Correspondence
Signaling Molecules in Pulmonary Hypertension
N Engl J Med 2003; 348:2151May 22, 2003
- Article
To the Editor:
In their thought-provoking article, Du et al. (Feb. 6 issue)1 report a striking correlation between the level of angiopoietin-1 in the lung and the degree of pulmonary vascular resistance in patients with pulmonary hypertension. The fact that these patients had various types of disease makes these findings difficult to interpret, especially since the majority of patients had chronic thromboembolic pulmonary hypertension and underwent thromboendarterectomy.
In contrast to other types of pulmonary hypertension, increased pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension is due mostly to the obliteration of proximal vessels. In fact, the absence of major involvement of the peripheral vasculature is a prerequisite for successful thromboendarterectomy. However, the histologic examinations as well as the RNA and protein analyses in the study involved mostly peripheral vessels (100 to 1000 μm in diameter) — that is, vessels that should not be grossly affected by vascular remodeling.
1 ReferencesMarius M. Hoeper, M.D.
Hannover Medical School, 30627 Hannover, Germany
hoeper.marius@mh-hannover. de Author/Editor Response
The proportions of specimens studied (i.e., specimens from patients with thromboembolic disease, primary pulmonary hypertension, Eisenmenger's syndrome, or collagen vascular disease) reflect the proportions of these diseases among cases treated by ourselves and the other cardiothoracic surgeons in our group. For example, last year at our institution, one heart–lung transplantation was performed for the treatment of Eisenmenger's syndrome, whereas more than 100 pulmonary endarterectomies were performed for the treatment of chronic thromboembolic disease. Specimen availability was a limitation in this study, as it would be in any study addressing multiple forms of pulmonary hypertension, since surgical therapy is rarely used for some causes of this disease.
Having performed more than 1400 pulmonary endarterectomies at our institution since 1990, we have come to realize that thromboembolic pulmonary hypertension represents a spectrum of vascular disease.1 In the proximal pulmonary arterial tree, unresolved pulmonary emboli cause vascular obstruction by two mechanisms: first, by directly occluding the vessel lumen, and second, by inducing secondary endothelial changes comprising cellular hyperplasia, webbing, and incomplete clot remodeling. In addition, in patients with chronic thromboembolism, the terminal pulmonary arterioles manifest, to varying degrees, a pathologic process similar to that seen in primary pulmonary hypertension, whereby these small vessels become excessively thickened by muscular hypertrophy and hyperplasia, leading eventually to occlusion. A spectrum of changes in large and small vessels is encountered when pulmonary endarterectomy is used for the treatment of chronic pulmonary hypertension. In analyzing more than 60 lung-biopsy specimens obtained from patients undergoing pulmonary endarterectomy in the past two years, we have always found that some degree of small-vessel vasculopathy accompanies larger-vessel thromboembolic vascular occlusion. In the future, experiments will be directed at determining whether arteriolar vascular changes occur in vessel beds that are the most or the least affected by proximal thromboembolic occlusion.
1 ReferencesPatricia A. Thistlethwaite, M.D., Ph.D.
Stuart W. Jamieson, M.B., F.R.C.S.
University of California, San Diego, San Diego, CA 92103-8892
pthistlethwaite@ucsd.edu 1
Thistlethwaite PA ,Mo M ,Madani MM , et al. Operative classification of thromboembolic disease determines outcome after pulmonary endarterectomy. J Thorac Cardiovasc Surg 2002;124:1203-1211
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- Citing Articles (1)
Citing Articles
1
(2007) Determination of Methylmercury in Biological Samples Using Dithizone Extraction Method Followed by Purge & Trap GC-MS. Bulletin of the Korean Chemical Society 28:12, 2293-2298
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