Epinephrine opens intrapulmonary arteriovenous anastomoses in healthy humans at rest

Abstract

During exercise or while breathing hypoxic gas mixtures large diameter intrapulmonary arteriovenous anastomoses (IPAVA) open and can be detected with saline contrast echocardiography (SCE). The mechanisms regulating these vessels remain unknown, but both of these conditions activate the sympathetic nervous system and increase plasma catecholamine concentrations. We hypothesized that exogenously increasing the plasma epinephrine concentration would open IPAVA. Using SCE, we studied 5 subjects at rest, before and after continuous infusions of epinephrine at 20, 40, 80, 160, and 320 ng/kg/min for 3 min each. Cardiac output (Q) and pulmonary artery systolic pressure (PASP) were measured using ultrasound. Bubble scores (0–5) increased in a dose‐dependent fashion in all subjects to a max score ranging from 2–4. Q and PASP doubled at the highest infusion rate. After a 30 min break, epinephrine infusions were repeated while subjects breathed 100% O2 and bubble scores did not increase despite similar increases in cardiac output and PASP. These data demonstrate that during exercise or when breathing hypoxic gas mixtures the sympathetically‐mediated release of epinephrine may directly open IPAVA independent of changes in cardiac output or PASP. Mechanisms responsible for hyperoxia‐mediated closure remain elusive.Support: Eugene Evonuk Graduate Fellowship in Exercise & Environmental Physiology

A Mathematical Model for the Quantification of Pulmonary and Intrapulmonary Arteriovenous Anastomoses Blood Flow

“…Therefore, as verified by various authors through the TTSCE and 99mTc-MAA techniques mentioned above (14,15,17,19,20,21,22,24,25), in this study, the presence of IPAVA was confirmed in healthy humans in conditions of both normoxia (during exercise) and hypoxia (at rest and during exercise). Unfortunately, as already pointed out, in normoxia at rest, the t measure was underestimated; therefore, it was not possible to verify, in this study, if IPAVA are open during this condition, although it should be emphasized that various authors (19,20) have verified that in healthy humans, in normoxia at rest, IPAVA are closed, but only in the vast majority of cases and not in all subjects (26).…”

“…However, both techniques made it possible to detect blood flow through IPAVA in healthy humans in normoxia during exercise (14,20) and, at rest and during exercise, in hypoxia (19,15). Furthermore, the simultaneous use of the two techniques, TTSCE and 99mTc-MAA, led to consistent data (24).…”

“…• 99mTc-MAA allows the calculation of the percentage of shunts with respect to the cardiac output, which flows in IPAVA but presents technical difficulties (preliminary selection of the MAA size) and possible errors in the subjective determination of the lung region of interest (ROI). Furthermore, another source of error in quantifying IPAVA is the time, since any delay between injection of labeled MAA and scanning will increase the possibility of overestimating IPAVA (24,25).…”

“…In particular, in healthy subjects, IPAVA are typically closed or poorly perfused under resting conditions but can open during moderate to high intensity exercise in normoxia (14,15,25). In hypoxia, these pathways are perfused under resting conditions depending on the severity of hypoxemia (19,20), and there is greater blood flow through these pathways with exercise and hypoxia (14,15,17,20,21,22,24,25). Therefore, IPAVA are dynamic pulmonary pathways through which blood flows and that fraction of pulmonary blood flow is variably present depending on the conditions to which the subjects are exposed.…”

“…Currently shunts are approximately estimated by techniques such as echocardiographic method (transthoracic saline contrast echocardiography -TTSCE) (14,15,17,25) and with technetium-99m labeled macroaggregated albumin (99mTc-MAA) (21,22,23,25), but both techniques have limitations (24). While the measurement of cardiac output is currently carried out through various methods, such as indicator dilution techniques, the Fick method, arterial pulse contour analysis, ultrasound, and bioimpedance (9), and specifically during exercise, cardiac output can be measured by open-circuit acetylene uptake (10,11).…”