Clinical Consideration for Techniques to Detect and Quantify Blood Flow through Intrapulmonary Arteriovenous Anastomoses: Lessons from Physiological Studies

Abstract

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 (QIPAVA) 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 QIPAVA include allowing emboli to reach the systemic circulation and providing a source of shunt. Studying QIPAVA is an important area of research and as the suggested roles become better established, detecting and quantifying QIPAVA may become significantly more important in the clinic. Several techniques that can be used to quantify and/or detect QIPAVA 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 QIPAVA in animals, ex vivo lungs, and healthy humans has established conditions when QIPAVA is present, such as during exercise or with arterial hypoxemia and conditions when QIPAVA 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.

Screening children for pulmonary arteriovenous malformations: Evaluation of 18 years of experience

“…Literature clearly indicates that transthoracic contrast echocardiogram (TTCE) is optimal for detecting PAVMs in adults and probably also in the pediatric HHT population, as some studies have shown . It should also be noted however, that this literature does not take into account non PAVM causes of a right‐to‐left shunt . Though very rare, there is a potential risk of ischemic stroke as a complication of TTCEs in patients with significant shunt …”

Identification of candidates for PFO closure in the echocardiography laboratory

“…In addition to detection of PAVS with an increased frequency in cCVA, it appears that PAVS is “dynamic”. That is, PAVS may occur with increased severity and frequency during “hypoxic” states or during exercise . It is the presence of a previously undetected PAVS that has been noted to be a causative agent for persistent detection of a right‐to‐left shunt after device closure of a PFO …”

Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients

“…This filtering role can be compromised, however, by the presence of both intrapulmonary (eg, intrapulmonary arteriovenous anastomoses, IPAVA) and intracardiac (eg, patent foramen ovale, PFO) right‐to‐left shunts . The presence of these pathways does not guarantee that a patient will have a stroke or transient ischemic attack because there are large numbers of otherwise healthy humans, which have either blood flow through IPAVA (~30%) and/or PFO (25%–40%) under resting conditions . Nevertheless, with these pathways present and the propensity for emboli formation in individuals who may be prothrombotic, the opportunity exists for emboli of venous origin to bypass the pulmonary microcirculation.…”

“…1,2 The presence of these pathways does not guarantee that a patient will have a stroke or transient ischemic attack because there are large numbers of otherwise healthy humans, which have either blood flow through IPAVA (~30%) and/or PFO (25%-40%) under resting conditions. [3][4][5][6][7] Nevertheless, with these pathways present and the propensity for emboli formation in individuals who may be prothrombotic, the opportunity exists for emboli of venous origin to bypass the pulmonary microcirculation. Therefore, IPAVA and PFO may contribute to the etiology of stroke and TIA in some patients.…”