Clinical consideration for techniques to detect and quantify blood flow through intrapulmonary arteriovenous anastomoses: Lessons from physiological studies

Intrapulmonary arteriovenous anastomoses (IPAVA) are large diameter (>50 μm) vascular conduits, present in >95% of healthy humans. Because IPAVA are large diameter pathways that allow blood flow to bypass the pulmonary capillary network, blood flow through IPAVA (Q_IPAVA) can permit the transpulmonary passage of particles larger than pulmonary capillaries. IPAVA have been known to exist for over 50 years, but their physiological and clinical significance are still being established; although, currently suggested roles for Q_IPAVA include allowing emboli to reach the systemic circulation and providing a source of shunt. Studying Q_IPAVA is an important area of research and as the suggested roles become better established, detecting and quantifying Q_IPAVA may become significantly more important in the clinic. Several techniques that can be used to quantify and/or detect Q_IPAVA in animals, ex vivo human/animal lungs, and intact healthy humans; microspheres, radiolabeled macroaggregated albumin particles, and saline contrast echocardiography, are reviewed with limitations and advantages to each. The current body of literature using these techniques to study Q_IPAVA in animals, ex vivo lungs, and healthy humans has established conditions when Q_IPAVA is present, such as during exercise or with arterial hypoxemia and conditions when Q_IPAVA is absent, such as at rest or during exercise breathing 100% O₂. Many of these physiological studies have direct application to patient populations and we discuss each of these findings in the context of their potential to influence the clinical utility, and interpretation, of the results from these techniques highlighted in this review.