Pulmonary capillary endothelial metabolic function in chronic thromboembolic pulmonary hypertension

J Thromb Haemost. 2008 Aug;6(8):1275-80. doi: 10.1111/j.1538-7836.2008.03046.x. Epub 2008 Jun 4.

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) causes physical plugging of large pulmonary arteries as well as a distal micro-vasculopathy. Pulmonary endothelium is an active metabolic tissue in normal humans. The effects of CTEPH on pulmonary endothelial metabolism are unknown.

Objectives: We studied pulmonary capillary endothelium-bound angiotensin converting enzyme (ACE) activity as an index of endothelial metabolism in patients with CTEPH.

Patients/methods: We measured single-pass transpulmonary per cent metabolism (%M) and hydrolysis of an ACE synthetic substrate and calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), in 13 patients with CTEPH and 23 controls.

Results: Mean %M for CTEPH (71.6 +/- 4.0% SE) was similar to controls (74.7 +/- 2.7%). Substrate hydrolysis (v) was similar for CTEPH (1.47 +/- 0.22) and controls (1.51 +/- 0.11). However, FCSA/BSA was reduced (P < 0.01) for CTEPH (1530 +/- 218 mL min(-1)*m(-2)) as compared with controls (2948 +/- 245).

Conclusions: The metabolically functional pulmonary capillary bed is reduced in CTEPH. However, because %M and hydrolysis are preserved, this points to a reduction in functional capillary surface area rather than reduced ACE activity on the pulmonary capillary endothelial cell. The reduction in functional capillary surface area may just be a result of decreased capillary recruitment because of upstream vascular plugging by chronic organized thrombus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillaries / metabolism
  • Capillaries / pathology
  • Case-Control Studies
  • Chronic Disease
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / pathology
  • Kinetics
  • Lung / blood supply*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / metabolism
  • Thromboembolism / complications
  • Thromboembolism / metabolism*
  • Thromboembolism / pathology

Substances

  • Peptidyl-Dipeptidase A