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1 Faculty of Physical Education and Recreation
2 Faculty of Medicine and Dentistry
3 Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada
In young, healthy people the alveolar–arterial PO2 difference (A-aDO2) is small at rest, but frequently increases during exercise. Previously, investigators have focused on ventilation/perfusion mismatch and diffusion abnormalities to explain the impairment in gas exchange, as significant physiological intra-pulmonary shunt has not been found. The aim of this study was to use a non-gas exchange method to determine if anatomical intra-pulmonary (I-P) shunts develop during exercise, and, if so, whether there is a relationship between shunt and increased A-aDO2. Healthy male participants performed graded upright cycling to 90%
while pulmonary arterial (PAP) and pulmonary artery wedge pressures were measured. Blood samples were obtained from the radial artery, cardiac output 
was calculated by the direct Fick method and I-P shunt was determined by administering agitated saline during continuous 2-D echocardiography. A-aDO2 progressively increased with exercise and was related to 
(r
= 0.86) and PAP (r
= 0.75). No evidence of I-P shunt was found at rest in the upright position; however, 7 of 8 subjects developed I-P shunts during exercise. In these subjects, point bi-serial correlations indicated that I-P shunts were related to the increased A-aDO2 (r
= 0.68), 
(r
= 0.76) and PAP (r
= 0.73). During exercise, intra-pulmonary shunt always occurred when A-aDO2 exceeded 12 mmHg and 
was greater than 24 l min–1. These results indicate that anatomical I-P shunts develop during exercise and we suggest that shunt recruitment may contribute to the widened A-aDO2 during exercise.
(Received 31 May 2004;
accepted after revision 16 September 2004;
first published online 23 September 2004)
Corresponding author M. K. Stickland: The John Rankin Laboratory of Pulmonary Medicine, Department of Population Health Sciences, University of Wisconsin School of Medicine, 1300 University Ave, Madison, WI 53706-1532, USA. Email: stickland{at}wisc.edu
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