incomplete understanding of its pathogenesis. We present a rabbit model of PHT based on platelet-activating factor (PAF), a potent phospholipid autacoid synthesized by a variety of mammalian cells. PAF was intravenously infused into rabbits for 4 wk. After the infusion, rabbits underwent pulmonary arterial catheterization for hemodynamic evaluation, and lung tissue was morphometrically analyzed for changes in cross-sectional areas of intima and media, and alteration in number of small pulmonary arteries. The heart was evaluated by the method of Fulton for right ventricular hypertrophy. Mean pulmonary arterial pressure was 20 +/- 2 mm Hg in PAF-treated rabbits compared with 12 +/- 1 mm Hg in vehicle-treated control rabbits. PAF induced a trend toward loss of small muscular pulmonary arteries, measuring 50 to 200 microns in diameter, and right ventricular hypertrophy. There was a decrease in circumference of the internal elastic lamina in vessels accompanying alveolar ducts and in alveolar walls, and a relative increase in the intimal cross-sectional area of these vessels. These lesions were associated with a trend toward medial hypertrophy. No increase in lung water was found. Pressure changes occurred in the absence of alterations in hematocrit and arterial partial pressure of oxygen. We conclude that chronic intravenous infusion of PAF, a naturally synthesized substance, into rabbits provides a potentially useful model for the study of vascular changes associated with PHT.