CTEPH capillary dysfunction caused by thrombus

15 August 2008

MedWire News: Chronic thromboembolic pulmonary hypertension (CTEPH) causes a reduction in the functional capillary surface area (FCSA) of the lungs, researchers have found.

The team demonstrates in the Journal of Thrombosis and Haemostasis that the reduction in FCSA is probably caused by thrombus in upstream blood vessels rather than a reduction in the capillaries' metabolic capacity.

David Langleben (Jewish General Hospital, Montreal, Quebec, Canada) and colleagues assessed the impact of CTEPH on pulmonary endothelial metabolism in 13 patients with CTEPH and 23 control patients with coronary artery disease.

The team measured pulmonary capillary endothelium-bound angiotensin converting enzyme (PCEB-ACE) activity using a hemodynamically inactive radiolabelled tripeptide.

The tripeptide, which is metabolized by ACE, was injected into the right atrium via a pulmonary artery catheter and transpulmonary effluent blood was collected using a catheter in the femoral artery.

Analysis showed that single-pass transpulmonary per cent metabolism (%M) was similar in CTEPH patients and controls (71.6% vs 74.7%), as was substrate hydrolysis of the ACE synthetic substrate (1.47 vs 1.51).

However, patients with CTEPH had significantly lower FCSA normalized by body surface area compared with controls, at 1530 versus 2948 ml/min/m2.

"Because %M and hydrolysis are preserved, this points to a reduction in FCSA rather than reduced ACE activity on the pulmonary capillary endothelial cell," Langleben et al write.

"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."

They conclude: "One might expect this abnormality to correct after pulmonary thromboendarterectomy, but this hypothesis must be confirmed in future clinical studies with repeat measurements of PCEB-ACE activity before and after surgery."

J Thromb Haemost 2008; 6: 1275-1280