Pulmonary arterial hypertension (PAH) reduces exercise capacity. Progressive loss of perfused pulmonary arterioles with resulting loss of downstream functional capillary surface area (FCSA) causes increased pulmonary vascular resistance. Humans normally recruit unused FCSA during exercise, and pulmonary artery pressure (PAP) rises minimally. PAH patients may have severe reductions in FCSA at rest. We hypothesized that, in patients with PAH, failure to recruit FCSA during exercise might correlate with worse exercise-induced pulmonary hypertension. By measuring the first-pass transpulmonary metabolism of 3H-benzoyl-Phe-Ala-Pro (BPAP) as it interacts with the endothelial-bound angiotensin converting ectoenzyme, we are able to determine FCSA in humans. BPAP is injected into the right atrium via a thermodilution catheter and systemic arterial effluent is collected. The procedure is performed prior to and at peak tolerated supine bicycle exercise. We provide the example of two patients with scleroderma and NYHA class 3 yspnea. Patient 1 had mPAP 24 mm HG, cardiac output (CO) 4.8 L/min, and patient 2 had mPAP 32, and CO 4.3. Both exercised to 30 Watts. At peak exercise, patient 1 had mPAP 32 and CO 9.25, versus mPAP 52 and CO 9.03 for patient 2. However, FCSA/BSA for patient 1 rose from 2522 to 4277 mL/min/m2 whereas, in patient 2, FCSA/BSA only changed from 1211 to 1862. Despite similar workloads and cardiac output increases, the patient with greater exercise-induced PH had a markedly decreased FCSA/BSA at rest and could not increase meaningful FCSA/BSA on exercise. Exercise-induced PH may represent a failure to recruit pulmonary microvasculature, in an already restricted vascular bed.
