title: Inhaled nitric oxide alters the distribution of blood flow in the healthy human lung, suggesting active hypoxic pulmonary vasoconstriction in normoxia.
abstract: Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2 ) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2 × iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2 , there were statistically significant increases in Global Fluctuation Dispersion, (a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2 dependent (P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia (P = 0.007) and normoxia (P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Amran K
authors.initials: AK
authors.lastname: Asadi
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Rui Carlos
authors.initials: RC
authors.lastname: Sá
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; and.
authors.forename: Nick H
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Theilmann
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; and Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Hopkins
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Buxton
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California; and Department of Radiology, University of California, San Diego, La Jolla, California kprisk@ucsd.edu.
authors.forename: G Kim
authors.initials: GK
authors.lastname: Prisk
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D010477:Perfusion / Q000379:methods; D011652:Pulmonary Circulation / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013113:Spin Labels; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D013113:Spin Labels; D009569:Nitric Oxide
keywords: MRI; arterial spin labeling; hypoxic pulmonary vasoconstriction; nitric oxide; pulmonary blood flow