Chest
Volume 138, Issue 5, November 2010, Pages 1234-1239
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Selected Reports
Long-term Effects of Epoprostenol on the Pulmonary Vasculature in Idiopathic Pulmonary Arterial Hypertension

https://doi.org/10.1378/chest.09-2815Get rights and content

The current treatment of pulmonary arterial hypertension (PAH) uses vasodilator drugs. Although they improve symptoms associated with PAH, their chronic effects on the pulmonary vasculature and the right ventricle (RV) in humans remain unknown. We report the autopsy findings from a patient with idiopathic PAH treated with epoprostenol successfully for 18 years. The patient died of colon cancer. The pulmonary vasculature surprisingly showed extensive changes of a proliferative vasculopathy. Immunohistochemical studies confirmed ongoing cellular proliferation. Studies of the RV demonstrated concentric hypertrophy with seemingly preserved contractility. The myocardium shifted to glycolytic metabolism. Although the long-term use of epoprostenol contributed to the patient's increased survival, it did not prevent progression of the underlying vascular disease. Remarkably, the RV was able to sustain a normal cardiac output in the face of advanced vascular pathology. The mechanisms by which the RV adapts to chronic PAH need further study.

Section snippets

Case Report

The patient was a 53-year-old woman who presented with unexplained dyspnea at age 31 in 1987. A thorough evaluation revealed IPAH as the etiology. She had an elevated pulmonary arterial pressure and pulmonary vascular resistance at cardiac catheterization (Table 1) but was found to be nonvasoreactive to vasodilator challenge and was managed conservatively. In 1991, the patient entered the pivotal clinical trial of epoprostenol for IPAH3 and was randomized to active therapy, which she remained

Histopathologic Findings of the Pulmonary Circulation

The small- to medium-sized pulmonary arteries demonstrated severe muscular hypertrophy and intimal fibrosis with occasional complete occlusion of the lumen. There were frequent plexiform lesions adjacent to arterial branch points, most of which had associated vascular dilatation (Fig 1). Immunostaining revealed the presence of occasional small platelet thrombi and a mild inflammatory infiltrate in the plexiform lesions consisting of CD4+ and CD8+ T cells, CD68+ macrophages, and rare CD20+ B

Discussion

There are several treatments approved specifically for PAH.1 Although all are vasodilators, each class of treatment has been demonstrated to have some degree of antiproliferative effect on vascular smooth muscle cells either in vitro or in animal models of PAH.9, 10, 11 Although clinical trials have demonstrated that they have only modest effects on lowering the pulmonary arterial pressure, it has been proposed that the long-term use of these therapies may reverse some of the pulmonary vascular

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Gomberg-Maitland has received research grant support from Actelion, Gilead, Lilly/Icos, Novartis, Pfizer, and United Therapeutics and has served as a consultant for Biomarin, Gilead, Medtronic, Millenium, and Pfizer. She does not do any promotional speaking and has received honoraria from ABcomm and HealthmattersCME for continuing medical education-related events. She has a patent

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    Funding/Support: This work is supported by National Institutes of Health [grants RO1-HL071115 and 1RC1HL099462-01], the American Heart Association, and the Roche Foundation for Anemia Research (to Dr Archer).

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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