Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

Melissa L Bates,Marlowe W Eldridge,Joseph E Jacobson

doi:10.3389/fphys.2017.00218

Abstract

Intrapulmonary arteriovenous anastomoses (IPAVA) allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

Highlights

Intrapulmonary arteriovenous anastomoses (IPAVA) directly connect arteries and veins in the lung, thereby bypassing the pulmonary capillary bed (Tobin and Zariquiey, 1950; Tobin, 1966; Lovering et al, 2007)
We found that the addition of exercise, which increases cardiac output, does not increase IPAVA recruitment in hypoxia
We previously used a similar approach to investigate the ability of alveolar hypoxia to recruit IPAVA in intact rats and isolated lungs (Bates et al, 2012)

Summary

Introduction

Intrapulmonary arteriovenous anastomoses (IPAVA) directly connect arteries and veins in the lung, thereby bypassing the pulmonary capillary bed (Tobin and Zariquiey, 1950; Tobin, 1966; Lovering et al, 2007) These pathways, which are ≥70 μm in diameter in the rat (Bates et al, 2012), and are recruited by exercise (Eldridge et al, 2004; Lovering et al, 2006, 2008a,b, 2009; Bates et al, 2014a; Cameron Norris et al, 2014), hypoxia (Lovering et al, 2006; Bates et al, 2012, 2014a), and exogenous catecholamines (Bryan et al, 2012; Laurie et al, 2012; Elliott et al, 2014) in humans. These authors suggest that IPAVA are mechanically recruited by increased cardiac output

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Conclusion