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The pulmonary vasculature during exercise in health and mild chronic obstructive pulmonary disease Open Access

Descriptions

Other title
Subject/Keyword
Pulmonary gas exchange
Intrapulmonary arteriovenous anastomosis
Pulmonary Vasculature
Intrapulmonary shunt
Chronic obstructive pulmonary disease
Dopamine
Dyspnea
Exercise
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Tedjasaputra, Vincent
Supervisor and department
Stickland, Michael (Medicine and Dentistry)
Examining committee member and department
Welsh, Robert (Medicine and Dentistry)
Sheel, William (Kinesiology, University of British Columbia)
Petersen, Stewart (Physical Education and Recreation)
Jensen, Dennis (Kinesiology, McGill University)
Department
Physical Education and Recreation
Specialization

Date accepted
2017-06-22T08:28:46Z
Graduation date
2017-11:Fall 2017
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
The purpose of this dissertation was to characterize the response of the pulmonary vasculature to exercise in health (including a pharmacological intervention) and in individuals with mild chronic obstructive lung disease. The first project studied the effect of a dopamine receptor blockade on the gas exchange response during exercise in 12 healthy males (age: 25 ± 6 years, V̇ O2max = 58.6 ± 6.5 mL.kg-1.min-1). Previous research has demonstrated recruitment of Intrapulmonary (IP) shunt during exercise, which may contribute to gas exchange impairment. IP shunts are recruited with dopamine infusion and endogenous dopamine increases with exercise intensity. It was hypothesized that dopamine receptor blockade would reduce the recruitment of IP shunt during exercise and reduce gas exchange impairment. Administration of 20 mg metoclopramide did not reduce IP shunt recruitment, as assessed by agitated saline contrast echocardiography. However, the alveolar-arterial oxygen difference was reduced by 23%, and increased arterial oxygen saturation by 0.8% during exercise at 85% of V̇ O2max, indicating an improvement in gas exchange impairment. Also, dopamine receptor blockade reduced peak oxygen consumption by 5.5% and time-to-exhaustion while exercising at 90% of V̇ O2max by 38.6%. As dopamine is a known pulmonary vasodilator, this study suggests that endogenous dopamine is important to the normal cardiopulmonary response to exercise, and is necessary for optimal high-intensity exercise performance. The purpose of this dissertation was to characterize the response of the pulmonary vasculature to exercise in health (including a pharmacological intervention) and in individuals with mild chronic obstructive lung disease. The first project studied the effect of a dopamine receptor blockade on the gas exchange response during exercise in 12 healthy males (age: 25 ± 6 years, V̇O2max = 58.6 ± 6.5 mL.kg-1.min-1). Previous research has demonstrated recruitment of Intrapulmonary (IP) shunt during exercise, which may contribute to gas exchange impairment. IP shunts are recruited with dopamine infusion and endogenous dopamine increases with exercise intensity. It was hypothesized that dopamine receptor blockade would reduce the recruitment of IP shunt during exercise and reduce gas exchange impairment. Administration of 20 mg metoclopramide did not reduce IP shunt recruitment, as assessed by agitated saline contrast echocardiography. However, the alveolar-arterial oxygen difference was reduced by 23%, and increased arterial oxygen saturation by 0.8% during exercise at 85% of V̇O2max, indicating an improvement in gas exchange impairment. Also, dopamine receptor blockade reduced peak oxygen consumption by 5.5% and time-to-exhaustion while exercising at 90% of V̇O2max by 38.6%. As dopamine is a known pulmonary vasodilator, this study suggests that endogenous dopamine is important to the normal cardiopulmonary response to exercise, and is necessary for optimal high-intensity exercise performance. Two subsequent projects examined the relative contributions of pulmonary capillary blood volume (Vc) and membrane diffusing capacity (Dm) to the overall increase in diffusing capacity (DLCO) during exercise. Endurance-trained athletes exhibit enhanced cardiovascular function compared to sedentary non-athletes, but it is accepted that exercise training does not enhance lung structure and function. The second study investigated differences between 15 endurance-trained athletes (V̇O2max = 64.6 ± 6.9 mL.kg-1.min-1) and 14 age- and height-matched sedentary controls (V̇O2max = 45.0 ± 4.4 mL.kg-1.min-1). We found that athletes had 15% greater DLCO during exercise at 90% of V̇O2max, secondary to 30% greater Dm compared to sedentary controls. No difference in pulmonary capillary blood volume (Vc) was observed. These data suggest that athletes appear to have an enhanced pulmonary membrane that facilitates the increased oxygen uptake during high-level exercise. The third project examined the DLCO response to exercise in mild chronic obstructive pulmonary disease (COPD). Previous research has shown that mild COPD patients exhibit pulmonary vascular impairment, indicating that the impact of the disease is worse than spirometry testing would suggest. We recruited 15 mild COPD (FEV1/FVC = 64 ± 3, FEV1 = 93 ± 13% of predicted) and 15 height-, sex-, and age-matched controls, and measured DLCO, Vc, and Dm at rest and during exercise. We observed 22% lower DLCO at rest and during exercise in mild COPD, which is primarily caused by 24% lower capillary blood volume. No difference in membrane diffusing capacity was observed between groups. These results suggest that, despite the relatively minor airway obstruction, individuals with mild COPD exhibit some pulmonary vascular impairment that precedes changes to the alveolar interface, such as emphysema. Together, this dissertation contributes to the understanding of the importance of the pulmonary vasculature to cardiovascular function and pulmonary gas exchange during exercise in health and mild chronic obstructive lung disease. lung structure and function. The second study investigated differences between 15 endurance- ii trained athletes (V̇ O2max = 64.6 ± 6.9 mL.kg-1.min-1) and 14 age- and height-matched sedentary controls (V̇ O2max = 45.0 ± 4.4 mL.kg-1.min-1). We found that athletes had 15% greater DLCO during exercise at 90% of V̇ O2max, secondary to 30% greater Dm compared to sedentary controls. No difference in pulmonary capillary blood volume (Vc) was observed. These data suggest that athletes appear to have an enhanced pulmonary membrane that facilitates the increased oxygen uptake during high-level exercise. The third project examined the DLCO response to exercise in mild chronic obstructive pulmonary disease (COPD). Previous research has shown that mild COPD patients exhibit pulmonary vascular impairment, indicating that the impact of the disease is worse than spirometry testing would suggest. We recruited 15 mild COPD (FEV1/FVC = 64 ± 3, FEV1 = 93 ± 13% of predicted) and 15 height-, sex-, and age-matched controls, and measured DLCO, Vc, and Dm at rest and during exercise. We observed 22% lower DLCO at rest and during exercise in mild COPD, which is primarily caused by 24% lower capillary blood volume. No difference in membrane diffusing capacity was observed between groups. These results suggest that, despite the relatively minor airway obstruction, individuals with mild COPD exhibit some pulmonary vascular impairment that precedes changes to the alveolar interface, such as emphysema. Together, this dissertation contributes to the understanding of the importance of the pulmonary vasculature to cardiovascular function and pulmonary gas exchange during exercise in health and mild chronic obstructive lung disease.
Language
English
DOI
doi:10.7939/R3513V895
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Tedjasaputra V, Bryan TL, van Diepen S, Moore LE, Bouwsema MM, Welsh RC, Petersen SR, Stickland MK (2015). Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise performance in healthy humans. J Physiol 593, 3147–3157.Tedjasaputra V, Bouwsema MM, Stickland MK. (2016). Effect of aerobic fitness on capillary blood volume and diffusing membrane capacity responses to exercise. J Physiol 594, 4359–4370.

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