Pulmonary membrane diffusing capacity and capillary blood volume measured during exercise from nitric oxide uptake

Study objectives: To validate lung diffusing capacity for nitric oxide (DLNO) as an index of conductance of the alveolar-capillary membrane during exercise, we compared DLNO to lung diffusing capacity for carbon monoxide (DLCO) and pulmonary membrane diffusing capacity for carbon monoxide (DMCO), and compared pulmonary capillary blood volume (Vc) calculated by two methods. Setting and participants: The study was performed at a university medical center involving 12 nonsmoking healthy volunteers (age range, 23 to 79 years). DLCO, DLNO, cardiac output (Q̇c), and lung volume were measured simultaneously at rest and during graded ergometer exercise by a rebreathing technique. Pulmonary membrane diffusing capacity and Vc were compared by (1) the classic technique of Roughton and Forster from DLCO measured at two alveolar oxygen tension (PAO₂) levels, and (2) from DLNO and DLCO assuming negligible erythrocyte resistance to nitric oxide (NO) uptake, ie, DLNO approximately equal to pulmonary membrane diffusing capacity for nitric oxide. Results: In all subjects, DLNO increased linearly from rest to exercise; age, Q̇c, and lung volume were the major determinants of DLNO by stepwise regression analysis. The DLNO/DLCO ratio averaged 3.98 ± 0.38 (± SD) and the DLNO/DMCO ratio averaged 2.49 ± 0.28 irrespective of exercise intensity. Changing PAO₂ did not alter DLNO. Brief exposure to 40 ppm of inhaled NO during 16 s of rebreathing did not alter either DLCO or Q̇c. Estimates of pulmonary membrane diffusing capacity and Vc by the two methods showed a strong correlation. Conclusion: Results support DLNO as a direct measure of pulmonary membrane diffusing capacity, allowing the estimation of Vc in a single rebreathing maneuver during exercise. The DLNO-DLCO rebreathing technique can be applied clinically in the investigation of pulmonary microvascular regulation.