Bubble and macroaggregate methods differ in detection of blood flow through intrapulmonary arteriovenous anastomoses in upright and supine hypoxia in humans

Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) increases in healthy humans breathing hypoxic gas and is potentially dependent on body position. Previous work in subjects breathing room air has shown an effect of body position when Q̇IPAVA is detected with transthoracic saline contrast echocardiography (TTSCE). However, the potential effect of body position on Q̇IPAVA has not been investigated when subjects are breathing hypoxic gas or with a technique capable of quantifying Q̇IPAVA. Thus the purpose of this study was to quantify the effect of body position on Q̇IPAVA when breathing normoxic and hypoxic gas at rest. We studied Q̇IPAVA with TTSCE and quantified Q̇IPAVA with filtered technetium-99m-labeled macroaggregates of albumin (99mTc-MAA) in seven healthy men breathing normoxic and hypoxic (12% O2) gas at rest while supine and upright. On the basis of previous work using TTSCE, we hypothesized that the quantified Q̇IPAVA would be greatest with hypoxia in the supine position. We found that Q̇IPAVA quantified with 99mTc-MAA significantly increased while subjects breathed hypoxic gas in both supine and upright body positions (ΔQ̇IPAVA = 0.7 ± 0.4 vs. 2.5 ± 1.1% of cardiac output, respectively). Q̇IPAVA detected with TTSCE increased from normoxia in supine hypoxia but not in upright hypoxia (median hypoxia bubble score of 2 vs. 0, respectively). Surprisingly, Q̇IPAVA magnitude was greatest in upright hypoxia, when Q̇IPAVA was undetectable with TTSCE. These findings suggest that the relationship between TTSCE and 99mTc-MAA is more complex than previously appreciated, perhaps because of the different physical properties of bubbles and MAA in solution. NEW & NOTEWORTHY Using saline contrast bubbles and radiolabeled macroaggregrates (MAA), we detected and quantified, respectively, hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) in supine and upright body positions in healthy men. Upright hypoxia resulted in the largest magnitude of Q̇IPAVA quantified with MAA but the lowest Q̇IPAVA detected with saline contrast bubbles. These surprising results suggest that the differences in physical properties between saline contrast bubbles and MAA in blood may affect their behavior in vivo.