Effect of initial gas bubble composition on detection of inducible intrapulmonary arteriovenous shunt during exercise in normoxia, hypoxia, or hyperoxia

Abstract

Concern has been raised that altering the fraction of inspired O₂ (Fi(O₂)) could accelerate or decelerate microbubble dissolution time within the pulmonary vasculature and thereby invalidate the ability of saline contrast echocardiography to detect intrapulmonary arteriovenous shunt in subjects breathing either a low or a high Fi(O₂). The present study determined whether the gaseous component used for saline contrast echocardiography affects the detection of exercise-induced intrapulmonary arteriovenous shunt under varying Fi(O₂). Twelve healthy human subjects (6 men, 6 women) performed three 11-min bouts of cycle ergometer exercise at 60% peak O₂ consumption (Vo(2peak)) in normoxia, hypoxia (Fi(O₂) = 0.14), and hyperoxia (Fi(O₂) = 1.0). Five different gases were used to create saline contrast microbubbles by two separate methods and were injected intravenously in the following order at 2-min intervals: room air, 100% N₂, 100% O₂, 100% CO₂, and 100% He. Breathing hyperoxia prevented exercise-induced intrapulmonary arteriovenous shunt, whereas breathing hypoxia and normoxia resulted in a significant level of exercise-induced intrapulmonary arteriovenous shunt. During exercise, for any Fi(O₂) there was no significant difference in bubble score when the different microbubble gas compositions made with either method were used. The present results support our previous work using saline contrast echocardiography and validate the use of room air as an acceptable gaseous component for use with saline contrast echocardiography to detect intrapulmonary arteriovenous shunt during exercise or at rest with subjects breathing any Fi(O₂). These results suggest that in vivo gas bubbles are less susceptible to changes in the ambient external environment than previously suspected.

Detection of Intracardiac and Intrapulmonary Shunts at Rest and During Exercise Using Saline Contrast Echocardiography

“…A disadvantage is that it can be difficult to image a patient during exercise in this position if they have abdominal obesity. To date, similar results have been found when comparing right-to-left shunt during recumbent and upright exercise (Stickland et al, 2004;La Gerche et al, 2010;Elliott et al, 2011a). There are no published data examining intrapulmonary shunting during supine exercise.…”

“…Typically, 0.5-1 ml of air and 4-10 ml of saline are used to manually agitate between two syringes connected by stopcocks for a total injection volume of 10 ml (Otto, 2004;Feigenbaum, 2005;Woods et al, 2010). In a research setting, equal success has been achieved in detecting right-to-left shunts via intrapulmonary arteriovenous anastomoses using 0.5-1 ml of air and 3-5 ml of saline, for a total injection volume of 5 ml (Stickland & Lovering, 2006;Laurie et al, 2010;Lovering et al, 2010;Elliott et al, 2011a). The agitated saline mix solution should be injected as a bolus, forcibly by hand.…”

“…The second injection should confirm the presence of an intracardiac shunt if there is increased contrast and/or if the contrast bubbles continue to appear in the left heart in ≤ 3 heartbeats. Alternatively, if saline contrast bubbles appear in the left heart in > 3 heartbeats after their appearance in the right heart, then an intrapulmonary shunt is suspected, e.g., pulmonary arteriovenous malformation, pulmonary arteriovenous anastomoses (Nanthakumar et al, 2001;Lee et al, 2003;van Gent et al, 2009;Elliott et al, 2011a). The different types of intracardiac and intrapulmonary shunts are outlined in detail below.…”

“…We have considerable experience successfully performing diagnostic contrast-enhanced spectral Doppler studies during exercise and evaluations of right-to-left shunting during exercise on subjects in the forward-leaning upright bike arrangement, or "Aerobar" position (Lovering et al, 2008b;Elliott et al, 2011a) (Figure 3). The "Aerobar" position has several advantages: One, subjects are able to lean forward resting their forearms on bars that allow them to maintain a relatively still upper body during exercise.…”

“…They are also specifically contraindicated for use when there is a known or suspected intracardiac shunt (Mulvagh et al, 2008). It has been demonstrated that exercise opens intrapulmonary arteriovenous anastomoses that were closed at rest in healthy humans (Eldridge et al, 2004;Stickland et al, 2004;La Gerche et al, 2010;Elliott et al, 2011a). Furthermore, increasing exercise intensity increases the amount of saline contrast that is detected in the left ventricle, which is indicative of increased intrapulmonary shunting (Stickland et al, 2004).…”