title: Sildenafil, nifedipine and acetazolamide do not allow for blood flow through intrapulmonary arteriovenous anastomoses during exercise while breathing 100% oxygen.
abstract: Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) is known to increase in healthy humans during exercise while breathing room air, but is prevented or significantly reduced during exercise while breathing 100% O2, potentially due to vasoconstriction of IPAVAs. Thus, pharmacological interventions that target known pathways regulating the cardiopulmonary circulation may be able to prevent the hyperoxia-induced reduction in IPAVA blood flow (Q̇ IPAVA ) during exercise. In nine healthy human subjects, we investigated the effects of sildenafil (100 mg p.o.), nifedipine (20 mg p.o.) and acetazolamide (250 mg p.o. three times a day for 3 days) on Q̇ IPAVA at rest and during cycle ergometer exercise at 50, 100, 150, 200 and 250 W, while breathing room air (normoxia) and 100% O2 (hyperoxia). Transthoracic saline contrast echocardiography and a 0-5 bubble scoring system were used to detect and assess Q̇ IPAVA qualitatively; ultrasound was used to assess the blood flow velocity oftricuspid regurgitation and the left ventricular outflow tract blood flow to calculate pulmonary artery systolic pressure (PASP) and cardiac output, respectively. Without drugs, bubble scores increased significantly to ≥2 at 150 W in normoxia and to ≤2 at 200 W in hyperoxia. Only nifedipine consistently increased cardiac output at rest and during low-intensity exercise in normoxia and hyperoxia. However, there was no detectable effect of any drug on Q̇ IPAVA ; specifically, bubble scores were the same during exercise in either normoxia or hyperoxia. Accordingly, the reduction in Q̇ IPAVA during exercise while breathing 100% O2 is likely not to be due to the independent pharmacological mechanisms of action associated with sildenafil, nifedipine or acetazolamide.
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, OR, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Elliott
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, OR, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Friedman
authors.affiliation: Oregon Heart & Vascular Institute, Springfield, OR, USA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Futral
authors.affiliation: Oregon Heart & Vascular Institute, Springfield, OR, USA.
authors.forename: Randall D
authors.initials: RD
authors.lastname: Goodman
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, OR, USA lovering@uoregon.edu.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lovering
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000328:Adult; D001163:Arteriovenous Anastomosis / Q000187:drug effects* / Q000502:physiology; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D012119:Respiration; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D009543:Nifedipine; D000086:Acetazolamide; D010100:Oxygen