Pulmonary capillary endothelial metabolic function in chronic thromboembolic pulmonary hypertension

Summary.  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.