Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

Micah W. Johnson; Bryan J. Taylor; Minelle L. Hulsebus; Bruce D. Johnson; Eric M. Snyder

doi:10.1016/j.resp.2012.06.004

Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

Micah W. Johnson, Bryan J. Taylor, Minelle L. Hulsebus, Bruce D. Johnson, Eric M. Snyder

Kinesiology

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7 Scopus citations

Abstract

Background: Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β₂AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β₂AR density on lymphocytes and indices of lung water in healthy humans exposed to ~17h of hypoxia (FIO2=12.5% in a hypoxia tent). Methods: Thirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m², VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (V_tis-tissue, blood and water), lung diffusing capacity for carbon monoxide (D_CO) and nitric oxide (D_NO), alveolar-capillary conductance (D_M), pulmonary capillary blood volume (V_c) and lung water (CT V_tis-V_c) were assessed before and after ~17h normobaric hypoxia (FIO2=12.5%). β₂AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. Results: After 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. V_c and D_M both increased with hypoxia with a small increase in D_M/V_c ratio (p>0.05). CT V_tis decreased and lung water was estimated to decline 7±13%, respectively. β₂AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β₂AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. Conclusions: Lung water decreases with 17. h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.

Original language	English (US)
Pages (from-to)	159-165
Number of pages	7
Journal	Respiratory Physiology and Neurobiology
Volume	183
Issue number	2
DOIs	https://doi.org/10.1016/j.resp.2012.06.004
State	Published - Aug 15 2012

Bibliographical note

Funding Information:
This work was supported by NIH grant HL71478 . We would like to thank Kathy O’Malley, for her help with data collection and Renee Blumers for her help with manuscript preparation as well as the efforts of the study participants. We would also like to thank the staff of the Center for Translational Sciences Activities (CTSA) for their assistance throughout this study. The Mayo Clinic CTSA is supported by US Public Health Service grant M01-RR00585 .

Keywords

Altitude physiology
Edema
Lung water
Pulmonary congestion

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@article{da2f1ae7db984fb49db85f8ad19d6e5c,

title = "Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes",

abstract = "Background: Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β2AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β2AR density on lymphocytes and indices of lung water in healthy humans exposed to ~17h of hypoxia (FIO2=12.5% in a hypoxia tent). Methods: Thirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m2, VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (Vtis-tissue, blood and water), lung diffusing capacity for carbon monoxide (DCO) and nitric oxide (DNO), alveolar-capillary conductance (DM), pulmonary capillary blood volume (Vc) and lung water (CT Vtis-Vc) were assessed before and after ~17h normobaric hypoxia (FIO2=12.5%). β2AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. Results: After 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. Vc and DM both increased with hypoxia with a small increase in DM/Vc ratio (p>0.05). CT Vtis decreased and lung water was estimated to decline 7±13%, respectively. β2AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β2AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. Conclusions: Lung water decreases with 17. h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.",

keywords = "Altitude physiology, Edema, Lung water, Pulmonary congestion",

author = "Johnson, {Micah W.} and Taylor, {Bryan J.} and Hulsebus, {Minelle L.} and Johnson, {Bruce D.} and Snyder, {Eric M.}",

note = "Funding Information: This work was supported by NIH grant HL71478 . We would like to thank Kathy O{\textquoteright}Malley, for her help with data collection and Renee Blumers for her help with manuscript preparation as well as the efforts of the study participants. We would also like to thank the staff of the Center for Translational Sciences Activities (CTSA) for their assistance throughout this study. The Mayo Clinic CTSA is supported by US Public Health Service grant M01-RR00585 .",

year = "2012",

month = aug,

day = "15",

doi = "10.1016/j.resp.2012.06.004",

language = "English (US)",

volume = "183",

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T1 - Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

AU - Johnson, Micah W.

AU - Taylor, Bryan J.

AU - Hulsebus, Minelle L.

AU - Johnson, Bruce D.

AU - Snyder, Eric M.

N1 - Funding Information: This work was supported by NIH grant HL71478 . We would like to thank Kathy O’Malley, for her help with data collection and Renee Blumers for her help with manuscript preparation as well as the efforts of the study participants. We would also like to thank the staff of the Center for Translational Sciences Activities (CTSA) for their assistance throughout this study. The Mayo Clinic CTSA is supported by US Public Health Service grant M01-RR00585 .

PY - 2012/8/15

Y1 - 2012/8/15

N2 - Background: Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β2AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β2AR density on lymphocytes and indices of lung water in healthy humans exposed to ~17h of hypoxia (FIO2=12.5% in a hypoxia tent). Methods: Thirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m2, VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (Vtis-tissue, blood and water), lung diffusing capacity for carbon monoxide (DCO) and nitric oxide (DNO), alveolar-capillary conductance (DM), pulmonary capillary blood volume (Vc) and lung water (CT Vtis-Vc) were assessed before and after ~17h normobaric hypoxia (FIO2=12.5%). β2AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. Results: After 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. Vc and DM both increased with hypoxia with a small increase in DM/Vc ratio (p>0.05). CT Vtis decreased and lung water was estimated to decline 7±13%, respectively. β2AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β2AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. Conclusions: Lung water decreases with 17. h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.

AB - Background: Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β2AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β2AR density on lymphocytes and indices of lung water in healthy humans exposed to ~17h of hypoxia (FIO2=12.5% in a hypoxia tent). Methods: Thirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m2, VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (Vtis-tissue, blood and water), lung diffusing capacity for carbon monoxide (DCO) and nitric oxide (DNO), alveolar-capillary conductance (DM), pulmonary capillary blood volume (Vc) and lung water (CT Vtis-Vc) were assessed before and after ~17h normobaric hypoxia (FIO2=12.5%). β2AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. Results: After 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. Vc and DM both increased with hypoxia with a small increase in DM/Vc ratio (p>0.05). CT Vtis decreased and lung water was estimated to decline 7±13%, respectively. β2AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β2AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. Conclusions: Lung water decreases with 17. h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.

KW - Altitude physiology

KW - Edema

KW - Lung water

KW - Pulmonary congestion

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Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

Abstract

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