Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude

Abstract

What is the central question of this study? The aim was to determine, using the technique of agitated saline contrast echocardiography, whether exercise after 4-7 days at 5050 m would affect blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) compared with exercise at sea level. What is the main finding and its importance? Despite a significant increase in both cardiac output and pulmonary pressure during exercise at high altitude, there is very little Q̇IPAVA at rest or during exercise after 4-7 days of acclimatization. Mathematical modelling suggests that bubble instability at high altitude is an unlikely explanation for the reduced Q̇IPAVA. Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) is elevated during exercise at sea level (SL) and at rest in acute normobaric hypoxia. After high altitude (HA) acclimatization, resting Q̇IPAVA is similar to that at SL, but it is unknown whether this is true during exercise at HA. We reasoned that exercise at HA (5050 m) would exacerbate Q̇IPAVA as a result of heightened pulmonary arterial pressure. Using a supine cycle ergometer, seven healthy adults free from intracardiac shunts underwent an incremental exercise test at SL [25, 50 and 75% of SL peak oxygen consumption (V̇O2 peak )] and at HA (25 and 50% of SL V̇O2 peak ). Echocardiography was used to determine cardiac output (Q̇) and pulmonary artery systolic pressure (PASP), and agitated saline contrast was used to determine Q̇IPAVA (bubble score; 0-5). The principal findings were as follows: (i) Q̇ was similar at SL rest (3.9 ± 0.47 l min ) compared with HA rest (4.5 ± 0.49 l min ; P = 0.382), but increased from rest during both SL and HA exercise (P < 0.001); (ii) PASP increased from SL rest (19.2 ± 0.7 mmHg) to HA rest (33.7 ± 2.8 mmHg; P = 0.001) and, compared with SL, PASP was further elevated during HA exercise (P = 0.003); (iii) Q̇IPAVA was increased from SL rest (0) to HA rest (median = 1; P = 0.04) and increased from resting values during SL exercise (P < 0.05), but was unchanged during HA exercise (P = 0.91), despite significant increases in Q̇ and PASP. Theoretical modelling of microbubble dissolution suggests that the lack of Q̇IPAVA in response to exercise at HA is unlikely to be caused by saline contrast instability.

High adventure shunts old notions of pulmonary vascular control during hypoxic exercise: contrasting views that might just burst your bubble!

“…Although blood flow through arteriovenous circuits is generally regarded as negligible at rest in healthy humans, it increases during exercise in an intensity-dependent manner (Eldridge et al 2004) when, amongst other things, cardiac output and pulmonary artery pressure both increase. Subject heart rate, estimated oxygen saturation, cardiac output and pulmonary artery systolic pressure were determined at rest and during incremental workloads to 25, 50 and 75% of peak oxygen consumption at sea level and to 25 and 50% of the sea-level peak oxygen consumption at high altitude.Consistent with previous studies, Boulet et al (2017) report no apparent flow through lung anastomoses in healthy subjects at sea level during rest, but bubble scores were increased as a function of exercise intensity, confirming the recruitment of arteriovenous shunts. Alveolar bypass by way of exercise-induced recruitment of intrapulmonary arteriovenous conduits could detract from efficient gas exchange, potentially contributing to a widening of alveolar-arterial P O2 difference during exercise (Stickland et al 2007), notwithstanding the possibility that potential deficits could be offset by separate exercise-induced events and lack of evidence of right-to-left physiological shunt during exercise in several studies using assessments of gas exchange.…”

“…Consistent with previous studies, Boulet et al (2017) report no apparent flow through lung anastomoses in healthy subjects at sea level during rest, but bubble scores were increased as a function of exercise intensity, confirming the recruitment of arteriovenous shunts. In the same healthy subjects acclimatized for 4-7 days at 5050 m (after a 10-12 day hike to the Pyramid laboratory from Lukla), there was a small increase in bubble score in some subjects at rest.…”

“…Arteriovenous anastomoses in mammalian lungs can serve as low-resistance short circulatory routes that bypass the business end of gas exchange. Until now, the impact of exercise on intrapulmonary vascular shunt in lowlander lungs at high altitude was unknown.In this issue of Experimental Physiology, Boulet et al (2017) tackle the tricky task with a spirit of great adventure, performing contrast echocardiography in healthy subjects during recumbent cycle ergometry at the Ev-K2-CNR Pyramid Laboratory in Nepal at 5050 m, after baseline assessments performed at 'sea level' (Kelowna, British Columbia, Canada; 344 m). Intrapulmonary vascular shunt is also increased by the administration of cardiac inotropes.…”

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

“…; Boulet et al . ). Finally, the multiple inert gas elimination technique (MIGET) provides an assessment of gas exchange through the infusion of six inert gases of varying blood solubilities.…”

“…; Boulet et al . ). Technical improvement in how agitated saline contrast detection is quantified is clearly required to improve its specificity.…”