J Physiol 586.18 (2008) pp 4559–4565
Hyperoxia prevents exercise-induced intrapulmonary
arteriovenous shunt in healthy humans
Andrew T. Lovering1,2, Michael K. Stickland2, Markus Amann2, Joan C. Murphy2, Matthew J. O’Brien3,
John S. Hokanson4and Marlowe W. Eldridge2,4,5
1Department of Human Physiology, University of Oregon, Eugene, OR, USA
2Department of Population Health Sciences, John Rankin Laboratory of Pulmonary Medicine,3Department of Pulmonary Function,
4Department of Pediatrics, and5Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
The 100% oxygen (O2) technique has been used to detect and quantify right-to-left shunt
for more than 50years. The goal of this study was to determine if breathing 100% O2
affected intrapulmonary arteriovenous pathways during exercise. Seven healthy subjects
(3 females) performed two exercise protocols. In ProtocolI subjects performed an incremental
cycle ergometer test (60W+30W/2min; breathing room air, FIO2=0.209) and arteriovenous
shunting was evaluated using saline contrast echocardiography at each stage. Once significant
as follows: hyperoxia for 180s, normoxia for 120s, hyperoxia for 120s, normoxia for 120s,
hyperoxia for 60s and normoxia for 120s. For ProtocolII, subjects performed an incremental
cycle ergometer test until volitional exhaustion while continuously breathing 100% O2. In
ProtocolI, shunting was seen in all subjects at 120–300W. Breathing oxygen for 1min reduced
resumed upon breathing room air. Similarly, in ProtocolII, breathing 100% O2substantially
decreased or eliminated exercise-induced arteriovenous shunting in all subjects at submaximal
and in 4/7 subjects at maximal exercise intensities. Our results suggest that alveolar hyperoxia
prevents or reduces blood flow through arteriovenous shunt pathways.
(Received 7 July 2008; accepted after revision 31 July 2008; first published online 7 August 2008)
Corresponding author A. T. Lovering: Department of Human Physiology, 1240 University of Oregon, Eugene,
OR 97403-1240, USA. Email: firstname.lastname@example.org
A recent series of studies using anatomically based
approaches to study the pulmonary circulation and
gas exchange during exercise have concluded that
exercise-induced intrapulmonary arteriovenous shunting
via large diameter pathways occurs in healthy humans
and dogs (Eldridge et al. 2004; Stickland et al. 2004,
2007; Lovering et al. 2008). Notwithstanding these
considered to be trivial during exercise in healthy human
subjects (Dempsey & Wagner, 1999).
Breathing 100% O2 would eliminate any diffusion
limitation as well as the contribution of poorly ventilated
alveoli to gas exchange inefficiency making it possible to
quantify venous admixture (Riley & Cournand, 1949).
Accordingly, large diameter arteriovenous pathways that
would channel venous admixture through the lungs,
circumventing the alveoli, should be detected using the
100% O2 technique. However, previous studies using
either the multiple inert gas elimination technique
(MIGET) (Wagner et al. 1986; Hammond et al. 1986)
or the 100% O2technique (Vogiatzis et al. 2008) have
not detected significant intrapulmonary shunting during
have recently shown that reducing alveolar O2 tension
(FIO2=0.12) affects arteriovenous shunt recruitment,
causing shunting to occur at lower absolute exercise
intensities in some subjects and causing shunting to
continue to occur in all subjects breathing hypoxic gas
(FIO2=0.12) for 3–5min post-exercise (Lovering et al.
2008). Thus we hypothesized that high alveolar O2may
modulate arteriovenous pathways in the opposite manner
to low alveolar O2by preventing or eliminating arterio-
C ?2008 The Authors. Journal compilationC ?2008 The Physiological SocietyDOI: 10.1113/jphysiol.2008.159350
J Physiol 586.18
Hyperoxia prevents exercise-induced intrapulmonary shunt4565
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We thank Ms Jensena M. Carlson, Ms Sarah M. Otten, Mrs
Peggy Zingler RRT, Dr Carter Ralphe and Mrs Jaime Beebe
for excellent technical assistance. This work was supported by
T32 HL07654 (A.T.L.), and Grant-In-Aid from the American
Heart Association 0550176Z (M.W.E.) and 0625636Z (M.A.).
M. K. Stickland was supported by the Natural Sciences and
Engineering Council of Canada.
C ?2008 The Authors. Journal compilationC ?2008 The Physiological Society