New Findings r What is the central question of this study?Compared with exercise while breathing room air, blood flow through intrapulmonary arteriovenous anastomoses during exercise while breathing 100% O 2 is prevented/reduced, presumably due to vasoconstriction of these vessels. We sought to investigate the effect of sildenafil, nifedipine and acetazolamide, which are known modulators of pulmonary vascular tone, on the hyperoxia-induced reduction in blood flow through intrapulmonary arteriovenous anastomoses during exercise. r What is the main finding and its importance?We show that,independently, sildenafil, nifedipine and acetazolamide do not prevent the hyperoxia-induced reduction in blood flow through intrapulmonary arteriovenous anastomoses during exercise. These data provide the first insight into the regulation of intrapulmonary arteriovenous anastomoses during exercise while breathing 100% O 2 .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% O 2 , 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 (Q 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) onQ IPAVA at rest and during cycle ergometer exercise at 50, 100, 150, 200 and 250 W, while breathing room air (normoxia) and 100% O 2 (hyperoxia). Transthoracic saline contrast echocardiography and a 0-5 bubble scoring system were used to detect and assessQ 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 onQ IPAVA ; specifically, bubble scores were the same
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