Intra‐pulmonary arteriovenous anastomoses and pulmonary gas exchange: evaluation by microspheres, contrast echocardiography and inert gas elimination

Abstract

Key points Imaging techniques such as contrast echocardiography suggest that anatomical intra‐pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung. To evaluate this discrepancy, we compared anatomical shunt with 25‐µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET). Intra‐pulmonary shunt measured by 25‐µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt. A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. Abstract The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra‐pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right‐to‐left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25‐µm microspheres and compared the results to contrast echocardiography and MIGET‐determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg−1 min−1 i.v. dopamine, (3) 10 µg kg−1 min−1 i.v. dobutamine, and (4) following creation of an intra‐atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25‐µm microspheres recovered in systemic arterial blood. Ventilation–perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25‐µm microspheres. Across all conditions, anatomical shunt measured by 25‐µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%, P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60, P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22–48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25‐µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.

Precapillary pulmonary gas exchange is similar for oxygen and inert gases

“…However, this is not the case in the presence of intrapulmonary arteriovenous anastomoses, which have the potential to add deoxygenated blood to the systemic circulation. A companion paper documentes the transpulmonary passage of 25 µm microspheres in these same animals, confirming the presence of small functional pulmonary arteriovenous connections (Stickland et al ., ). The present study suggests that the amount of blood flowing through functional arteriovenous connections would be underestimated similarly by both MIGET and O 2 methods to evaluate shunt because similar relative amounts of inert gas and oxygen flowing through the intrapulmonary arteriovenous anastomoses would be lost by precapillary exchange.…”

“…In keeping with this, we did not detect any regions of low ratio (i.e. 0.005–0.1) under any condition in our companion study (Stickland et al ., ). Consequently, even if precapillary gas exchange results in apparently low regions, in the present study, the ratio of such regions is so low as to be indistinguishable from shunt.…”

“…As noted above, the present study was part of a larger project that also examined pulmonary gas exchange and arteriovenous shunt (Stickland et al, 2019). For completeness, there is some duplication with the companion paper (Stickland et al, 2019). A total of seven mixed-breed canines weighing between 19 and 25 kg were studied (Marshall BioResources, North Rose, NY, USA).…”

Measuring blood flow through intrapulmonary and intracardiac shunts: a technical labyrinth

“…Although the results from Stickland et al . () far from settle the debate on the contribution of cardiac and intrapulmonary shunt on the gas exchange deficits observed during exercise, they do highlight the limits of agitated saline contrast echocardiography in the detection of small shunts (<1%). Ultrasound contrast scoring systems are a non‐linear function of shunt fraction (Duke et al .…”

“…In this issue of The Journal of Physiology , Stickland et al () conducted a highly technical study involving the combination of three techniques for measuring intracardiac/intrapulmonary shunt in anaesthetized canines. Measurements were made at rest, with dopamine and dobutamine to increase IPAVA recruitment, and finally, with a surgically induced intra‐atrial shunt.…”