doi:10.1152/japplphysiol.00693.2009 107:1003, 2009.
J Appl Physiol
Andrew T. Lovering, Marlowe W. Eldridge and Michael K. Stickland
intrapulmonary shunting is imaginary vs. real
Last Word on Point:Counterpoint: Exercise-induced
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Letter To The Editor
Last Word on Point:Counterpoint: Exercise-induced intrapulmonary shunting
is imaginary vs. real
Andrew T. Lovering,1Marlowe W. Eldridge,2and Michael K. Stickland3
1University of Oregon, Department of Human Physiology, Eugene, Oregon;2Department of Population Health Sciences,
Department of Pediatrics, and Department of Biomedical Engineering, University of Wisconsin School of Medicine and
Public Health, John Rankin Laboratory of Pulmonary Medicine, Madison, Wisconsin;3Division of Pulmonary Medicine,
Department of Medicine, University of Alberta, and Centre for Lung Health (Covenant Health), Edmonton, Alberta, Canada
TO THE EDITOR: We thank our colleagues from UCSD for this
enjoyable discourse as well as the additional commentaries
from colleagues around the world. In reviewing the Point:
Counterpoint (3, 5) and the commentaries submitted (see Ref.
4), it appears that there is general agreement that some type of
large-diameter intrapulmonary arteriovenous pathways are re-
cruited with exercise. However, their size, magnitude, regula-
tion, as well as their contribution to pulmonary gas exchange in
health and disease remains to be fully understood. As Dr. Jones
points out (see Ref. 4), comparisons between healthy subjects
who demonstrate a positive contrast echocardiogram vs. those
healthy subjects who do not would add to our understanding of
the significance of these yet unidentified vessels. In reference
to comments made by Dr. Sheel and Dr. Hughes (see Ref. 4),
quantification of intrapulmonary arteriovenous shunt has been
done in dogs (57) and most recently in humans (6); however,
the ability to accurately size these intrapulmonary arterio-
venous pathways in humans is limited because albumin mac-
roaggregates have a variable size distribution, whereas poly-
mer microspheres are of a known and a very specific diameter,
but are not injectable in humans.
Drs. Naeije and Faoro (see Ref. 4) point out that there may
be more plasticity within the pulmonary circulation than pre-
viously assumed and highlight the pulmonary-related compli-
cations associated with chronic liver disease as an example of
this plasticity. In this example, Drs. Naeije and Faoro also
bring attention to the fact that in a pathophysiological condi-
tion, gas exchange-dependent techniques detect a shunt frac-
tion inconsistent with the shunt fraction detected by the ana-
tomic-based methods. It is of interest that observations dating
back more than 30 yr in patients with hemorrhagic hereditary
telangiectasia previously highlighted how “shunt” calculated
anatomically is different than “shunt” determined with gas
exchange techniques (2). With respect to pathophysiology, Dr.
Bates (see Ref. 4) suggests a role for these pathways in both
cardiovascular and pulmonary pathologies, highlighting the
need for further studies of these intrapulmonary arteriovenous
anastomoses in both health and disease.
In summary, with general agreement between all parties, the
next steps will be to 1) determine regulation of these vessels,
2) determine their role in pulmonary gas exchange in health
and disease, 3) better quantify magnitude of vessel blood flow,
and 4) establish anatomic origin of these vessels. Undoubtedly
the role of the Journal of Applied Physiology’s Point:Counter-
point is to search for truth within controversies that exist in
physiology at present so that our understanding will evolve.
Our colleagues at UCSD suggested that our shunts are much
like Horton’s Whos, small and insignificant, leaving the reader
to decide if they should even care about this controversy, while
explanations for pulmonary gas exchange efficiency during
exercise remain unresolved. In keeping with the spirit of this
Point:Counterpoint, we would be remiss to not include a final
closing quotation from Dr. Seuss, which we feel sums up the
collective interest of ourselves and our colleagues regarding
the area of pulmonary gas exchange, pulmonary circulation,
and exercise: “Unless someone like you cares a whole awful
lot, nothing is going to get better. It’s not. (1)”
This work was supported by the American Heart Association Scientist
Development Grant SDG2280238 (to A. T. Lovering), American Heart Asso-
ciation Grant-In-Aid 0550176Z (to M. W. Eldridge), and Canadian Institutes of
Health Research New Investigator Award (to M. K. Stickland).
1. Geisel TS. The Lorax. New York City: Random House, 1971.
2. Genovesi MG, Tierney DF, Taplin GV, Eisenberg H. An intravenous
radionuclide method to evaluate hypoxemia caused by abnormal alveolar
vessels. Limitation of conventional techniques. Am Rev Respir Dis 114:
3. Hopkins SR, Olfert IM, Wagner PD, Lovering AT, Eldridge MW,
Stickland MK. Point: Exercise-induced intrapulmonary shunting is imag-
inary. J Appl Physiol; doi:10.1152/japplphysiol.91489.2008.
4. Jones RL, Sheel AW, Naeije R, Faoro V, Hughes JM, Bates ML.
Comments on Point:Counterpoint: Exercise-induced intrapulmonary shunt-
ing is imaginary vs. real. J Appl Physiol; doi:10.1152/japplphysiol.00660.
5. Lovering AT, Eldridge MW, Stickland MK. Counterpoint: Exercise-
induced intrapulmonary shunting is real. J Appl Physiol; doi:10.1152/
6. Lovering AT, Haverkamp HC, Romer LM, Hokanson JS, Eldridge
MW. Transpulmonary passage of
healthy humans at rest and during maximal exercise. J Appl Physiol 106:
7. Stickland MK, Lovering AT, Eldridge MW. Exercise-induced arterio-
venous intrapulmonary shunting in dogs. Am J Respir Crit Care Med 176:
99mTc macroaggregated albumin in
Address for reprint requests and other correspondence: A. T. Lovering,
Dept. of Human Physiology, 1240 Univ. of Oregon, Eugene, OR 97403-1240
J Appl Physiol 107: 1003, 2009;
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on May 21, 2011