Lung Fluid Balance in Humans: Impact of hypoxia & the β₂ Adrenergic Receptor

 

Bruce D. Johnson

Mayo Clinic, Rochester, MN

 

Lung fluid regulation plays an important role in the pathophysiology of a number of conditions, including the pulmonary edema associated with high altitude exposure as well as in clinical conditions such as heart failure.  Mechanisms of fluid regulation are complex and include a balance between factors influencing lung fluid accumulation and removal.  Changes in lung fluid balance are difficult to measure noninvasively in humans.  In this presentation we examine techniques to assess alterations in lung fluid balance in humans (using CT imaging and measures of alveolar-capillary conductance), determine the sensitivity of these measures to quantify changes with rapid intravenous fluid loading (30 ml/kg saline over 15 minutes) and then examine the impact of 18 hours normobaric hypoxia on lung fluid regulation in 25 healthy adults (age 30±8 yr). In addition we examine the role of an inhaled beta 2 adrenergic receptor (β₂AR) agonist on measures of alveolar-capillary conductance in healthy adults and the potential role that variation in the gene that encodes this receptor may have on lung fluid accumulation during rapid fluid loading and with normobaric hypoxic exposure.  Additional studies are being pursued to determine the role of genetic variation in the beta 2 adrenergic receptor on lung fluid regulation in the heart failure population.

 

Key Words: lung water, edema, altitude, genotype, catecholamines