Repeated pulmonary thromboembolism in rabbits.

Ten rabbits received 24 to 76 intravenous injections of finely divided thrombi prepared by a modification of Chandler's apparatus. Eight rabbits were killed soon after the last injection (group A) and two rabbits were allowed to survive for 4 months after the last introduction of thrombi (group B). Ten rabbits received repeated saline injections only, and six animals underwent no manipulation whatever. Six test rabbits and six control rabbits underwent catheterization of the pulmonary artery. The pulmonary arteries of each lung received injections of radiopaque material and were x-rayed; multiple blocks were selected from each lobe of each lung, cut, and stained with Weigert's elastic Van Gieson's stain, which permitted measurement of arterial medial thickness. Sections were also stained with hematoxylin and eosin and Martius scarlet blue. The results of catheterization showed that only mild pulmonary hypertension had been induced. Histologically, thromboemboli had become incorporated into the wall of the arteries. Concentric intimal thickening included an "onionskin" arrangement and was more prevalent than eccentric configuration. Medial hypertrophy of almost all vessels was found. The onionskin arrangement in an occasional precapillary vessel was also encountered. More severe histologic grades of pulmonary hypertension were not seen. The two group B animals showed recent thrombi, which suggested that once intimal thickening had occurred the process of fresh thrombotic superimposition continues, resulting in progression of the lesions. The experimental findings were compared with 13 patients (thromboembolic pulmonary hypertension (eight) and primary pulmonary hypertension (five)) and with 181 patients reported in the literature. Features such as the onionskin type of intimal thickening in muscular arteries and precapillary vessels have been suggested as points of distinction between these two conditions. These features have been reproduced in these experiments. Despite the fact that more severe histologic grades of pulmonary hypertension were not produced, it is suggested that these experiments lend support to the concept that primary pulmonary hypertension may have a thromboembolic etiology in at least some patients.